Johan Øvrevik

• Barth, Alexandre; Utinger, Battist; He, Quanfu; Paul, Andreas; Hartikainen, Anni & Ihalainen, Mika [Vis alle 24 forfattere av denne artikkelen] (2026). Online characterisation of oxidative potential and reactive oxygen species of fresh and aged aircraft turbine and ship engine particulate emissions. Environmental Science: Atmospheres. ISSN 2634-3606. doi: 10.1039/d5ea00174a. Fulltekst i vitenarkiv
• Kokkola, Tuukka; Sipkens, Timothy A.; Paul, Andreas; Shukla, Deeksha; Ihalainen, Mika & Das, Anusmita [Vis alle 25 forfattere av denne artikkelen] (2026). Highly light-absorbing particle emissions from low-sulfur marine fuels. npj Climate and Atmospheric Science. 9(1). doi: 10.1038/s41612-026-01369-w. Fulltekst i vitenarkiv
• Shukla, Deeksha; Czech, Hendryk; Kokkola, Tuukka; Bauer, Martin; Paul, Andreas & Etzien, Uwe [Vis alle 18 forfattere av denne artikkelen] (2025). Emission speciation of volatile and intermediate volatility organic compounds from a marine engine: effect of engine load, fuel type and photochemical aging. Environmental Science: Atmospheres. ISSN 2634-3606. 5(9), s. 973–986. doi: 10.1039/d5ea00040h. Fulltekst i vitenarkiv
• Hartikainen, Anni; Ihalainen, Mika; Shukla, Deeksha; Rohkamp, Marius; Mukherjee, Arya & He, Quanfu [Vis alle 30 forfattere av denne artikkelen] (2025). Photochemical aging of aviation emissions: transformation of chemical and physical properties of exhaust emissions from a laboratory-scale jet engine combustion chamber. Atmospheric Chemistry and Physics (ACP). ISSN 1680-7316. 25(16), s. 9275–9294. doi: 10.5194/acp-25-9275-2025. Fulltekst i vitenarkiv
• Helleve, Arnfinn; Gregório, Maria João; Bergsvik, Daniel; Bølling, Anette Kocbach; Cosmi, Valentina De & Fras, Neza [Vis alle 18 forfattere av denne artikkelen] (2025). Strengthening the use of regulatory policy measures for prevention of NCDs in Europe through the JA PreventNCD project. Scandinavian Journal of Public Health. ISSN 1403-4948. 53(Suppl. 3), s. 27–34. doi: 10.1177/14034948251374402. Fulltekst i vitenarkiv Vis sammendrag

  Aims: The Joint Action project on Cancer and other Non-communicable Diseases (NCDs) prevention, Action on Health Determinants, includes a dedicated workstream on structural and population-level interventions. The overarching objective of this workstream is to strengthen the compliance, coherence, implementation and enforcement of evidence-based regulatory measures that support governmental efforts to reduce the burden of NCDs. Methods: The workstream adopts a multi-method approach, informed by existing academic literature and previous European studies. Key methodologies include policy mapping, evidence reviews, behavioural assessments, policy impact modelling, and pilot testing. Governmental alcohol and tobacco policies will be evaluated using comparative policy scales, while the health and economic impacts of health taxation policies will be projected through and microsimulation modelling. Nutrient profile modelling and food composition databases will be developed to inform strategies for food reformulation. The effectiveness of labelling interventions will be examined. Tools for monitoring digital marketing exposure will be developed, and the impact of environmental policy impact will be assessed. Expected results: The workstream is expected to deliver comprehensive policy analyses, demonstrate the potential impact of health taxation, propose harmonized nutrient profiling frameworks, assess the effectiveness of food and alcohol labelling practices and contribute to the development of cross-national structures for public food procurement. Additionally, it will provide guidance on the implementation of effective measures and evaluate divergences in national policy approaches across Europe. Conclusions: The workstream will generate actionable evidence and documentation to inform and support public policy processes, thereby contributing to reductions in the burden of preventable disease across the region.

• Gunasingam, Gowsinth; He, Ruiwen; Fortunatus, Roman M.; Larios, Jorge; Almeida, Mauro Sousa de & Balog, Sandor [Vis alle 9 forfattere av denne artikkelen] (2025). Interplay between lung and intestine in responses to diesel exhaust particles: Contrasting intestinal effects of cleared and swallowed particles with lung-mediated effects using an in vitro approach. Environmental Pollution (1987). ISSN 0269-7491. 389. doi: 10.1016/j.envpol.2025.127399. Fulltekst i vitenarkiv
• Grytting, Vegard Sæter; Kirkerød, Elisabeth; Skuland, Tonje Schwach; Refsnes, Magne Arnold; Låg, Marit & Sadiktsis, Ioannis [Vis alle 9 forfattere av denne artikkelen] (2025). Pro-inflammatory effects of road wear particles and diesel exhaust particles in bronchial epithelial cells and macrophages. Environmental Research. ISSN 0013-9351. 283. doi: 10.1016/j.envres.2025.122134. Fulltekst i vitenarkiv
• Låg, Marit; Skuland, Tonje Schwach; Ballangby, Jarle; Grytting, Vegard Sæter; Jørgensen, Rikke Bramming & Snilsberg, Brynhild [Vis alle 9 forfattere av denne artikkelen] (2025). Mechanisms involved in pro-inflammatory responses to traffic-derived particulate matter (PM) in THP-1 macrophages compared to HBEC3-KT bronchial epithelial cells. Toxicology. ISSN 0300-483X. 516, s. 1–18. doi: 10.1016/j.tox.2025.154174. Fulltekst i vitenarkiv Vis sammendrag

  The pro-inflammatory responses in THP-1-derived macrophages and human bronchial epithelial cells (HBEC3-KT) were examined after exposure to size-fractioned particulate matter (PM) sampled in two road tunnels. All tunnel PM samples induced release and expression of CXCL8 and IL-1β in THP-1 macrophages (50 µg/mL) and HBEC3-KT cells (100 µg/mL), but the potency of the samples differed between the cell types. The road tunnel PM induced pro-inflammatory responses in the macrophages to a much higher extent than diesel exhaust particles (DEP) and particles derived from the stone materials used in the asphalt. Tunnel PM induced a markedly higher increase in cytochrome P450 (CYP)1A1 expression in HBEC3-KT cells than in THP-1 macrophages. The content of organic carbon (OC) in PM correlated to the release of CXCL8 in HBEC3-KT cells, but not in THP-1 macrophages. Moreover, the aryl hydrocarbon receptor (AhR)-inhibitor CH223191 and the antioxidant N-acetyl cysteine (NAC) reduced the PM-induced cytokine release in the macrophages to a lower extent than in HBEC3-KT. In contrast, a toll-like receptor (TLR)2 antibody markedly reduced the PM-induced responses in THP-1 macrophages, but not in HBEC3-KT. A TLR4 antibody was without effect in both cell types. The levels of the microbial TLR2-ligand β-glucan in the PM samples were in a range that might be sufficient to induce pro-inflammatory responses. However, a microbial-independent mechanism could also be involved. In support of such a mechanism, the pro-inflammatory responses to a sample of α-quartz (Min-U-Sil 5), with low levels of β-glucan, were reduced by anti-TLR2. In conclusion, our results indicate that traffic-derived PM exert pro-inflammatory responses in THP-1 macrophages and HBEC3-KT cells via different PM constituents and mechanisms. OC/AhR-dependent mechanisms appeared to be important for PM-induced CXCL8 responses in HBEC3-KT cells, while the cytokine responses in THP-1 macrophages seemed to involve TLR2-mediated activation, either via β-glucan-dependent or -independent mechanisms.

• Bergman, Åke; Jörundsdóttir, Hrönn; Knudsen, Lisbeth E.; Viluksela, Matti; Alexander, Jan & Krøkje, Aase [Vis alle 17 forfattere av denne artikkelen] (2025). Chemical risk analysis competence in the Nordics is at stake. Environmental Science and Pollution Research. ISSN 0944-1344. doi: 10.1007/s11356-025-36318-2. Fulltekst i vitenarkiv
• Rao-Skirbekk, Shilpa; Gutzkow, Kristine Bjerve; Hyllestad, Susanne; Jore, Solveig; Thomsen, Cathrine & Andersen, Gro Dehli [Vis alle 16 forfattere av denne artikkelen] (2025). Climate change and health in the Arctic. Scandinavian Journal of Public Health. ISSN 1403-4948. 53(2), s. 207–214. doi: 10.1177/14034948241296309. Fulltekst i vitenarkiv
• Grytting, Vegard Sæter; Skuland, Tonje Schwach; Ballangby, Jarle; Refsnes, Magne Arnold; Låg, Marit & Øvrevik, Johan [Vis alle 7 forfattere av denne artikkelen] (2024). The effects of fine particulate matter (SRM 2786) on three different 3D lung models exposed at the air-liquid interface – A comparative study. Toxicology in Vitro. ISSN 0887-2333. 98. doi: 10.1016/j.tiv.2024.105841. Fulltekst i vitenarkiv Vis sammendrag

  3D cell culture models exposed at the air-liquid interface (ALI) represent a potential alternative to animal experiments for hazard and risk assessment of inhaled compounds. This study compares cocultures composed of either Calu-3, A549 or HBEC3-KT lung epithelial cells, cultured together with THP-1-derived macrophages and EA.hy926 endothelial cells, in terms of barrier capacity and responses to a standard reference sample of fine particulate matter (SRM 2786). High-content imaging analysis revealed a similar cellular composition between the different cell models. The 3D cell cultures with Calu-3 cells showed the greatest barrier capacity, as measured by transepithelial electrical resistance and permeability to Na-fluorescein. Mucus production was detected in 3D cell cultures based on Calu-3 and A549 cells. Exposure to SRM 2786 at ALI increased cytokine release and expression of genes associated with inflammation and xenobiotic metabolism. Moreover, the presence of THP-1-derived macrophages was central to the cytokine responses in all cell models. While the different 3D cell culture models produced qualitatively similar responses, more pronounced pro-inflammatory responses were observed in the basolateral compartment of the A549 and HBEC3-KT models compared to the Calu-3 model, likely due to their reduced barrier capacity and lower retention of secreted mediators in the apical compartment.

• Rao-Skirbekk, Shilpa; Gützkow, Kristine Bjerve; Hyllestad, Susanne; Jore, Solveig; Thomsen, Cathrine & Andersen, Gro Dehli [Vis alle 16 forfattere av denne artikkelen] (2024). Climate Change and Health in the Arctic. I Butler, Colin D. & Higgs, Kerryn (Red.), Climate Change and Global Health : Primary, Secondary and Tertiary Effects. CABI Publishing. ISSN 9781800620001. s. 462–472. doi: 10.1079/9781800620025.0037. Fulltekst i vitenarkiv
• Holme, Jørn Andreas; Myhre, Oddvar & Øvrevik, Johan (2024). Adverse neurodevelopment in children associated with prenatal exposure to fine particulate matter (PM2.5) – Possible roles of polycyclic aromatic hydrocarbons (PAHs) and mechanisms involved. Reproductive Toxicology. ISSN 0890-6238. 130. doi: 10.1016/j.reprotox.2024.108718. Fulltekst i vitenarkiv Vis sammendrag

  Prenatal exposure to ambient fine particles (PM2.5) and polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse birth outcomes including neurodevelopmental effects with cognitive and/or behavioral implications in early childhood. As a background we first briefly summarize human studies on PM2.5 and PAHs associated with adverse birth outcomes and modified neurodevelopment. Next, we add more specific information from animal studies and in vitro studies and elucidate possible biological mechanisms. More specifically we focus on the potential role of PAHs attached to PM2.5 and explore whether effects of these compounds may arise from disturbance of placental function or more directly by interfering with neurodevelopmental processes in the fetal brain. Possible molecular initiating events (MIEs) include interactions with cellular receptors such as the aryl hydrocarbon receptor (AhR), beta-adrenergic receptors (βAR) and transient receptor potential (TRP)-channels resulting in altered gene expression. MIE linked to the binding of PAHs to cytochrome P450 (CYP) enzymes and formation of reactive electrophilic metabolites are likely less important. The experimental animal and in vitro studies support the epidemiological findings and suggest steps involved in mechanistic pathways explaining the associations. An overall evaluation of the doses/concentrations used in experimental studies combined with the mechanistic understanding further supports the hypothesis that prenatal PAHs exposure may cause adverse outcomes (AOs) linked to human neurodevelopment. Several MIEs will likely occur simultaneously in various cells/tissues involving several key events (KEs) which relative importance will depend on dose, time, tissue, genetics, other environmental factors, and neurodevelopmental endpoint in study.

• Holme, Jørn Andreas; Låg, Marit; Skuland, Tonje Schwach; Parenicová, Martina; Ciganek, Miroslav & Penciková, Katerina [Vis alle 13 forfattere av denne artikkelen] (2023). Characterization of elements, PAHs, AhR-activity and pro-inflammatory responses of road tunnel-derived particulate matter in human hepatocyte-like and bronchial epithelial cells. Toxicology in Vitro. ISSN 0887-2333. 90, s. 1–13. doi: 10.1016/j.tiv.2023.105611. Fulltekst i vitenarkiv Vis sammendrag

  The aims were to characterize the content of elements and polycyclic aromatic hydrocarbons (PAHs) in size-separated particulate matter (PM) sampled in a road tunnel, estimate the contribution of PAHs to the toxic potential, and measure the pro-inflammatory potential of PM samples and extracts with increasing polarity. Several elements/metals previously associated with cytokine responses were found. Based on PAHs levels and published PAHs potency, the calculated mutagenic and carcinogenic activities of size-separated samples were somewhat lower for coarse than fine and ultrafine PM. The AhR-activity of the corresponding PM extracts measured in an AhR-luciferase reporter model (human hepatocytes) were more similar. The highest AhR-activity was found in the neutral (parent and alkylated PAHs) and polar (oxy-PAHs) fractions, while the semi-polar fractions (mono-nitrated-PAHs) had only weak activity. The neutral and polar aromatic fractions from coarse and fine PM were also found to induce higher pro-inflammatory responses and CYP1A1 expression in human bronchial epithelial cells (HBEC3-KT) than the semi-polar fractions. Fine PM induced higher pro-inflammatory responses than coarse PM. AhR-inhibition reduced cytokine responses induced by parent PM and extracts of both size fractions. Contributors to the toxic potentials include PAHs and oxy-PAHs, but substantial contributions from other organic compounds and/or metals are likely.

• Holme, Jørn Andreas; Vondráček, Jan; Machala, Miroslav; Lagadic-Gossmann, Dominique; Vogel, Christoph F.A & Ferrec, Eric Le [Vis alle 8 forfattere av denne artikkelen] (2023). Lung cancer associated with combustion particles and fine particulate matter (PM2.5) - The roles of polycyclic aromatic hydrocarbons (PAHs) and the aryl hydrocarbon receptor (AhR). Biochemical Pharmacology. ISSN 0006-2952. 216. doi: 10.1016/j.bcp.2023.115801. Fulltekst i vitenarkiv Vis sammendrag

  Air pollution is the leading cause of lung cancer after tobacco smoking, contributing to 20% of all lung cancer deaths. Increased risk associated with living near trafficked roads, occupational exposure to diesel exhaust, indoor coal combustion and cigarette smoking, suggest that combustion components in ambient fine particulate matter (PM2.5), such as polycyclic aromatic hydrocarbons (PAHs), may be central drivers of lung cancer. Activation of the aryl hydrocarbon receptor (AhR) induces expression of xenobiotic-metabolizing enzymes (XMEs) and increase PAH metabolism, formation of reactive metabolites, oxidative stress, DNA damage and mutagenesis. Lung cancer tissues from smokers and workers exposed to high combustion PM levels contain mutagenic signatures derived from PAHs. However, recent findings suggest that ambient air PM2.5 exposure primarily induces lung cancer development through tumor promotion of cells harboring naturally acquired oncogenic mutations, thus lacking typical PAH-induced mutations. On this background, we discuss the role of AhR and PAHs in lung cancer development caused by air pollution focusing on the tumor promoting properties including metabolism, immune system, cell proliferation and survival, tumor microenvironment, cell-to-cell communication, tumor growth and metastasis. We suggest that the dichotomy in lung cancer patterns observed between smoking and outdoor air PM2.5 represent the two ends of a dose–response continuum of combustion PM exposure, where tumor promotion in the peripheral lung appears to be the driving factor at the relatively low-dose exposures from ambient air PM2.5, whereas genotoxicity in the central airways becomes increasingly more important at the higher combustion PM levels encountered through smoking and occupational exposure.

• Refsnes, Magne; Skuland, Tonje; Jørgensen, Rikke; Grytting, Vegard Sæter; Snilsberg, Brynhild & Øvrevik, Johan [Vis alle 8 forfattere av denne artikkelen] (2023). Role of different mechanisms in pro-inflammatory responses triggered by traffic-derived particulate matter in human bronchiolar epithelial cells. Particle and Fibre Toxicology. 20(1). doi: 10.1186/s12989-023-00542-w. Fulltekst i vitenarkiv Vis sammendrag

  Background Traffic-derived particles are important contributors to the adverse health effects of ambient particulate matter (PM). In Nordic countries, mineral particles from road pavement and diesel exhaust particles (DEP) are important constituents of traffic-derived PM. In the present study we compared the pro-inflammatory responses of mineral particles and DEP to PM from two road tunnels, and examined the mechanisms involved. Methods The pro-inflammatory potential of 100 µg/mL coarse (PM10-2.5), fine (PM2.5-0.18) and ultrafine PM (PM0.18) sampled in two road tunnels paved with different stone materials was assessed in human bronchial epithelial cells (HBEC3-KT), and compared to DEP and particles derived from the respective stone materials. Release of pro-inflammatory cytokines (CXCL8, IL-1α, IL-1β) was measured by ELISA, while the expression of genes related to inflammation (COX2, CXCL8, IL-1α, IL-1β, TNF-α), redox responses (HO-1) and metabolism (CYP1A1, CYP1B1, PAI-2) was determined by qPCR. The roles of the aryl hydrocarbon receptor (AhR) and reactive oxygen species (ROS) were examined by treatment with the AhR-inhibitor CH223191 and the anti-oxidant N-acetyl cysteine (NAC). Results Road tunnel PM caused time-dependent increases in expression of CXCL8, COX2, IL-1α, IL-1β, TNF-α, COX2, PAI-2, CYP1A1, CYP1B1 and HO-1, with fine PM as more potent than coarse PM at early time-points. The stone particle samples and DEP induced lower cytokine release than all size-fractionated PM samples for one tunnel, and versus fine PM for the other tunnel. CH223191 partially reduced release and expression of IL-1α and CXCL8, and expression of COX2, for fine and coarse PM, depending on tunnel, response and time-point. Whereas expression of CYP1A1 was markedly reduced by CH223191, HO-1 expression was not affected. NAC reduced the release and expression of IL-1α and CXCL8, and COX2 expression, but augmented expression of CYP1A1 and HO-1. Conclusions The results indicate that the pro-inflammatory responses of road tunnel PM in HBEC3-KT cells are not attributed to the mineral particles or DEP alone. The pro-inflammatory responses seem to involve AhR-dependent mechanisms, suggesting a role for organic constituents. ROS-mediated mechanisms were also involved, probably through AhR-independent pathways. DEP may be a contributor to the AhR-dependent responses, although other sources may be of importance.

• Grytting, Vegard Sæter; Chand, Prem; Låg, Marit; Øvrevik, Johan & Refsnes, Magne Arnold (2022). The pro-inflammatory effects of combined exposure to diesel exhaust particles and mineral particles in human bronchial epithelial cells. Particle and Fibre Toxicology. 19(14). doi: 10.1186/s12989-022-00455-0. Fulltekst i vitenarkiv
• Moazami, Therese Nitter; Hilt, Bjørn; Sørås, Kirsti; Svendsen, Kristin V Hirsch; Dahlman, Hans Jørgen & Refsnes, Magne Arnold [Vis alle 9 forfattere av denne artikkelen] (2022). Short-term exposure to stone minerals used in asphalt affect lung function and promote pulmonary inflammation among healthy adults. Scandinavian Journal of Work, Environment and Health. ISSN 0355-3140. 48(5), s. 410–418. doi: 10.5271/sjweh.4023. Fulltekst i vitenarkiv Vis sammendrag

  Objective Stone minerals are a partially ignored environmental challenge but a significant contributor to urban air pollution. We examined if short-term exposure to two stone minerals – quartz diorite and rhomb porphyry – commonly used in asphalt pavement would affect lung function, promote pulmonary inflammation, and affect bronchial reactivity differently. Methods Our randomized crossover study included 24 healthy, non-smoking young adults exposed to the stone minerals quartz diorite, rhomb porphyry, and control dust (lactose). Exposure occurred in an exposure chamber, in three separate 4-hour exposure sessions. Fractional exhaled nitric oxide (FeNO) and lung function were monitored before exposure, then immediately following exposure, and 4 and 24 hours after exposure. In addition, methacholine was administered 4 hours following exposure, and exhaled breath condensate (EBC) was collected before exposure, then immediately and 4 hours after exposure. EBC was analyzed for pH, thiobarbituric acid reactive substances (TBARS), intercellular adhesion molecule 1 (ICAM-1), interleukin-6 (IL-6), IL-10, P-Selectin, surfactant protein D (SP-D), and tumor necrosis factor-α (TNF-α). Results Our results showed significantly elevated concentrations of FeNO after exposure to quartz diorite compared to rhomb porphyry, suggesting that quartz diorite is more likely to trigger pulmonary inflammation after short-term exposure. Moreover, short-term exposure to rhomb porphyry was associated with a modest but statistically significant decline in forced vital capacity (FVC) compared to quartz diorite. Conclusion These results emphasize that using stone material in asphalt road construction should be reconsidered as it may affect lung inflammation and lung function in exposed subjects.

• Oczkowski, Michał; Wilczak, Jacek; Dziendzikowska, Katarzyna; Øvrevik, Johan; Myhre, Oddvar & Lankoff, Anna [Vis alle 8 forfattere av denne artikkelen] (2022). Dietary Intervention with Blackcurrant Pomace Protects Rats from Testicular Oxidative Stress Induced by Exposition to Biodiesel Exhaust. Antioxidants. 11(8). doi: 10.3390/antiox11081562. Fulltekst i vitenarkiv Vis sammendrag

  The exposure to diesel exhaust emissions (DEE) contributes to negative health outcomes and premature mortality. At the same time, the health effects of the exposure to biodiesel exhaust emission are still in scientific debate. The aim of presented study was to investigate in an animal study the effects of exposure to DEE from two types of biodiesel fuels, 1st generation B7 biodiesel containing 7% of fatty acid methyl esters (FAME) or 2nd generation biodiesel (SHB20) containing 7% of FAME and 13% of hydrotreated vegetable oil (HVO), on the oxidative stress in testes and possible protective effects of dietary intervention with blackcurrant pomace (BC). Adult Fisher344/DuCrl rats were exposed by inhalation (6 h/day, 5 days/week for 4 weeks) to 2% of DEE from B7 or SHB20 fuel mixed with air. The animals from B7 (n = 14) and SHB20 (n = 14) groups subjected to filtered by a diesel particulate filter (DPF) or unfiltered DEE were maintained on standard feed. The rats from B7+BC (n = 12) or SHB20+BC (n = 12), exposed to DEE in the same way, were fed with feed supplemented containing 2% (m/m) of BC. The exposure to exhaust emissions from 1st and 2nd generation biodiesel resulted in induction of oxidative stress in the testes. Higher concentration of the oxidative stress markers thiobarbituric acid-reactive substances (TBARS), lipid hydroperoxides (LOOHs), 25-dihydroxycholesterols (25(OH)2Ch), and 7-ketocholesterol (7-KCh) level), as well as decreased level of antioxidant defense systems such as reduced glutathione (GSH), GSH/GSSG ratio, and increased level of oxidized glutathione (GSSG)) were found. Dietary intervention reduced the concentration of TBARS, 7-KCh, LOOHs, and the GSSG level, and elevated the GSH level in testes. In conclusion, DEE-induced oxidative stress in the testes was related to the biodiesel feedstock and the application of DPF. The SHB20 DEE without DPF technology exerted the most pronounced toxic effects. Dietary intervention with BC in rats exposed to DEE reduced oxidative stress in testes and improved antioxidative defense parameters, however the redox balance in the testes was not completely restored.

• Skuland, Tonje Schwach; Grytting, Vegard Sæter; Låg, Marit; Jørgensen, Rikke Bramming; Snilsberg, Brynhild & Leseman, Daan L.A.C. [Vis alle 12 forfattere av denne artikkelen] (2022). Road tunnel-derived coarse, fine and ultrafine particulate matter: physical and chemical characterization and pro-inflammatory responses in human bronchial epithelial cells. Particle and Fibre Toxicology. 19(45). doi: 10.1186/s12989-022-00488-5. Fulltekst i vitenarkiv Vis sammendrag

  Background Traffic particulate matter (PM) comprises a mixture of particles from fuel combustion and wear of road pavement, tires and brakes. In countries with low winter temperatures the relative contribution of mineral-rich PM from road abrasion may be especially high due to use of studded tires during winter season. The aim of the present study was to sample and characterize size-fractioned PM from two road tunnels paved with different stone materials in the asphalt, and to compare the pro-inflammatory potential of these fractions in human bronchial epithelial cells (HBEC3-KT) in relation to physicochemical characteristics. Methods The road tunnel PM was collected with a vacuum pump and a high-volume cascade impactor sampler. PM was sampled during winter, both during humid and dry road surface conditions, and before and after cleaning the tunnels. Samples were analysed for hydrodynamic size distribution, content of elemental carbon (EC), organic carbon (OC) and endotoxin, and the capacity for acellular generation of reactive oxygen species. Cytotoxicity and pro-inflammatory responses were assessed in HBEC3-KT cells after exposure to coarse (2.5–10 μm), fine (0.18–2.5 μm) and ultrafine PM (≤ 0.18 μm), as well as particles from the respective stone materials used in the pavement. Results The pro-inflammatory potency of the PM samples varied between road tunnels and size fractions, but showed more marked responses than for the stone materials used in asphalt of the respective tunnels. In particular, fine samples showed significant increases as low as 25 µg/mL (2.6 µg/cm2) and were more potent than coarse samples, while ultrafine samples showed more variable responses between tunnels, sampling conditions and endpoints. The most marked responses were observed for fine PM sampled during humid road surface conditions. Linear correlation analysis showed that particle-induced cytokine responses were correlated to OC levels, while no correlations were observed for other PM characteristics. Conclusions The pro-inflammatory potential of fine road tunnel PM sampled during winter season was high compared to coarse PM. The differences between the PM-induced cytokine responses were not related to stone materials in the asphalt. However, the ratio of OC to total PM mass was associated with the pro-inflammatory potential.

• Holme, Jørn Andreas; Valen, Håkon; Brinchmann, Bendik Christian; Vist, Gunn Elisabeth; Grimsrud, Tom Kristian & Becher, Rune [Vis alle 9 forfattere av denne artikkelen] (2022). Polycyclic aromatic hydrocarbons (PAHs) may explain the paradoxical effects of cigarette use on preeclampsia (PE). Toxicology. ISSN 0300-483X. 473. doi: 10.1016/j.tox.2022.153206. Fulltekst i vitenarkiv Vis sammendrag

  Tobacco smoking and use of snus (smokeless tobacco) are associated with adverse effects on pregnancy and neonatal outcomes. Nicotine is considered a key toxicant involved in effects caused by both smoking and snus, while pyrolysis products including polycyclic aromatic hydrocarbons (PAHs) in cigarette smoke represents the constituents most unequally divided between these two groups of tobacco products. The aim of this review was: i) to compare the impact, in terms of relative effect estimates, of cigarette smoking and use of Swedish snus on pregnancy outcomes using similar non-tobacco user controls, and ii) to examine whether exposure to PAHs from smoking could explain possible differences in impact on pregnancy outcomes. We systematically searched MEDLINE, Embase, PsycInfo, Web of Science and the Cochrane Database of Systematic Reviews up to October 2021 and identified studies reporting risks for adverse pregnancy and neonatal outcomes associated with snus use and with smoking relative to pregnant women with no use of tobacco. Both snus use and smoking were associated with increased risk of stillbirth, preterm birth, and oral cleft malformation, with comparable point estimates. These effects were likely due to comparable nicotine exposure. We also found striking differences. While both smoking and snus increased the risk of having small for gestational age (SGA) infants, risk from maternal smoking was markedly higher as was the reduction in birthweight. In contrast, the risk of preeclampsia (PE) was markedly lower in smokers than in controls, while snus use was associated with a slightly increased risk. We suggest that PAHs acting via AhR may explain the stronger effects of tobacco smoking on SGA and also to the apparent protective effect of cigarette smoking on PE. Possible mechanisms involved include: i) disrupted endocrine control of fetal development as well as placental development and function, and ii) stress adaption and immune suppression in placenta and mother.

• Grytting, Vegard Sæter; Refsnes, Magne Arnold; Låg, Marit; Erichsen, Eyolf; Røhr, Torkil Sørlie & Snilsberg, Brynhild [Vis alle 8 forfattere av denne artikkelen] (2022). The importance of mineralogical composition for the cytotoxic and pro-inflammatory effects of mineral dust. Particle and Fibre Toxicology. 19(1). doi: 10.1186/s12989-022-00486-7. Fulltekst i vitenarkiv Vis sammendrag

  Background Respirable mineral particles represent a potential health hazard in occupational settings and ambient air. Previous studies show that mineral particles may induce cytotoxicity and inflammatory reactions in vitro and in vivo and that the potency varies between samples of different composition. However, the reason for these differences is largely unknown and the impact of mineralogical composition on the biological effects of mineral dust remains to be determined. Methods We have assessed the cytotoxic and pro-inflammatory effects of ten mineral particle samples of different composition in human bronchial epithelial cells (HBEC3-KT) and THP-1-derived macrophages, as well as their membranolytic properties in erythrocytes. Moreover, the results were compiled with the results of recently published experiments on the effects of stone particle exposure and analysed using linear regression models to elucidate which mineral components contribute most to the toxicity of mineral dust. Results While all mineral particle samples were more cytotoxic to HBEC3-KT cells than THP-1 macrophages, biotite and quartz were among the most cytotoxic in both cell models. In HBEC3-KT cells, biotite and quartz also appeared to be the most potent inducers of pro-inflammatory cytokines, while the quartz, Ca-feldspar, Na-feldspar and biotite samples were the most potent in THP-1 macrophages. All particle samples except quartz induced low levels of membranolysis. The regression analyses revealed associations between particle bioactivity and the content of quartz, muscovite, plagioclase, biotite, anorthite, albite, microcline, calcite, chlorite, orthopyroxene, actinolite and epidote, depending on the cell model and endpoint. However, muscovite was the only mineral consistently associated with increased cytotoxicity and cytokine release in both cell models. Conclusions The present study provides further evidence that mineral particles may induce cytotoxicity and inflammation in cells of the human airways and that particle samples of different mineralogical composition differ in potency. The results show that quartz, while being among the most potent samples, does not fully predict the toxicity of mineral dust, highlighting the importance of other particle constituents. Moreover, the results indicate that the phyllosilicates muscovite and biotite may be more potent than other minerals assessed in the study, suggesting that this group of sheet-like minerals may warrant further attention.

• Brinchmann, Bendik Christian; Holme, Jørn Andreas; Frerker, Nadine; Rambøl, Mia Marie-Elisabeth; Karlsen, Tommy Aleksander & Brinchmann, Jan E. [Vis alle 10 forfattere av denne artikkelen] (2022). Effects of organic chemicals from diesel exhaust particles on adipocytes differentiated from human mesenchymal stem cells. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 132(1), s. 83–97. doi: 10.1111/bcpt.13805. Fulltekst i vitenarkiv Vis sammendrag

  Exposure to fine particulate matter (PM2.5) from incomplete fossil fuel combustion (coal, oil, gas and diesel) has been linked to increased morbidity and mortality due to metabolic diseases. PM2.5 exaggerate adipose inflammation and insulin resistance in mice with diet-induced obesity. Here, we elucidate the hypothesis that such systemic effects may be triggered by adhered particle components affecting adipose tissue directly. Studying adipocytes differentiated from primary human mesenchymal stem cells, we found that lipophilic organic chemicals (OC) from diesel exhaust particles induced inflammation-associated genes and increased secretion of the chemokine CXLC8/interleukin-8 as well as matrix metalloprotease 1. The oxidative stress response gene haem oxygenase-1 and tumour necrosis factor alpha were seemingly not affected, while aryl hydrocarbon receptor-regulated genes, cytochrome P450 1A1 (CYP1A1) and CYP1B1 and plasminogen activator inhibitor-2, were clearly up-regulated. Finally, expression of β-adrenergic receptor, known to regulate adipocyte homoeostasis, was down-regulated by exposure to these lipophilic OC. Our results indicate that low concentrations of OC from combustion particles have the potential to modify expression of genes in adipocytes that may be linked to metabolic disease. Further studies on mechanisms linking PM exposure and metabolic diseases are warranted.

• Grytting, Vegard Sæter; Refsnes, Magne Arnold; Øvrevik, Johan; Halle, Marit Sigrid; Schönenberger, Jasmin & Lelij, Roelant van der [Vis alle 10 forfattere av denne artikkelen] (2021). Respirable stone particles differ in their ability to induce cytotoxicity and pro-inflammatory responses in cell models of the human airways. Particle and Fibre Toxicology. 18(1). doi: 10.1186/s12989-021-00409-y. Fulltekst i vitenarkiv Vis sammendrag

  Background Respirable stone- and mineral particles may be a major constituent in occupational and ambient air pollution and represent a possible health hazard. However, with exception of quartz and asbestos, little is known about the toxic properties of mineral particles. In the present study, the pro-inflammatory and cytotoxic responses to six stone particle samples of different composition and with diameter below 10 μm were assessed in human bronchial epithelial cells (HBEC3-KT), THP-1 macrophages and a HBEC3-KT/THP-1 co-culture. Moreover, particle-induced lysis of human erythrocytes was assessed to determine the ability of the particles to lyse biological membranes. Finally, the role of the NLRP3 inflammasome was assessed using a NLRP3-specific inhibitor and detection of ASC oligomers and cleaved caspase-1 and IL-1β. A reference sample of pure α-quartz was included for comparison. Results Several stone particle samples induced a concentration-dependent increase in cytotoxicity and secretion of the pro-inflammatory cytokines CXCL8, IL-1α, IL-1β and TNFα. In HBEC3-KT, quartzite and anorthosite were the most cytotoxic stone particle samples and induced the highest levels of cytokines. Quartzite and anorthosite were also the most cytotoxic samples in THP-1 macrophages, while anorthosite and hornfels induced the highest cytokine responses. In comparison, few significant differences between particle samples were detected in the co-culture. Adjusting responses for differences in surface area concentrations did not fully account for the differences between particle samples. Moreover, the stone particles had low hemolytic potential, indicating that the effects were not driven by membrane lysis. Pre-incubation with a NLRP3-specific inhibitor reduced stone particle-induced cytokine responses in THP-1 macrophages, but not in HBEC3-KT cells, suggesting that the effects are mediated through different mechanisms in epithelial cells and macrophages. Particle exposure also induced an increase in ASC oligomers and cleaved caspase-1 and IL-1β in THP-1 macrophages, confirming the involvement of the NLRP3 inflammasome. Conclusions The present study indicates that stone particles induce cytotoxicity and pro-inflammatory responses in human bronchial epithelial cells and macrophages, acting through NLRP3-independent and -dependent mechanisms, respectively. Moreover, some particle samples induced cytotoxicity and cytokine release to a similar or greater extent than α-quartz. Thus, these minerals warrant further attention in future research.

• Refsnes, Magne Arnold; Skuland, Tonje Schwach; Øvrevik, Johan & Låg, Marit (2021). Role of scavenger receptors in silica nanoparticle-induced cytokine responses in bronchial epithelial cells. Toxicology Letters. ISSN 0378-4274. 353, s. 100–106. doi: 10.1016/j.toxlet.2021.10.004. Fulltekst i vitenarkiv
• Marchetti, Sara; Mollerup, Steen Kristen; Gutzkow, Kristine Bjerve; Rizzi, Cristiana; Skuland, Tonje Schwach & Refsnes, Magne Arnold [Vis alle 10 forfattere av denne artikkelen] (2021). Biological effects of combustion-derived particles from different biomass sources on human bronchial epithelial cells. Toxicology in Vitro. ISSN 0887-2333. 75. doi: 10.1016/j.tiv.2021.105190. Fulltekst i vitenarkiv Vis sammendrag

  Combustion-derived particles (CDPs), in particular from traffic, are regarded as a central contributor for adverse health effects linked to air pollution. Recently, also biomass burning has been recognized as an important source for CDPs. Here, the effects of CDPs (PM10) originating from burning of pellet, charcoal and wood on key processes associated to lung carcinogenesis were explored. Human bronchial epithelial cells (HBEC3-KT) were exposed to 2.5 μg/cm2 of CDPs for 24 h and biological effects were examined in terms of cytotoxicity, inflammation, epithelial to mesenchymal transition (EMT)-related effects, DNA damage and genotoxicity. Reduced cell migration, inflammation and modulation of various PM-associated genes were observed mainly after exposure to wood and pellet. In contrast, only particles from pellet burning induced alteration in cell proliferation and DNA damage, which resulted in cell cycle alterations. Charcoal instead, appeared in general less effective in inducing pro-carcinogenic effects. These results illustrate differences in the toxicological profile due to the CDPs source. The different chemical compounds adsorbed on CDPs seemed to be central for particle properties, leading to an activation of various cellular signaling pathways involved in early steps of cancer progression.

• Moazami, Therese Nitter; Hilt, Bjørn; Svendsen, Kristin V Hirsch; Buhagen, Morten; Dahlman, Hans Jørgen & Øvrevik, Johan [Vis alle 8 forfattere av denne artikkelen] (2021). Inflammatory effects of exposure to different stone types used in Norwegian asphalt. SINTEF proceedings. ISSN 2387-4287. s. 538–545. Fulltekst i vitenarkiv
• Berntsen, Hanne Friis; Bodin, Johanna Eva; Øvrevik, Johan; Berntsen, Christopher Friis; Østby, Gunn Charlotte & Brinchmann, Bendik Christian [Vis alle 8 forfattere av denne artikkelen] (2021). A human relevant mixture of persistent organic pollutants induces reactive oxygen species formation in isolated human leucocytes: Involvement of the β2-adrenergic receptor. Environment International. ISSN 0160-4120. 158. doi: 10.1016/j.envint.2021.106900. Fulltekst i vitenarkiv Vis sammendrag

  Exposure to chlorinated (Cl), brominated (Br) and perfluoroalkyl acid (PFAA) persistent organic pollutants (POPs) is associated with immunotoxicity and other adverse effects in humans and animals. Previous studies on POPs have mainly focused on single chemicals, while studies on complex mixtures are limited. Using DCF and luminol assays we examined effects on ROS generation in isolated human neutrophils, monocytes and lymphocytes, after in vitro exposure to a total mixture and sub-mixtures of 29 persistent compounds (Cl, Br, and PFAA). The mixtures were based on compounds prominent in blood, breast milk, and/or food. All mixture combinations induced ROS production in one or several of the cell models, and in some cases even at concentrations corresponding to human blood levels (compound range 1 pM – 16 nM). Whilst some interactions were detected (assessed using a mixed linear model), halogenated subgroups mainly acted additively. Mechanistic studies in neutrophils at 500× human levels (0.5 nM – 8 µM) indicated similar mechanisms of action for the Cl, PFAA, the combined PFAA + Cl and total (PFAA + Br + Cl) mixtures, and ROS responses appeared to involve β2-adrenergic receptor (β2AR) and Ca2+ signalling, as well as activation of NADPH oxidases. In line with this, the total mixture also increased cyclic AMP at levels comparable with the non-selective βAR agonist, isoproterenol. Although the detailed mechanisms involved in these responses remain to be elucidated, our data show that POP mixtures at concentrations found in human blood, may trigger stress responses in circulating immune cells. Mixtures of POPs, further seemed to interfere with adrenergic pathways, indicating a novel role of βARs in POP-induced effects.

• Skuland, Tonje Schwach; Låg, Marit; Gutleb, Arno; Brinchmann, Bendik Christian; Serchi, Tommaso & Øvrevik, Johan [Vis alle 8 forfattere av denne artikkelen] (2020). Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model. Particle and Fibre Toxicology. 17(1), s. 1–18. doi: 10.1186/s12989-020-00345-3. Fulltekst i vitenarkiv Vis sammendrag

  Background Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression. Results Exposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments. Conclusions Si10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages.

• Holme, Jørn Andreas; Øya, Elisabeth; Afanou, Komlavi Anani; Øvrevik, Johan & Wijnand, Eduard (2020). Characterization and pro‐inflammatory potential of indoor mold particles. Indoor Air. ISSN 0905-6947. 30(4), s. 662–681. doi: 10.1111/ina.12656. Fulltekst i vitenarkiv Vis sammendrag

  A number of epidemiological studies find an association between indoor air dampness and respiratory health effects. This is often suggested to be linked to enhanced mold growth. However, the role of mold are obviously difficult to disentangle from other dampness related exposure including microbes as well as non‐biological particles and chemical pollutants. The association may partly be due to visible mycelial growth and a characteristic musty smell of mold. Thus, the potential role of mold exposure should be further explored by evaluating information from experimental studies elucidating possible mechanistic links. Such studies show that exposure to spores and hyphal fragments may act as allergens and pro‐inflammatory mediators, and that they may damage airways by the production of toxins, enzymes and volatile organic compounds. In the present review, we hypothesizes that continuous exposure to mold particles may result in chronic low‐grade pro‐inflammatory responses contributing to respiratory diseases. We summarize some of the main methods for detection and characterization of fungal aerosols and highlight in vitro research elucidating how molds may induce toxicity and pro‐inflammatory reactions in human cell models relevant for airway exposure. Data suggest that the fraction of fungal hyphal fragments in indoor air is much higher than that of airborne spores, and the hyphal fragments often have a higher pro‐inflammatory potential. Thus, hyphal fragments of prevalent mold species with strong pro‐inflammatory potential may be particularly relevant candidates for respiratory diseases associated with damp/mold‐contaminated indoor air. Future studies linking of indoor air dampness with health effects should assess the toxicity and pro‐inflammatory potential of indoor air particulate matter, and combined this information with a better characterization of biological components including hyphal fragments from both pathogenic and non‐pathogenic mold species. Such studies may increase our understanding of the potential role of mold exposure.

• Villanger, Gro Dehli; Øvrevik, Johan; Aase, Heidi & Myhre, Oddvar (2020). Early-Life Environmental Toxic Influences on Neural Development. I Xia, Yankai (Red.), Early-life Environmental Exposure and Disease. Springer. ISSN 9789811537967. s. 141–159. doi: 10.1007/978-981-15-3797-4_8. Fulltekst i vitenarkiv
• Låg, Marit; Øvrevik, Johan; Refsnes, Magne Arnold & Holme, Jørn Andreas (2020). Potential role of polycyclic aromatic hydrocarbons in air pollution-induced non-malignant respiratory diseases. Respiratory Research. ISSN 1465-9921. 21. doi: 10.1186/s12931-020-01563-1. Fulltekst i vitenarkiv Vis sammendrag

  Epidemiological studies have found strong associations between air pollution and respiratory effects including development and/or exacerbation of asthma and chronic obstructive pulmonary disease (COPD) as well as increased occurrence of respiratory infections and lung cancer. It has become increasingly clear that also polycyclic aromatic hydrocarbons (PAHs) may affect processes linked to non-malignant diseases in the airways. The aim of the present paper was to review epidemiological studies on associations between gas phase and particle-bound PAHs in ambient air and non-malignant respiratory diseases or closely related physiological processes, to assess whether PAH-exposure may explain some of the effects associated with air pollution. Based on experimental in vivo and in vitro studies, we also explore possible mechanisms for how different PAHs may contribute to such events. Epidemiological studies show strongest evidence for an association between PAHs and asthma development and respiratory function in children. This is supported by studies on prenatal and postnatal exposure. Exposure to PAHs in adults seems to be linked to respiratory functions, exacerbation of asthma and increased morbidity/mortality of obstructive lung diseases. However, available studies are few and weak. Notably, the PAHs measured in plasma/urine also represent other exposure routes than inhalation. Furthermore, the role of PAHs measured in air is difficult to disentangle from that of other air pollution components originating from combustion processes. Experimental studies show that PAHs may trigger various processes linked to non-malignant respiratory diseases. Physiological- and pathological responses include redox imbalance, oxidative stress, inflammation both from the innate and adaptive immune systems, smooth muscle constriction, epithelial- and endothelial dysfunction and dysregulated lung development. Such biological responses may at the molecular level be initiated by PAH-binding to the aryl hydrocarbon receptor (AhR), but possibly also through interactions with beta-adrenergic receptors. In addition, reactive PAH metabolites or reactive oxygen species (ROS) may interfere directly with ion transporters and enzymes involved in signal transduction. Overall, the reviewed literature shows that respiratory effects of PAH-exposure in ambient air may extend beyond lung cancer. The relative importance of the specific PAHs ability to induce disease may differ between the biological endpoint in question.

• Holme, Jørn Andreas; Brinchmann, Bendik Christian; Ferrec, Eric Le; Lagadic-Gossmann, Dominique & Øvrevik, Johan (2019). Combustion particle-induced changes in calcium homeostasis: A contributing factor to vascular disease? Cardiovascular Toxicology. ISSN 1530-7905. 19(3), s. 198–209. doi: 10.1007/s12012-019-09518-9. Fulltekst i vitenarkiv
• Øvrevik, Johan (2019). Oxidative potential versus biological effects: A review on the relevance of cell-free/abiotic assays as predictors of toxicity from airborne particulate matter. International Journal of Molecular Sciences. ISSN 1661-6596. 20(19), s. 1–21. doi: 10.3390/ijms20194772. Fulltekst i vitenarkiv Vis sammendrag

  Background and Objectives: The oxidative potential (OP) of particulate matter (PM) in cell-free/abiotic systems have been suggested as a possible measure of their biological reactivity and a relevant exposure metric for ambient air PM in epidemiological studies. The present review examined whether the OP of particles correlate with their biological effects, to determine the relevance of these cell-free assays as predictors of particle toxicity. Methods: PubMed, Google Scholar and Web of Science databases were searched to identify relevant studies published up to May 2019. The main inclusion criteria used for the selection of studies were that they should contain (1) multiple PM types or samples, (2) assessment of oxidative potential in cell-free systems and (3) assessment of biological effects in cells, animals or humans. Results: In total, 50 independent studies were identified assessing both OP and biological effects of ambient air PM or combustion particles such as diesel exhaust and wood smoke particles: 32 in vitro or in vivo studies exploring effects in cells or animals, and 18 clinical or epidemiological studies exploring effects in humans. Of these, 29 studies assessed the association between OP and biological effects by statistical analysis: 10 studies reported that at least one OP measure was statistically significantly associated with all endpoints examined, 12 studies reported that at least one OP measure was significantly associated with at least one effect outcome, while seven studies reported no significant correlation/association between any OP measures and any biological effects. The overall assessment revealed considerable variability in reported association between individual OP assays and specific outcomes, but evidence of positive association between intracellular ROS, oxidative damage and antioxidant response in vitro, and between OP assessed by the dithiothreitol (DDT) assay and asthma/wheeze in humans. There was little support for consistent association between OP and any other outcome assessed, either due to repeated lack of statistical association, variability in reported findings or limited numbers of available studies. Conclusions: Current assays for OP in cell-free/abiotic systems appear to have limited value in predicting PM toxicity. Clarifying the underlying causes may be important for further advancement in the field.

• Øya, Elisabeth; Zegeye, Fikirte Debebe; Bølling, Anette Kocbach; Øvstebø, Reidun; Afanou, Komlavi Anani & Øvrevik, Johan [Vis alle 8 forfattere av denne artikkelen] (2019). Hyphae fragments from A. fumigatus sensitize lung cells to silica particles (Min-U-Sil): Increased release of IL-1? Toxicology in Vitro. ISSN 0887-2333. 55, s. 1–10. doi: 10.1016/j.tiv.2018.11.002. Fulltekst i vitenarkiv Vis sammendrag

  Exposure to particulate matter (PM), such as mineral particles and biological particles/components may be linked to aggravation of respiratory diseases, including asthma. Here we report that exposure to Aspergillus fumigatus hyphae fragments (AFH) and lipopolysaccharide (LPS) induced both mRNA synthesis and release of pro-inflammatory interleukin-1 beta (IL-1β) in both human THP-1 monocytes (THP-1 Mo) and phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 monocytes (THP-1 macrophages; THP-1 Ma); while Min-U-Sil alone enhanced the release of IL-1β only in THP-1 Ma. Co-exposure to LPS or AFH with Min-U-Sil caused a synergistic release of IL-1β when compared to single exposures. In contrast, Min-U-Sil did not markedly change LPS- and AFH-induced release of tumor necrosis factor alpha (TNF-α). The combined exposures did not increase the LPS- and AFH-induced expression of IL-1β mRNA. Notably, the AFH- and LPS-induced IL-1β responses with and without co-exposure to Min-U-Sil in THP-1 Mo were found to be caspase-dependent as shown by inhibition with zYVAD-fmk. Furthermore, co-exposure with AFH and Min-U-Sil resulted in similar synergistic releases of IL-1β in primary human airway macrophages (AM; sputum), peripheral blood monocyte-derived macrophages (MDM) and in the human bronchial epithelial cell line (BEAS-2B). In conclusion, AFH induce both the synthesis and release of IL-1β. However, Min-U-Sil further enhanced the cleavage of the induced pro-IL-1β.

• Magnusson, Pål Amdal; Dziendzikowska, Katarzyna; Oczkowski, Michał; Øvrevik, Johan; Eide, Dag Markus & Brunborg, Gunnar [Vis alle 19 forfattere av denne artikkelen] (2019). Lung effects of 7- and 28-day inhalation exposure of rats to emissions from 1st and 2nd generation biodiesel fuels with and without particle filter - The FuelHealth project. Environmental Toxicology and Pharmacology. ISSN 1382-6689. 67, s. 8–20. doi: 10.1016/j.etap.2019.01.005. Fulltekst i vitenarkiv
• Brinchmann, Bendik Christian; Ferrec, Eric Le; Podechard, Normand; Lagadic-Gossmann, Dominique; Holme, Jørn Andreas & Øvrevik, Johan (2019). Organic chemicals from diesel exhaust particles affects intracellular calcium, inflammation and β-adrenoceptors in endothelial cells. Toxicology Letters. ISSN 0378-4274. 302, s. 18–27. doi: 10.1016/j.toxlet.2018.11.009. Fulltekst i vitenarkiv Vis sammendrag

  Exposure to diesel exhaust particles (DEP) may contribute to endothelial dysfunction and cardiovascular disease. DEP, extractable organic material from DEP (DEP-EOM) and certain PAHs seem to trigger [Ca2+]i increase as well as inflammation via GPCRs like βARs and PAR-2. In the present study we explored the involvement of βARs and PAR-2 in effects of DEP-EOM on [Ca2+]i and expression of inflammation-associated genes in the endothelial cell-line HMEC-1. We exposed the human microvascular endothelial cell line HMEC-1 to DEP-EOM fractionated by sequential extraction with solvents of increasing polarity: n-hexane (n-Hex-EOM), dichloromethane (DCM-EOM), methanol (Methanol-EOM) and water (Water-EOM). While Methanol-EOM and Water-EOM had no marked effects, n-Hex-EOM and DCM-EOM enhanced [Ca2+]i (2–3 times baseline) and expression of inflammation-associated genes (IL-1α, IL-1β, COX-2 and CXCL8; 2–15 times baseline) in HMEC-1. The expression of βARs (60–80% of baseline) and βAR-inhibitor carazolol suppressed the increase in [Ca2+]i induced by both n-Hex- and DCM-EOM. Carazolol as well as the Ca2+-channel inhibitor SKF-96365 reduced the DCM-EOM-induced pro-inflammatory gene-expression. Overexpression of βARs increased DCM-EOM-induced [Ca2+]i responses in HEK293 cells, while βAR-overexpression suppressed [Ca2+]i responses from n-Hex-EOM. Furthermore, the PAR-2-inhibitor ENMD-1068 attenuated [Ca2+]i responses to DCM-EOM, but not n-Hex-EOM in HMEC-1. The results suggest that βAR and PAR-2 are partially involved in effects of complex mixtures of chemicals extracted from DEP on calcium signalling and inflammation-associated genes in the HMEC-1 endothelial cell-line.

• Refsnes, Magne Arnold; Skuland, Tonje Schwach; Lilleaas, Edel Marie; Øvrevik, Johan & Låg, Marit (2019). Concentration-dependent cytokine responses of silica nanoparticles and role of ROS in human lung epithelial cells. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. s. 1–11. doi: 10.1111/bcpt.13221. Fulltekst i vitenarkiv
• Øya, Elisabeth; Becher, Rune; Ekeren, Leni Johanne; Afanou, Komlavi Anani; Øvrevik, Johan & Holme, Jørn Andreas (2019). Pro-Inflammatory Responses in Human Bronchial Epithelial Cells Induced by Spores and Hyphal Fragments of Common Damp Indoor Molds. International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 16(6), s. 1–16. doi: 10.3390/ijerph16061085. Fulltekst i vitenarkiv Vis sammendrag

  Damp indoor environments contaminated with different mold species may contribute to the development and exacerbation of respiratory illnesses. Human bronchial epithelial BEAS-2B cells were exposed to X-ray treated spores and hyphal fragments from pure cultures of Aspergillus fumigatus, Penicillum chrysogenum, Aspergillus versicolor and Stachybotrys chartarum. Hyphal fragments of A. fumigatus and P. chrysogenum induced expression and release of the pro-inflammatory cytokine interleukin (IL)-6 and the chemokine IL-8, while none of the other hyphal preparations had effects. Hyphal fragments from A. fumigatus and P. chrysogenum also increased the expression of IL-1α, IL-1β and tumor necrosis factor (TNF)-α, but these cytokines were not released. X-ray treated spores had little or no inflammatory potential. Attenuating Toll-like receptor (TLR)-2 by blocking antibodies strongly reduced the A. fumigatus and P. chrysogenum hyphae-induced IL-6 and IL-8 release, whereas TLR4 antagonist treatment was without effects. Untreated A. fumigatus spores formed hyphae and triggered expression of pro-inflammatory genes with similarities to the effects of hyphal fragments. In conclusion, while X-ray treated spores induced no pro-inflammatory responses, hyphal fragments of A. fumigatus and P. chrysogenum enhanced a TLR2-dependent expression and release of IL-6 and IL-8.

• Holme, Jørn Andreas; Brinchmann, Bendik Christian; Refsnes, Magne Arnold; Låg, Marit & Øvrevik, Johan (2019). Potential role of polycyclic aromatic hydrocarbons as mediators of cardiovascular effects from combustion particles. Environmental health. 18(74), s. 1–18. doi: 10.1186/s12940-019-0514-2. Fulltekst i vitenarkiv Vis sammendrag

  Air pollution is the most important environmental risk factor for disease and premature death, and exposure to combustion particles from vehicles is a major contributor. Human epidemiological studies combined with experimental studies strongly suggest that exposure to combustion particles may enhance the risk of cardiovascular disease (CVD), including atherosclerosis, hypertension, thrombosis and myocardial infarction. In this review we hypothesize that adhered organic chemicals like polycyclic aromatic hydrocarbons (PAHs), contribute to development or exacerbation of CVD from combustion particles exposure. We summarize present knowledge from existing human epidemiological and clinical studies as well as experimental studies in animals and relevant in vitro studies. The available evidence suggests that organic compounds attached to these particles are significant triggers of CVD. Furthermore, their effects seem to be mediated at least in part by the aryl hydrocarbon receptor (AhR). The mechanisms include AhR-induced changes in gene expression as well as formation of reactive oxygen species (ROS) and/or reactive electrophilic metabolites. This is in accordance with a role of PAHs, as they seem to be the major chemical group on combustion particles, which bind AhR and/or is metabolically activated by CYP-enzymes. In some experimental models however, it seems as PAHs may induce an inflammatory atherosclerotic plaque phenotype irrespective of DNA- and/or AhR-ligand binding properties. Thus, various components and several signalling mechanisms/pathways are likely involved in CVD induced by combustion particles. We still need to expand our knowledge about the role of PAHs in CVD and in particular the relative importance of the different PAH species. This warrants further studies as enhanced knowledge on this issue may amend risk assessment of CVD caused by combustion particles and selection of efficient measures to reduce the health effects of particular matters (PM).

• Brinchmann, Bendik Christian; Ferrec, Eric Le; Podechard, Normand; Lagadic-Gossmann, Dominique; Shoji, Kenji F. & Penna, Aubin [Vis alle 10 forfattere av denne artikkelen] (2018). Lipophilic chemicals from diesel exhaust particles trigger calcium response in human endothelial cells via aryl hydrocarbon receptor non-genomic signalling. International Journal of Molecular Sciences. ISSN 1661-6596. 19(5). doi: 10.3390/ijms19051429. Fulltekst i vitenarkiv Vis sammendrag

  Exposure to diesel exhaust particles (DEPs) affects endothelial function and may contribute to the development of atherosclerosis and vasomotor dysfunction. As intracellular calcium concentration [Ca2+]i is considered important in myoendothelial signalling, we explored the effects of extractable organic matter from DEPs (DEP-EOM) on [Ca2+]i and membrane microstructure in endothelial cells. DEP-EOM of increasing polarity was obtained by pressurized sequential extraction of DEPs with n-hexane (n-Hex-EOM), dichloromethane (DCM-EOM), methanol, and water. Chemical analysis revealed that the majority of organic matter was extracted by the n-Hex- and DCM-EOM, with polycyclic aromatic hydrocarbons primarily occurring in n-Hex-EOM. The concentration of calcium was measured in human microvascular endothelial cells (HMEC-1) using micro-spectrofluorometry. The lipophilic n-Hex-EOM and DCM-EOM, but not the more polar methanol- and water-soluble extracts, induced rapid [Ca2+]i increases in HMEC-1. n-Hex-EOM triggered [Ca2+]i increase from intracellular stores, followed by extracellular calcium influx consistent with store operated calcium entry (SOCE). By contrast, the less lipophilic DCM-EOM triggered [Ca2+]i increase via extracellular influx alone, resembling receptor operated calcium entry (ROCE). Both extracts increased [Ca2+]i via aryl hydrocarbon receptor (AhR) non-genomic signalling, verified by pharmacological inhibition and RNA-interference. Moreover, DCM-EOM appeared to induce an AhR-dependent reduction in the global plasma membrane order, as visualized by confocal fluorescence microscopy. DCM-EOM-triggered [Ca2+]i increase and membrane alterations were attenuated by the membrane stabilizing lipid cholesterol. In conclusion, lipophilic constituents of DEPs extracted by n-hexane and DCM seem to induce rapid AhR-dependent [Ca2+]i increase in HMEC-1 endothelial cells, possibly involving both ROCE and SOCE-mediated mechanisms. The semi-lipophilic fraction extracted by DCM also caused an AhR-dependent reduction in global membrane order, which appeared to be connected to the [Ca2+]i increase.

• Brinchmann, Bendik Christian; Ferrec, Eric Le; Bisson, William H; Podechard, Normand; Huitfeldt, Henrik & Gallais, Isabelle [Vis alle 10 forfattere av denne artikkelen] (2018). Evidence of Selective Activation of Aryl Hydrocarbon Receptor Nongenomic Calcium Signaling by Pyrene. Biochemical Pharmacology. ISSN 0006-2952. 158, s. 1–12. doi: 10.1016/j.bcp.2018.09.023. Fulltekst i vitenarkiv Vis sammendrag

  In its classical genomic mode of action, the aryl hydrocarbon receptor (AhR) acts as a ligand activated transcription factor regulating expression of target genes such as CYP1A1 and CYP1B1. Some ligands may also trigger more rapid nongenomic responses through AhR, including calcium signaling (Ca2+). In the present study we observed that pyrene induced a relatively rapid increase in intracellular Ca2+-concentrations ([Ca2+]i) in human microvascular endothelial cells (HMEC-1) and human embryonic kidney cells (HEK293) that was attenuated by AhR-inhibitor treatment and/or transient AhR knockdown by RNAi. In silico molecular docking based on homology models, suggested that pyrene is not able to bind to the human AhR in the agonist conformation. Instead, pyrene docked in the antagonist conformation of the AhR PAS-B binding pocket, although the interaction differed from antagonists such as GNF-351 and CH223191. Accordingly, pyrene did not induce CYP1A1 or CYP1B1, but suppressed CYP1-expression by benzo[a]pyrene (B[a]P) in HMEC-1 cells, confirming that pyrene act as an antagonist of AhR-induced gene expression. Use of pharmacological inhibitors and Ca2+-free medium indicated that the pyrene-induced AhR nongenomic [Ca2+]i increase was initiated by Ca2+-release from intracellular stores followed by a later phase of extracellular Ca2+-influx, consistent with store operated calcium entry (SOCE). These effects was accompanied by an AhR-dependent reduction in ordered membrane lipid domains, as determined by di-4-ANEPPDHQ staining. Addition of cholesterol inhibited both the pyrene-induced [Ca2+]i-increase and alterations in membrane lipid order. In conclusion, we propose that pyrene binds to AhR, act as an antagonist of the canonical genomic AhR/Arnt/CYP1-pathway, reduces ordered membrane lipid domains, and activates AhR nongenomic Ca2+-signaling from intracellular stores.

• Becher, Rune; Øvrevik, Johan; Schwarze, Per Everhard; Nilsen, Steinar Klubben; Hongslo, Jan Kenneth & Bakke, Jan Vilhelm (2018). Do carpets impair indoor air quality and cause adverse health outcomes: a review. International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 15(2). doi: 10.3390/ijerph15020184. Fulltekst i vitenarkiv Vis sammendrag

  Several earlier studies have shown the presence of more dust and allergens in carpets compared with non-carpeted floors. At the same time, adverse effects of carpeted floors on perceived indoor air quality as well as worsening of symptoms in individuals with asthma and allergies were reported. Avoiding extensive carpet use in offices, schools, kindergartens and bedrooms has therefore been recommended by several health authorities. More recently, carpet producers have argued that former assessments were obsolete and that modern rugs are unproblematic, even for those with asthma and allergies. To investigate whether the recommendation to be cautious with the use of carpets is still valid, or whether there are new data supporting that carpet flooring do not present a problem for indoor air quality and health, we have reviewed the literature on this matter. We have not found updated peer reviewed evidence that carpeted floor is unproblematic for the indoor environment. On the contrary, also more recent data support that carpets may act as a repository for pollutants which may become resuspended upon activity in the carpeted area. Also, the use of carpets is still linked to perception of reduced indoor air quality as well as adverse health effects as previously reported. To our knowledge, there are no publications that report on deposition of pollutants and adverse health outcomes associated with modern rugs. However, due to the three-dimensional structure of carpets, any carpet will to some extent act like a sink. Thus, continued caution should still be exercised when considering the use of wall-to-wall carpeted floors in schools, kindergartens and offices, as well as in children’s bedrooms unless special needs indicate that carpets are preferable

• Dziendzikowska, K; Gajewska, Malgorzata; Wilczak, Jacek; Mruk, R; Oczkowski, Michał & Żyła, Ewa [Vis alle 14 forfattere av denne artikkelen] (2018). The effects of 1st and 2nd generation biodiesel exhaust exposure on hematological and biochemical blood indices of Fisher344 male rats – The FuelHealth project. Environmental Toxicology and Pharmacology. ISSN 1382-6689. 63, s. 34–47. doi: 10.1016/j.etap.2018.08.001. Fulltekst i vitenarkiv
• Valand, Renate; Magnusson, Pål Amdal; Dziendzikowska, Katarzyna; Gajewska, Malgorzata; Wilczak, Jacek & Oczkowski, Michał [Vis alle 17 forfattere av denne artikkelen] (2018). Gene expression changes in rat brain regions after 7- and 28 days inhalation exposure to exhaust emissions from 1st and 2nd generation biodiesel fuels - The FuelHealth project. Inhalation Toxicology. ISSN 0895-8378. 30(7-8), s. 299–312. doi: 10.1080/08958378.2018.1520370. Fulltekst i vitenarkiv
• Myhre, Oddvar; Låg, Marit; Villanger, Gro Dehli; Oftedal, Bente Margaret; Øvrevik, Johan & Holme, Jørn Andreas [Vis alle 10 forfattere av denne artikkelen] (2018). Early life exposure to air pollution particulate matter (PM) as risk factor for attention deficit/hyperactivity disorder (ADHD): Need for novel strategies for mechanisms and causalities. Toxicology and Applied Pharmacology. ISSN 0041-008X. 354, s. 196–214. doi: 10.1016/j.taap.2018.03.015. Fulltekst i vitenarkiv
• Budnik, Lygia Therese; Adam, Balazs; Albin, Maria; Banelli, Barbara; Baur, Xaver & Belpoggi, Fiorella [Vis alle 25 forfattere av denne artikkelen] (2018). Diagnosis, monitoring and prevention of exposure-related non-communicable diseases in the living and working environment: DiMoPEx-project is designed to determine the impacts of environmental exposure on human health. Journal of Occupational Medicine and Toxicology. 13. doi: 10.1186/s12995-018-0186-9. Fulltekst i vitenarkiv
• Longhin, Eleonora; Holme, Jørn Andreas; Gualtieri, Maurizio; Camatini, Marina & Øvrevik, Johan (2018). Milan winter fine particulate matter (wPM2.5) induces IL-6 and IL-8 synthesis in human bronchial BEAS-2B cells, but specifically impairs IL-8 release. Toxicology in Vitro. ISSN 0887-2333. 52, s. 365–373. doi: 10.1016/j.tiv.2018.07.016. Fulltekst i vitenarkiv
• Brinchmann, Bendik Christian; Skuland, Tonje Schwach; Rambøl, Mia Marie-Elisabeth; Szöke, Krisztina; Brinchmann, Jan E. & Gutleb, Arno C. [Vis alle 16 forfattere av denne artikkelen] (2018). Lipophilic components of diesel exhaust particles induce pro-inflammatory responses in human endothelial cells through AhR dependent pathway(s). Particle and Fibre Toxicology. 15. doi: 10.1186/s12989-018-0257-1. Fulltekst i vitenarkiv Vis sammendrag

  Background Exposure to traffic-derived particulate matter (PM), such as diesel exhaust particles (DEP), is a leading environmental cause of cardiovascular disease (CVD), and may contribute to endothelial dysfunction and development of atherosclerosis. It is still debated how DEP and other inhaled PM can contribute to CVD. However, organic chemicals (OC) adhered to the particle surface, are considered central to many of the biological effects. In the present study, we have explored the ability of OC from DEP to reach the endothelium and trigger pro-inflammatory reactions, a central step on the path to atherosclerosis. Results Exposure-relevant concentrations of DEP (0.12 μg/cm2) applied on the epithelial side of an alveolar 3D tri-culture, rapidly induced pro-inflammatory and aryl hydrocarbon receptor (AhR)-regulated genes in the basolateral endothelial cells. These effects seem to be due to soluble lipophilic constituents rather than particle translocation. Extractable organic material of DEP (DEP-EOM) was next fractionated with increasing polarity, chemically characterized, and examined for direct effects on pro-inflammatory and AhR-regulated genes in human microvascular endothelial (HMEC-1) cells and primary human endothelial cells (PHEC) from four healthy donors. Exposure-relevant concentrations of lipophilic DEP-EOM (0.15 μg/cm2) induced low to moderate increases in IL-1α, IL-1β, COX2 and MMP-1 gene expression, and the MMP-1 secretion was increased. By contrast, the more polar EOM had negligible effects, even at higher concentrations. Use of pharmacological inhibitors indicated that AhR and protease-activated receptor-2 (PAR-2) were central in regulation of EOM-induced gene expression. Some effects also seemed to be attributed to redox-responses, at least at the highest exposure concentrations tested. Although the most lipophilic EOM, that contained the majority of PAHs and aliphatics, had the clearest low-concentration effects, there was no straight-forward link between chemical composition and biological effects. Conclusion Lipophilic and semi-lipophilic chemicals seemed to detach from DEP, translocate through alveolar epithelial cells and trigger pro-inflammatory reactions in endothelial cells at exposure-relevant concentrations. These effects appeared to be triggered by AhR agonists, and involve PAR-2 signaling.

• Kowalska, Magdalena; Wegierek-Ciuk, Aneta; Brzoska, Kamil; Wojewódzka, Maria; Meczynska-Wielgosz, Sylwia & Gromadzka-Ostrowska, Joanna [Vis alle 10 forfattere av denne artikkelen] (2017). Genotoxic potential of diesel exhaust particles from the combustion of first- and second-generation biodiesel fuels-the FuelHealth project. Environmental Science and Pollution Research. ISSN 0944-1344. 24(31), s. 24223–24234. doi: 10.1007/s11356-017-9995-0. Fulltekst i vitenarkiv Vis sammendrag

  Epidemiological data indicate that exposure to diesel exhaust particles (DEPs) from traffic emissions is associated with higher risk of morbidity and mortality related to cardiovascular and pulmonary diseases, accelerated progression of atherosclerotic plaques, and possible lung cancer. While the impact of DEPs from combustion of fossil diesel fuel on human health has been extensively studied, current knowledge of DEPs from combustion of biofuels provides limited and inconsistent information about its mutagenicity and genotoxicity, as well as possible adverse health risks. The objective of the present work was to compare the genotoxicity of DEPs from combustion of two first-generation fuels, 7% fatty acid methyl esters (FAME) (B7) and 20% FAME (B20), and a second-generation 20% FAME/hydrotreated vegetable oil (SHB: synthetic hydrocarbon biofuel) fuel. Our results revealed that particulate engine emissions from each type of biodiesel fuel induced genotoxic effects in BEAS-2B and A549 cells, manifested as the in-creased levels of single-strand breaks, the increased frequencies of micronuclei, or the deregulated expression of genes involved in DNA damage signaling pathways. We also found that none of the tested DEPs showed the induction of oxidative DNA damage and the gamma-H2AX-detectable double-strand breaks. The most pronounced differences concerning the tested particles were observed for the induction of single-strand breaks, with the greatest genotoxicity being associated with the B7-derived DEPs. The differences in other effects between DEPs from the different biodiesel blend percentage and biodiesel feedstock were also observed, but the magnitude of these variations was limited.

• Skuland, Tonje Schwach; Refsnes, Magne Arnold; Magnusson, Pål Amdal; Oczkowski, Michal; Gromadzka-Ostrowska, Joanna & Kruszewski, Marcin [Vis alle 10 forfattere av denne artikkelen] (2017). Proinflammatory effects of diesel exhaust particles from moderate blend concentrations of 1st and 2nd generation biodiesel in BEAS-2B bronchial epithelial cells-The FuelHealth project. Environmental Toxicology and Pharmacology. ISSN 1382-6689. 52, s. 138–142. doi: 10.1016/j.etap.2017.04.004. Fulltekst i vitenarkiv Vis sammendrag

  Biodiesel fuel fuels are introduced at an increasing extent as a more carbon-neutral alternative to reduce CO2-emissions, compared to conventional diesel fuel. In the present study we have investigated the impact of increasing the use of 1st generation fatty acid methyl ester (FAME) biodiesel from current 7% blend (B7) to 20% blend (B20), or by increasing the biodiesel content by adding 2nd generation hydrotreated vegetable oil (HVO) based biodiesel (SHB; Synthetic Hydrocarbon Biofuel) on toxicity of diesel exhaust particles (DEP) in an in vitro system. Human bronchial epithelial BEAS-25 cells were exposed for 4 and 20 h to DEP from B7, B20 and SHB at different concentrations, and examined for effects on gene expression of interleukin 6 (IL-6), CXCL8 (IL-8), CYP1A1 and heme oxygenase-1 (HO-1). The results show that both B20 and SHB were more potent inducers of IL-6 expression compared to B7. Only B20 induced statistically significant increases in CXCL8 expression. By comparison the rank order of potency to induce CYP1A1 was SHB > B7 > B20. No statistically significant difference were observed form HO-1 expression, suggesting that the differences in cytokine responses were not due to oxidative stress. The results show that even moderate increases in biodiesel blends, from 7% to 20%, may increase the proinflammatory potential of emitted DEP in BEAS-2B cells. This effect was observed for both addition of 1st generation FAME and 2nd generation HVO biodiesel.

• Magnusson, Pål Amdal; Oczkowski, Michał; Øvrevik, Johan; Gajewska, Malgorzata; Wilczak, Jacek & Biedrzycki, Jacek [Vis alle 16 forfattere av denne artikkelen] (2017). No adverse lung effects of 7- and 28-day inhalation exposure of rats to emissions from petrodiesel fuel containing 20% rapeseed methyl esters (B20) with and without particulate filter - the FuelHealth project. Inhalation Toxicology. ISSN 0895-8378. 29(5), s. 206–218. doi: 10.1080/08958378.2017.1339149. Fulltekst i vitenarkiv
• Becher, Rune; Høie, Anja Hortemo; Bakke, Jan Vilhelm; Holøs, Sverre Bjørn & Øvrevik, Johan (2017). Dampness and Moisture Problems in Norwegian Homes. International Journal of Environmental Research and Public Health (IJERPH). ISSN 1661-7827. 14(10). doi: 10.3390/ijerph14101241. Fulltekst i vitenarkiv Vis sammendrag

  The occurrence of dampness and mold in the indoor environment is associated with respiratory-related disease outcomes. Thus, it is pertinent to know the magnitude of such indoor environment problems to be able to estimate the potential health impact in the population. In the present study, the moisture damage in 10,112 Norwegian dwellings was recorded based on building inspection reports. The levels of moisture damage were graded based on a condition class (CC), where CC0 is immaculate and CC1 acceptable (actions not required), while CC2 and CC3 indicate increased levels of damage that requires action. Of the 10,112 dwellings investigated, 3125 had verified moisture or mold damage. This amounts to 31% of the surveyed dwellings. Of these, 27% had CC2 as the worst grade, whereas 4% had CC3 as the worst grade level. The room types and building structures most prone to moisture damage were (in rank order) crawl spaces, basements, un-insulated attics, cooling rooms, and bathrooms. The high proportion of homes with moisture damage indicate a possible risk for respiratory diseases in a relatively large number of individuals, even if only the more extensive moisture damages and those located in rooms where occupants spend the majority of their time would have a significant influence on adverse health effects

• Øvrevik, Johan; Refsnes, Magne; Låg, Marit; Brinchmann, Bendik Christian; Schwarze, Per E & Holme, Jørn Andreas (2017). Triggering mechanisms and Inflammatory effects of combustion exhaust particles with implication for carcinogenesis. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 121, s. 55–62. doi: 10.1111/bcpt.12746. Fulltekst i vitenarkiv
• Lankoff, Anna; Brzoska, Kamil; Czarnocka, Joanna; Kowalska, Magdalena; Lisowska, Halina & Mruk, Remigiusz [Vis alle 10 forfattere av denne artikkelen] (2017). A comparative analysis of in vitro toxicity of diesel exhaust particles from combustion of 1st-and 2nd-generation biodiesel fuels in relation to their physicochemical properties-the FuelHealth project. Environmental Science and Pollution Research. ISSN 0944-1344. 24(23), s. 19357–19374. doi: 10.1007/s11356-017-9561-9. Fulltekst i vitenarkiv Vis sammendrag

  Biodiesels represent more carbon-neutral fuels and are introduced at an increasing extent to reduce emission of greenhouse gases. However, the potential impact of different types and blend concentrations of biodiesel on the toxicity of diesel engine emissions are still relatively scarce and to some extent contradictory. The objective of the present work was to compare the toxicity of diesel exhaust particles (DEP) from combustion of two 1st-generation fuels: 7% fatty acid methyl esters (FAME; B7) and 20% FAME (B20) and a 2nd-generation 20% FAME/HVO (synthetic hydrocarbon biofuel (SHB)) fuel. Our findings indicate that particulate emissions of each type of biodiesel fuel induce cytotoxic effects in BEAS-2B and A549 cells, manifested as cell death (apoptosis or necrosis), decreased protein concentrations, intracellular ROS production, as well as increased expression of antioxidant genes and genes coding for DNA damage-response proteins. The different biodiesel blend percentages and biodiesel feedstocks led to marked differences in chemical composition of the emitted DEP. The different DEPs also displayed statistically significant differences in cytotoxicity in A549 and BEAS-2B cells, but the magnitude of these variations was limited. Overall, it seems that increasing biodiesel blend concentrations from the current 7 to 20% FAME, or substituting 1st-generation FAME biodiesel with 2nd-generation HVO biodiesel (at least below 20% blends), affects the in vitro toxicity of the emitted DEP to some extent, but the biological significance of this may be moderate.

• Ferrec, Eric Le & Øvrevik, Johan (2017). G-protein coupled receptors (GPCR) and environmental exposure. Consequences for cell metabolism using the β-adrenoceptors as example. Current Opinion in Toxicology. ISSN 2468-2020. 8, s. 14–19. doi: 10.1016/j.cotox.2017.11.012. Fulltekst i vitenarkiv
• Longhin, Eleonora; Gualtieri, Maurizio; Capasso, Lauro; Bengalli, Rossella; Mollerup, Steen Kristen & Holme, Jørn Andreas [Vis alle 11 forfattere av denne artikkelen] (2016). Physico-chemical properties and biological effects of diesel and biomass particles. Environmental Pollution (1987). ISSN 0269-7491. 215, s. 366–375. doi: 10.1016/j.envpol.2016.05.015. Fulltekst i vitenarkiv Vis sammendrag

  Diesel combustion and solid biomass burning are the major sources of ultrafine particles (UFP) in urbanized areas. Cardiovascular and pulmonary diseases, including lung cancer, are possible outcomes of combustion particles exposure, but differences in particles properties seem to influence their biological effects. Here the physico-chemical properties and biological effects of diesel and biomass particles, produced under controlled laboratory conditions, have been characterized. Diesel UFP were sampled from a Euro 4 light duty vehicle without DPF fuelled by commercial diesel and run over a chassis dyno. Biomass UFP were collected from a modern automatic 25 kW boiler propelled by prime quality spruce pellet. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images of both diesel and biomass samples showed aggregates of soot particles, but in biomass samples ash particles were also present. Chemical characterization showed that metals and PAHs total content was higher in diesel samples compared to biomass ones. Human bronchial epithelial (HBEC3) cells were exposed to particles for up to 2 weeks. Changes in the expression of genes involved in xenobiotic metabolism were observed after exposure to both UFP already after 24 h. However, only diesel particles modulated the expression of genes involved in inflammation, oxidative stress and epithelial-to-mesenchymal transition (EMT), increased the release of inflammatory mediators and caused phenotypical alterations, mostly after two weeks of exposure. These results show that diesel UFP affected cellular processes involved in lung and cardiovascular diseases and cancer. Biomass particles exerted low biological activity compared to diesel UFP. This evidence emphasizes that the study of different emission sources contribution to ambient PM toxicity may have a fundamental role in the development of more effective strategies for air quality improvement.

• Låg, Marit; Øvrevik, Johan; Totlandsdal, Annike Irene; Lilleaas, Edel; Thormodsæter, Anders & Holme, Jørn Andreas [Vis alle 8 forfattere av denne artikkelen] (2016). Air pollution-related metals induce differential cytokine responses in bronchial epithelial cells. Toxicology in Vitro. ISSN 0887-2333. 36, s. 53–65. doi: 10.1016/j.tiv.2016.07.004. Fulltekst i vitenarkiv
• Bach, Nicolai S; Bølling, Anette Kocbach; Brinchmann, Bendik Christian; Totlandsdal, Annike Irene; Skuland, Tonje Schwach & Holme, Jørn Andreas [Vis alle 9 forfattere av denne artikkelen] (2015). Cytokine responses induced by diesel exhaust particles are suppressed by PAR-2 silencing and antioxidant treatment, and driven by polar and non-polar soluble constituents. Toxicology Letters. ISSN 0378-4274. 238(2), s. 72–82. doi: 10.1016/j.toxlet.2015.07.002. Fulltekst i vitenarkiv
• Øvrevik, Johan; Refsnes, Magne; Låg, Marit; Holme, Jørn Andreas & Schwarze, Per E (2015). Activation of proinflammatory responses in cells of the airway mucosa by particulate matter: Oxidant- and non-oxidant-mediated triggering mechanisms. Biomolecules. 5(3), s. 1399–1440. doi: 10.3390/biom5031399. Fulltekst i vitenarkiv
• Bach, Nicolai S; Låg, Marit & Øvrevik, Johan (2014). Toll like receptor-3 priming alters diesel exhaust particle-induced cytokine responses in human bronchial epithelial cells. Toxicology Letters. ISSN 0378-4274. 228(1), s. 42–47. doi: 10.1016/j.toxlet.2014.03.021. Fulltekst i vitenarkiv
• Holme, Jørn Andreas; Nyvold, Hannah Elise; Tat, V; Arlt, V M; Bhargava, A & Gutzkow, Kristine Bjerve [Vis alle 13 forfattere av denne artikkelen] (2014). Mechanisms linked to differences in the mutagenic potential of 1,3-dinitropyrene and 1,8-dinitropyrene. Toxicology reports. 1, s. 459–473. doi: 10.1016/j.toxrep.2014.07.009. Fulltekst i vitenarkiv
• Mayati, A; Ferrec, E Le; Holme, JA; Fardel, O; Lagadic-Gossmann, D & Øvrevik, Johan (2014). Calcium signaling and β2-adrenergic receptors regulate 1-nitropyrene induced CXCL8 responses in BEAS-2B cells. Toxicology in Vitro. ISSN 0887-2333. 28(6), s. 1153–1157. doi: 10.1016/j.tiv.2014.05.012. Fulltekst i vitenarkiv
• Totlandsdal, Annike Irene; Øvrevik, Johan; Cocheran, Richard; Herseth, Jan Inge; Bølling, Anette Kocbach & Låg, Marit [Vis alle 10 forfattere av denne artikkelen] (2014). The occurrence of polycyclic aromatic hydrocarbons and their derivatives and the proinflammatory potential of fractionated extracts of diesel exhaust and wood smoke particles. Journal of Environmental Science and Health. Part A: Toxic/Hazardous Substances and Environmental Engineering. ISSN 1093-4529. 49(4), s. 383–396. doi: 10.1080/10934529.2014.854586. Fulltekst i vitenarkiv Vis sammendrag

  Exposure to combustion emissions, including diesel engine exhaust and wood smoke particles (DEPs and WSPs), has been associated with inflammatory responses. To investigate the possible role of polycyclic aromatic hydrocarbons (PAHs) and PAH-derivatives, the DEPs and WSPs methanol extracts were fractionated by solid phase extraction (SPE), and the fractions were analyzed for more than ~120 compounds. The pro-inflammatory effects of the fractionated extracts were characterized by exposure of bronchial epithelial lung cells (BEAS-2B). Both native DEPs and WSPs caused a concentration-dependent increase in IL-6 and IL-8 release and cytotoxicity. This is consistent with the finding of a rather similar total content of PAHs and PAH-derivatives. Yet, the samples differed in specific components, suggesting that different species contribute to the toxicological response in these two types of particles. The majority of the IL-6 release and cytotoxicity was induced upon exposure to the most polar (methanol) SPE fraction of extracts from both samples. In these fractions hydroxy-PAHs, carboxy-PAHs were observed along with nitro-amino-PAHs in DEP. However, the biological effects induced by the polar fractions could not be attributed only to the occurrence of PAH-derivatives. The present findings indicate a need for further characterization of organic extracts, beyond an extensive analysis of commonly suspected PAH and PAH-derivatives.

• Refsnes, Magne; Skuland, Tonje Schwach; Låg, Marit; Schwarze, Per E & Øvrevik, Johan (2014). Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL 8 (IL-8) induction in lung epithelial cells. Journal of Inflammation Research. 7, s. 169–185. doi: 10.2147/JIR.S69646. Fulltekst i vitenarkiv
• Skuland, Tonje Schwach; Øvrevik, Johan; Låg, Marit & Refsnes, Magne (2014). Role of size and surface area for pro-inflammatory responses to silica nanoparticles in epithelial lung cells: importance of exposure conditions. Toxicology in Vitro. ISSN 0887-2333. 28(2), s. 146–155. doi: 10.1016/j.tiv.2013.10.018. Fulltekst i vitenarkiv
• Skuland, Tonje Schwach; Øvrevik, Johan; Låg, Marit; Schwarze, Per E & Refsnes, Magne (2014). Silica nanoparticles induce cytokine responses in lung epithelial cells through activation of a p38/TACE/TGF-α/EGFR-pathway and NF-κΒ signalling. Toxicology and Applied Pharmacology. ISSN 0041-008X. 279(1), s. 76–86. doi: 10.1016/j.taap.2014.05.006. Fulltekst i vitenarkiv
• Øvrevik, Johan; Låg, Marit; Lecureur, Valerie; Gilot, David; Lagadic-Gossmann, Dominique & Refsnes, Magne [Vis alle 10 forfattere av denne artikkelen] (2014). AhR and Arnt differentially regulate NF-κB signaling and chemokine responses in human bronchial epithelial cells. Cell Communication and Signaling. 12(1). doi: 10.1186/s12964-014-0048-8. Fulltekst i vitenarkiv
• Øvrevik, Johan; Refsnes, Magne; Holme, Jørn Andreas; Schwarze, Per E & Låg, Marit (2013). Mechanisms of chemokine responses by polycyclic aromatic hydrocarbons in bronchial epithelial cells: sensitization through toll-like receptor-3 priming. Toxicology Letters. ISSN 0378-4274. 219(2), s. 125–132. doi: 10.1016/j.toxlet.2013.02.014. Fulltekst i vitenarkiv
• Schwarze, Per E; Totlandsdal, Annike Irene; Låg, Marit; Refsnes, Magne; Holme, Jørn Andreas & Øvrevik, Johan (2013). Inflammation-Related Effects of Diesel Engine Exhaust Particles: Studies on Lung Cells In Vitro. Biomedical Research. ISSN 0388-6107. doi: 10.1155/2013/685142. Fulltekst i vitenarkiv
• Øvrevik, Johan; Holme, Jørn Andreas; Låg, Marit; Schwarze, Per E & Refsnes, Magne (2013). Differential chemokine induction by 1-nitropyrene and 1-aminopyrene in bronchial epithelial cells: Importance of the TACE/TGF-alpha/EGFR-pathway. Environmental Toxicology and Pharmacology. ISSN 1382-6689. 35(2), s. 235–239. doi: 10.1016/j.etap.2012.12.011. Fulltekst i vitenarkiv
• Totlandsdal, Annike Irene; Herseth, Jan Inge; Bølling, Anette Kocbach; Kubatova, Alena; Braun, Artur & Cochran, Richard E. [Vis alle 9 forfattere av denne artikkelen] (2012). Differential effects of the particle core and organic extract of diesel exhaust particles. Toxicology Letters. ISSN 0378-4274. 208(3), s. 262–268. doi: 10.1016/j.toxlet.2011.10.025. Fulltekst i vitenarkiv
• Bølling, Anette Kocbach; Øvrevik, Johan; Samuelsen, Jan Tore; Holme, Jørn Andreas; Rakkestad, Kirsten Eline & Mathisen, Gro Haarklou [Vis alle 9 forfattere av denne artikkelen] (2012). Mono-2-ethylhexylphthalate (MEHP) induces TNF-alpha release and macrophage differentiation through different signalling pathways in RAW264.7 cells. Toxicology Letters. ISSN 0378-4274. 209(1), s. 43–50. doi: 10.1016/j.toxlet.2011.11.016. Fulltekst i vitenarkiv
• Øya, Elisabeth; Øvrevik, Johan; Arlt, Volker M; Nagy, Eszter; Phillips, David H & Holme, Jørn Andreas (2011). DNA damage and DNA damage response in human bronchial epithelial BEAS-2B cells following exposure to 2-nitrobenzanthrone and 3-nitrobenzanthrone: role in apoptosis. Mutagenesis. ISSN 0267-8357. 26(6), s. 697–708. doi: 10.1093/mutage/ger035. Fulltekst i vitenarkiv
• Gualtieri, Maurizio; Øvrevik, Johan; Mollerup, Steen Kristen; Asare, Nana; Longhin, Eleonora & Dahlman, Hans-Jørgen [Vis alle 8 forfattere av denne artikkelen] (2011). Airborne urban particles (Milan winter-PM2.5) cause mitotic arrest and cell death: Effects on DNA, mitochondria, AhR binding and spindle organization. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. ISSN 0027-5107. 713(1-2), s. 18–31. doi: 10.1016/j.mrfmmm.2011.05.011. Fulltekst i vitenarkiv Vis sammendrag

  Airborne particulate matter (PM) is considered to be an important contributor to lung diseases. In the present study we report that Milan winter-PM2.5 inhibited proliferation in human bronchial epithelial cells (BEAS-2B) by inducing mitotic arrest. The cell cycle arrest was followed by an increase in mitotic-apoptotic cells, mitotic slippage and finally an increase in “classical” apoptotic cells. Exposure to winter-PM10 induced only a slight effect which may be due to the presence of PM2.5 in this fraction while pure combustion particles failed to disturb mitosis. Fewer cells expressing the mitosis marker phospho-histone H3 compared to cells with condensed chromosomes, suggest that PM2.5 induced premature mitosis. PM2.5 was internalized into the cells and often localized in laminar organelles, although particles without apparent plasma membrane covering were also seen. In PM-containing cells mitochondria and lysosomes were often damaged, and in mitotic cells fragmented chromosomes often appeared. PM2.5 induced DNA strands breaks and triggered a DNA-damage response characterized by increased phosphorylation of ATM, Chk2 and H2AX; as well as induced a marked increase in expression of the aryl hydrocarbon receptor (AhR)-regulated genes, CYP1A1, CYP1B1 and AhRR. Furthermore, some disturbance of the organization of microtubules was indicated. It is hypothesized that the induced mitotic arrest and following cell death was due to a premature chromosome condensation caused by a combination of DNA, mitochondrial and spindle damage.

• Øvrevik, Johan; Refsnes, Magne; Totlandsdal, Annike Irene; Holme, Jørn Andreas; Schwarze, Per E & Låg, Marit (2011). TACE/TGF-a/EGFR regulates CXCL8 in bronchial epithelial cells exposed to particulate matter components. European Respiratory Journal. ISSN 0903-1936. 38(5), s. 1189–1199. doi: 10.1183/09031936.00171110. Fulltekst i vitenarkiv
• Øvrevik, Johan; Arlt, VM; Øya, E; Nagy, E; Mollerup, Steen Kristen & Phillips, DH [Vis alle 8 forfattere av denne artikkelen] (2010). Differential effects of nitro-PAHs and amino-PAHs on cytokine and chemokine responses in human bronchial epithelial BEAS-2B cells. Toxicology and Applied Pharmacology. ISSN 0041-008X. 242(3), s. 270–280. doi: 10.1016/j.taap.2009.10.017. Fulltekst i vitenarkiv Vis sammendrag

  Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are found in diesel exhaust and air pollution particles. Along with other PAHs, many nitro-PAHs possess mutagenic and carcinogenic properties, but their effects on pro-inflammatory processes and cell death are less known. In the present study we examined the effects of 1-nitropyrene (1-NP), 3-nitrofluoranthene (3-NF) and 3-nitrobenzanthrone (3-NBA) and their corresponding amino forms, 1-AP, 3-AF and 3-ABA, in human bronchial epithelial BEAS-2B cells. The effects of the different nitro- and amino-PAHs were compared to the well-characterized PAH benzo[a]pyrene (B[a]P). Expression of 17 cytokine and chemokine genes, measured by real-time PCR, showed that 1-NP and 3-NF induced a completely different cytokine/chemokine gene expression pattern to that of their amino analogues. 1-NP/3-NF-induced responses were dominated by maximum effects on CXCL8 (IL-8) and TNF-α expression, while 1-AP-/3-AF-induced responses were dominated by CCL5 (RANTES) and CXCL10 (IP-10) expression. 3-NBA and 3-ABA induced only marginal cytokine/chemokine responses. However, 3-NBA exposure induced considerable DNA damage resulting in accumulation of cells in S-phase and a marked increase in apoptosis. B[a]P was the only compound to induce expression of aryl hydrocarbon receptor (AhR)-regulated genes, such as CYP1A1 and CYP1B1, but did not induce cytokine/chemokine responses in BEAS-2B cells. Importantly, nitro-PAHs and amino-PAHs induced both qualitatively and quantitatively different effects on cytokine/chemokine expression, DNA damage, cell cycle alterations and cytotoxicity. The cytokine/chemokine responses appeared to be triggered, at least partly, through mechanisms separate from the other examined endpoints. These results confirm and extend previous studies indicating that certain nitro-PAHs have a considerable pro-inflammatory potential.

• Schwarze, Per E; Totlandsdal, Annike Irene; Herseth, Jan Inge; Holme, Jørn Andreas; Låg, Marit & Refsnes, Magne [Vis alle 9 forfattere av denne artikkelen] (2010). Importance of sources and components of particulate air pollution for cardio-pulmonary inflammatory responses. I Villanyi, Vanda (Red.), Air pollution. Sciyo. ISSN 9789533071435. s. 47–73. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Folkehelseinstituttet; Berstad, Paula Marianna; Helleve, Arnfinn; Indseth, Thor; Kløvstad, Hilde & Knudsen, Ann Kristin Skrindo [Vis alle 8 forfattere av denne artikkelen] (2026). Temautgave av Folkehelserapporten: De viktigste folkehelseutfordringene. Fulltekst i vitenarkiv Vis sammendrag

  I denne rapporten gir FHI en oversikt over helsetilstanden i Norge, og faktorer som påvirker den. Vi går gjennom både overordnede samfunnsforhold, store folkehelseutfordringer, og helsetrusler. Noen særlig viktige samfunnsforhold som har stor påvirkning på folkehelsen i dag og framover, er at vi har en aldrende befolkning, som setter press på helsetjenestene og samfunnets bærekraft både ved at antallet eldre øker, og at andelen øker opp mot den arbeidsføre befolkningen. Sosial ulikhet i helse er fortsatt en folkehelseutfordring og blir ytterligere komplisert av innvandring. Svekket internasjonalt samarbeid om beredskap, en urolig geopolitisk situasjon, digitalisering av samfunnet og endrede holdninger til kunnskap påvirker folkehelsearbeidet i Norge. Folkehelsen og livskvaliteten i Norge er god. Vi lever lenge og andelen friske leveår har økt. Lengre levetid bidrar imidlertid til at år levd med helsetap også øker. Ikke-smittsomme sykdommer er hovedårsaken til sykdomsbyrden i Norge. Vi trekker i denne rapporten særlig fram to utfordringer: Psykiske lidelser blant barn og unge har økt, særlig etter 2010, og fortsetter å øke. Dette påvirker livskvalitet gjennom hele livsløpet, og samfunnsdeltakelse i utdanning og arbeidsliv. Sosiale ulikheter forsterker disse effektene. Tidlig forebygging av psykiske lidelser hos unge kan gi store gevinster for samfunnsdeltakelse og folkehelse. En annen utfordring er sykdom i en aldrende befolkning. En stadig høyere andel lever mange år med sykdom, og oftere med flere sykdommer, hvor hjerte- og karsykdommer, kreft og demens utgjør en vesentlig del. Flere av sykdommene innenfor disse hovedgruppene er i stor grad forebyggbare. Framskrivninger av norske helseutgifter viser at demens, hjerneslag og diabetes vil være de viktigste kostnadsdriverne fram mot 2050. Helsetrusler omfatter både akutte hendelser og langsiktige utviklingstrekk som kan påvirke folkehelsen. De viktigste truslene fremover er komplekse og henger sammen med globale endringer. Pandemier og smittsomme sykdommer vil fortsatt kunne være store utfordringer, forsterket av blant annet global mobilitet, urbanisering og svekket internasjonalt samarbeid. Antimikrobiell resistens (AMR) er en langsomt voksende trussel som kan gjøre behandling av infeksjoner vanskelig og true moderne medisinsk praksis. Forhold som svekker vaksinasjonsdekning kan bidra til økt risiko for utbrudd av alvorlige smittsomme sykdommer, flere sykehusinnleggelser, høyere dødelighet og økt antibiotikabruk. Ellers trekker vi også fram sårbarhet knyttet til drikkevann, faren for kjemikaliehendelser og syntetisk biologi som trusler som krever god beredskapsevne. Klimaendringer er vurdert som en forsterker av andre trusler. Det ligger store muligheter i å forebygge uhelse. Forebygging er den mest kostnadseffektive strategien for å redusere sykdomsbyrden. Det er behov for å styrke kunnskapen om effektive folkehelsetiltak og forebyggende tiltak i helsetjenestene. For en stor del av sykdomsbyrden er de underliggende risikofaktorene ikke kjent eller forstått, og her ligger det potensial for å forebygge sykdom gjennom å skaffe kunnskap om risiko- og årsaksfaktorer. God overvåking og beredskap, internasjonalt og tverrsektorielt samarbeid og forebyggende tiltak er avgjørende for å holde forekomsten av smittsomme sykdommer lav og redusere konsekvensene av helsetrusler. Fremtidens folkehelsearbeid må styrke den tverrsektorielle tilnærmingen og se på etablerte utfordringer og akutte helsetrusler i sammenheng.

• Mariussen, Espen; Skuland, Tonje Schwach; Dahlman, Hans Jørgen; Låg, Marit & Øvrevik, Johan (2023). An Approach to Test Effects on Secondary Organs via Lung Cells Exposed at the Air Liquid Interphase. Annals of Work Exposures and Health. ISSN 2398-7308. 67(S1), s. i59–i59. Fulltekst i vitenarkiv
• Moazami, Therese Nitter; Hilt, Bjørn; Sørås, Kirsti; Svendsen, Kristin V Hirsch; Refsnes, Magne Arnold & Dahlman, Hans Jørgen [Vis alle 9 forfattere av denne artikkelen] (2022). Korttidseksponering for steinmineraler brukt i asfalt kan påvirke lungefunksjonog lungeinflammasjon hos friske, unge mennesker. Yrkeshygienikeren. ISSN 0802-2763. Fulltekst i vitenarkiv
• Hak, Claudia; Øvrevik, Johan; Låg, Marit & Waaler, Ingrid Emilie (2021). Ny forskning viser sammenheng mellom svevestøv og astma hos barn – nivået måles ikke. [Internet]. www.nrk.no. Fulltekst i vitenarkiv
• Guerreiro, Cristina; Øvrevik, Johan; Solheim, Pernille & Garden, Vemund Anke (2020). Ber om fortgang i forskning på corona og luftforurensning. [Journal]. www.vg.no. Fulltekst i vitenarkiv
• Holme, Jørn Andreas; Låg, Marit; Øvrevik, Johan & Golestani, Karan (2020). Kan luftforurensning øke risikoen for covid-19? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 140(18), s. 1–3. doi: 10.4045/tidsskr.20.0843. Fulltekst i vitenarkiv
• Suren, Pål; Holt, Tonje; Wang, Mari Vaage; Bye, Elin Kristin; Brandlistuen, Ragnhild Eek & Helland, Maren Sand [Vis alle 10 forfattere av denne artikkelen] (2018). Barn og unges helse: oppvekst og levekår. I Grøholt, Else Karin; Bøhler, Linn & Hånes, Hanna (Red.), Folkehelserapporten - Helsetilstanden i Norge. Folkehelseinstituttet. Fulltekst i vitenarkiv
• Bakke, Jan Vilhelm; Øvrevik, Johan; Schwarze, Per Everhard; Hongslo, Jan Kenneth; Nilsen, Steinar Klubben & Becher, Rune (2018). Textila golv, inomhusmiljö och hälsoeffekter. Astma og allergiforbundet. Fulltekst i vitenarkiv
• Bakke, Jan Vilhelm; Becher, Rune; Nilsen, Steinar Klubben & Øvrevik, Johan (2016). Teppegulv, inneklima og helse. Arkitektur N. ISSN 1504-7628. Fulltekst i vitenarkiv
• Bakke, Jan Vilhelm; Øvrevik, Johan; Schwarze, Per E.; Hongslo, Jan K.; Nilsen, Steinar Klubben & Becher, Rune (2016). Teppegulv, inneklima og helsepåvirkning. Fagbladet Allergi i praksis. ISSN 0806-5462. Fulltekst i vitenarkiv
• Nilsen, Steinar Klubben; Bakke, Jan Vilhelm; Becher, Rune & Øvrevik, Johan (2016). Teppegulv, inneklima og helse. Renholdsnytt. ISSN 1504-9205. Fulltekst i vitenarkiv
• Bakke, Jan Vilhelm; Becher, Rune; Bøhlerengen, Trond; Haugen, Elisabeth; Wergeland, Ebba & Øvrevik, Johan (2015). Bygninger må holdes rene og tørre. Fuktskader er tekniske og bygningsfysiske problemer som skal forebygges og utbedres raskt. Yrkeshygienikeren. ISSN 0802-2763. s. 10–11. Fulltekst i vitenarkiv
• Øvrevik, Johan (2014). Formation of reactive oxygen species in granulocytes is not inflammation. Indoor Air. ISSN 0905-6947. 24(6), s. 662–663. doi: 10.1111/ina.12105. Fulltekst i vitenarkiv
• Knudsen, Ann Kristin Skrindo; Forthun, Ingeborg; Madsen, Christian; Dahl, Jesper; Lyngstad, Trude Marie & Tvedten, Hilde Marie [Vis alle 15 forfattere av denne artikkelen] (2024). Dødelighet i Norge under koronapandemien 2020-2023. Folkehelseinstituttet. ISSN 9788284064512. Fulltekst i vitenarkiv Vis sammendrag

  Overvåking av dødelighet og beregninger av overdødelighet er viktig for å forstå hvordan dødeligheten i den norske befolkningen har vært i pandemiperioden. I denne rapporten viser vi beregninger av overdødelighet basert på data per uke eller kvartal i perioden 2020 til 2023. Vi beregner overdødelighet ved å sammenlikne observert dødelighet med forventet dødelighet. Beregningen av forventet dødelighet forutsetter at utviklingen i dødelighet følger trendene fra de siste ti årene før pandemien, justert for endringer i befolkningens størrelse og alderssammensetning. Denne rapporten oppdaterer beregningene fra rapporten «Dødelighet i Norge under koronapandemien 2020-2022». Det er gjort noen oppdateringer i modelleringen av forventet dødelighet fra fjorårets rapport. Vi beregner at det var en overdødelighet på 5,6 prosent i 2023 (uke 1 til og med uke 52). Dette tilsvarer 2 313 flere dødsfall enn forventet. De fleste av disse ekstra dødsfallene var i aldersgruppen 65 år og eldre. Overdødeligheten i denne perioden er omtrent halvert sammenliknet med tilsvarende periode i 2022, da våre oppdaterte analyser anslår en overdødelighet på 11,8 prosent. Resultatene indikerer overdødelighet blant menn, men ikke blant kvinner. Beregninger basert på data per kvartal indikerer forhøyet dødelighet for alle aldersgrupper unntatt de aller eldste, med statistisk signifikant overdødelighet for aldersgruppene 20-39 år, 65-79 år og 80- 89 år. Det er stor usikkerhet rundt beregningene fordi det nå har gått lang tid siden referanseperioden (2010-2019). Usikkerheten er særlig stor i de yngre aldersgruppene fordi det i tillegg er få dødsfall i disse gruppene, og årlige antall derfor er mer utsatt for tilfeldige svingninger fra år til år. Vi har i tillegg sett på foreløpige tall for de store dødsårsaksgruppene i 2023. Endelig og utfyllende informasjon om dødsårsaker i 2023 kommer 30. mai 2024 når dødsårsaksstatistikken publiseres. Covid-19-assosierte dødsfall er fortsatt en viktig årsak til overdødeligheten. Det ble registrert 1 546 covid-19-assosierte dødsfall i 2023, og ni av ti av disse fant sted i befolkningen over 70 år. Foreløpige tall indikerer ingen vesentlig økning i 2023 for dødsfall som skyldes hjerte- og karsykdom, demens og kreft sammenliknet med foregående år. Det er fortsatt knyttet stor usikkerhet til hvordan dødeligheten i Norge vil utvikle seg fremover. Norske data må sees i sammenheng med nordiske og internasjonale data for å få mer kunnskap om hva som er spesielt for Norge, og hva som er globale utviklingstrekk. Folkehelseinstituttet vil fortsette sin forskning på og overvåkning av dødelighet og dødsårsaker.

• Bølling, Anette Kocbach; Aasvang, Gunn Marit; Låg, Marit; Refsnes, Magne Arnold; Øvrevik, Johan & Oftedal, Bente Margaret (2021). Konsentrasjons-responskurver for svevestøv: PM10. Folkehelseinstituttet. ISSN 9788284062372. Fulltekst i vitenarkiv Vis sammendrag

  Hovedbudskap: Luftforurensning er blant de miljøfaktorene som bidrar mest til sykdom og død, både i Norge og i resten av verden. Luftforurensning består av både svevestøv og gasser som kan bidra til uønskede helsevirkninger, avhengig av hvilke konsentrasjoner de finnes i. Sammenhengen mellom eksponering for svevestøv og forskjellige helsevirkninger, som for eksempel økt risiko for tidlig død, er godt dokumentert. Gjennomføring av politiske tiltak baseres ofte på kvantitative helserisikovurderinger eller kost-nyttevurderinger. Disse involverer bruk av konsentrasjons-responskurver som beskriver sammenhengen mellom eksponering for en luftforurensningskomponent og en spesifikk helsevirkning. Konsentrasjons-responskurver for svevestøv baseres på data fra befolkningsstudier. Formen til konsentrasjons-responskurven kan ha stor betydning for resultatet av de kvantitative vurderingene som danner grunnlag for politiske tiltak. Tilsvarende, kan bruk av terskelverdi i kurvene, altså en nedre grense for hvilke svevestøvkonsentrasjoner som fører til økt risiko for dødelighet, også ha stor betydning. Ofte brukes terskelverdier for å gjenspeile usikkerheten i sammenhengen mellom helserisiko og eksponering for de aller laveste konsentrasjonene. Usikkerheten skyldes at befolkningsstudiene har lite data for slike lave konsentrasjoner. Denne typen terskelverdi kalles teoretisk terskelverdi i denne rapporten. Det er viktig å merke seg at konsentrasjons-responskurvene, og bruken av disse i kvantitative vurderinger, er i stadig utvikling grunnet den kontinuerlige oppdateringen av kunnskapsgrunnlaget. Svevestøv («particulate matter»; PM) deles ofte inn etter størrelsen i fint og grovt svevestøv. Fint svevestøv refererer til partikler som er mindre enn 2,5 µm (PM2,5), mens grovt svevestøv er partikler mellom 2,5 og 10 µm (PM10-2,5). PM10 er summen av fint og grovt svevestøv, altså partikler som er mindre enn 10 µm. Eksponeringen for PM10 i befolkningen beskrives vanligvis i form av gjennomsnittlig eksponering i løpet av et år (årsmidlet) eller i løpet av et døgn (døgnmidlet). I denne rapporten oppsummeres kunnskapsgrunnlaget for konsentrasjons-responskurver for årsmidlet og døgnmidlet eksponering for PM10 og risiko for tidlig død, med fokus på kurveform og terskelverdi. I tillegg gis konkrete anbefalinger for kurver for bruk i kvantitative helserisikovurderinger. Den foreliggende rapporten om konsentrasjons-responskurver for PM10, bygger i stor grad på rapporten om kurver for PM2,5 fra 2018. Lesere henvises til rapporten fra 2018 for en grundigere introduksjon til de underliggende faglige metodene og mulige bruksområder for konsentrasjons-responskurver. For begge eksponeringsmålene anbefales bruk av en teoretisk terskelverdi som gjenspeiler usikkerheten i sammenhengen mellom eksponering og dødelighet for de laveste konsentrasjonene. Den anbefalte kurven for årsmidlet PM10 er basert på studier fra hele verden, men data fra Norge var ikke inkludert i analysen. Det er imidlertid ønskelig med kurver basert på data fra norske eller nordiske befolkningsstudier, siden dette vil bidra til en mer nøyaktig kvantifisering av helserisiko i den norske befolkningen. For fremtidige kvantitative helserisikovurderinger bør det også vurderes om størrelsesfraksjonene PM10-2,5 og PM2,5 bør vurderes separat, og så summeres. Den anbefalte kurven for døgnmidlet PM10 er basert på en multisenterstudie fra Europa, som ikke inkluderte norske data. Selv om det er viktig med økt kunnskap om for tidlig død knyttet til døgnmidlet eksponering for PM10 i Norge, er det først og fremst behov for videreutvikling av metodikken for kvantitative helserisikovurderinger for døgnmidlet eksponering. For fremtidige kvantitative helserisikovurderinger er det ønskelig å inkludere ulike mål på sykelighet for både årsmidlet og døgnmidlet PM10. Dette vil gi en mer korrekt vurdering av konsekvenser av PM10 eksponering for helse, men det er da behov for en ny kunnskapsgjennomgang for å anbefale hvilke mål på sykelighet og konsentrasjons-responskurver som bør inkluderes.

• Bølling, Anette Kocbach; Aasvang, Gunn Marit; Oftedal, Bente Margaret; Låg, Marit; Refsnes, Magne Arnold & Øvrevik, Johan [Vis alle 7 forfattere av denne artikkelen] (2018). Kunnskapsoppsummering. Konsentrasjons-responskurver for lave konsentrasjoner av svevestøv. Folkehelseinstituttet. ISSN 9788280829399. Fulltekst i vitenarkiv
• Låg, Marit; Refsnes, Magne Arnold & Øvrevik, Johan (2017). Vurdering av mulig helserisiko forbundet med høye svevestøvnivåer ved Nationaltheateret stasjon - Oslo. Folkehelseinstituttet. ISSN 9788280828927. Fulltekst i vitenarkiv
• Krog, Norun Hjertager; Refsnes, Magne Arnold; Aasvang, Gunn Marit; Låg, Marit & Øvrevik, Johan (2017). Flystøy og luftforurensning ved flyplasser: Mulige helsekonsekvenser ved Oslo lufthavn. Folkehelseinstituttet. ISSN 9788280828743. Fulltekst i vitenarkiv Vis sammendrag

  Denne rapporten er skrevet på oppdrag fra Ullensaker kommune. Som vertskap for Norges hovedflyplass Oslo lufthavn (OSL) ønsket kommunen oppdatert vitenskapelig kunnskap om mulige virkninger på befolkningens helse og trivsel av de støynivåene man har i nærområdet til flyplassen. Kommunen ønsket også en vurdering av mulig luftforurensning ved flyplassen, og hva som kan være helsemessige konsekvenser av denne. Folkehelseinstituttet (FHI) oppsummerer i denne rapporten kunnskapsstatus når det gjelder flystøy, luftforurensning rundt flyplasser og helse. Ulike studier har funnet sammenhenger mellom støyeksponering, luftforurensning og en rekke ulike helseutfall. I denne rapporten har vi valgt å avgrense oss til de best dokumenterte/hyppigst studerte virkningene av flystøy, som er støyplage, søvnforstyrrelser og hjerte- og karsykdom, samt virkninger av flystøy på barn og deres læring. I rapporten går vi også inn på kunnskapen om luftforurensning fra flytrafikken og tilknyttede aktiviteter på flyplassen. På grunnlag av beregninger av flystøy og luftforurensning i områdene rundt OSL gjøres en risikovurdering av hvilke helseeffekter som kan forventes for befolkningen i nærområdene. I litteraturgjennomgangen har vi også identifisert kunnskapshull, og gir anbefalinger for videre forskning. Marita Heintz, spesialbibliotekar ved FHIs bibliotek, har stått for de systematiske litteratursøkene. Rapporten har vært gjennom en høringsprosess der vi har innhentet innspill fra SINTEF og Ullensaker kommune, i tillegg til relevante fagpersoner internt ved FHI. Vi retter en stor takk til alle som har bidratt på denne måten. Rapporten representerer FHIs vurderinger, og ansvaret for sluttproduktet er forfatternes alene.

• Becher, Rune; Øvrevik, Johan; Høie, Anja Hortemo; Bakke, Jan Vilhelm & Holøs, Sverre Bjørn (2016). Fukt og fuktskader i norske boliger. Folkehelseinstituttet. ISSN 9788280827777. Fulltekst i vitenarkiv Vis sammendrag

  Forord. Flere store studier har vist at fuktproblemer og muggsopp i inneklimasammenheng er risikofaktorer for luftveisrelaterte sykdomsutfall. Dette er viktig for både det forebyggende arbeidet og på tiltakssiden når det gjelder inneklima og helse. Vi vet imidlertid lite om bygningsmessige forhold eller eksponeringssituasjoner av betydning for inneklimaet i Norge. Dette gjelder også forekomsten vi har av fuktproblemer i den norske bygningsmassen og om det har vært en reell økning i forekomsten av fuktproblemer. Både fra et helsemessig og et bygningsteknisk ståsted er det derfor viktig at man får økt kunnskap om omfanget av fuktrelaterte inneklimaproblemer i Norge. Folkehelseinstituttet ved Område for smittevern, miljø og helse, avdeling Luft og støy, fikk i 2015 i oppdrag fra Helsedirektoratet å kartlegge omfanget av fuktproblemer i den norske boligmassen. For å løse det tildelte oppdraget har Folkehelseinstituttet benyttet tilgjengelige data fra firmaet Anticimex. Anticimex har over tid samlet et stort datamateriale fra tilstandsundersøkelser av boliger over hele Norge i forbindelse med gjennomføring av «If Boligsjekk» på oppdrag for If Skadeforsikring. If Skadeforsikring har, som formell eier, stilt datamaterialet fra «If Boligsjekk» til disposisjon for denne undersøkelsen.

• Becher, Rune; Bjerke, Marianne; Martinsen, Finn & Øvrevik, Johan (2016). Inneklima i skoler og barnehager: Helsemessig betydning for barn og unge. Folkehelseinstituttet. ISSN 9788280827784. Fulltekst i vitenarkiv Vis sammendrag

  Barn og unge er følsomme grupper med hensyn til eksponering for luftforurensninger. Dette skyldes i stor grad aldersbetingede forskjeller i fysiologi og toksikokinetikk (opptak, fordeling, omdanning og utskillelse) samt eventuelle eksisterende sykdommer og arvelige faktorer. Barn, spesielt de minste, puster også inn mer luft i forhold til kroppsvekt, har større grad av hånd-til-munnkontakt, og er generelt dårligere til å unngå eksponeringssituasjoner. Dette er faktorer som øker den relative eksponeringen for luft og støvbårne forurensninger. Godt inneklima i skoler og barnehager har stor betydning for helse, trivsel og læring for barn og unge. Både befolkningsstudier og toksikologisk/biologisk forskning har vist at flere risikoforhold i inneklimasammenheng kan knyttes til uønskede helseeffekter. Eksempler på slike risikoforhold er fuktproblemer og muggvekst, en del kilder til flyktige organiske forbindelser, høy partikkelforurensning, radon og allergener. De uønskede helseeffektene synes særlig å være knyttet til luftveissykdommer (infeksjoner, astma og luftveisallergi), irritasjon av slimhinner og hodepine. Det gjør det viktig å forebygge og utbedre de risikoforhold som har sterkest sammenheng med helserisiko i inneklimasammenheng. Flere studier har videre vist at uheldige inneklimaforhold knyttet til ventilasjon, temperatur og belysning i skoler og barnehager kan påvirke skoleprestasjoner og arbeidsevne. Selv om vi med dagens kunnskap ikke kan angi eksakte tall for hvor mange som kan bli eller er syke som følge av dårlig inneklima, vet vi nok til å ta barn, unge og inneklima i skoler og barnehager alvorlig. Ut fra de utvalgsundersøkelser som er gjort fremgår det at svært mange skoler i Norge har et dårlig inneklima på grunn av manglende vedlikehold. Eksempelvis er det gjennom Arbeidstilsynets arbeid avdekket at ca halvparten av 301 skoler hadde eller hadde hatt problemer med vannlekkasjer og/eller fuktproblematikk. Utdannings- og helsemyndighetenes kartlegginger av landets skoler i senere tid viser at ca. 900 skoler mangler godkjenning etter regelverket om miljørettet helsevern i barnehager og skoler. Vi mener det er god grunn til å anta at antall barn som opplever uønskede helseutfall, plager og nedsatt trivsel på grunn av dårlig inneklima er relativt høyt. Det er også grunn til å anta at dårlige inneklimaforhold i skoler kan gå ut over barnas skoleprestasjoner. Svært ofte synes inneklimaproblemene i skoler og barnehager å være knyttet til sviktende forvaltning, drift og vedlikehold. Med det vi vet i dag, vil sannsynligvis de fleste inneklimaproblemer kunne reduseres eller unngås helt forutsatt at både samfunnet og enkeltpersoner er villig til å bruke tid og ressurser på dette.

• Låg, Marit; Refsnes, Magne Arnold; Schwarze, Per Everhard; Landvik, Nina; Maass, Christine & Øvrevik, Johan [Vis alle 10 forfattere av denne artikkelen] (2013). Luftkvalitetskriterier : virkninger av luftforurensning på helse. Folkehelseinstituttet. ISSN 9788280825889. Fulltekst i vitenarkiv
• Thormodsæter, Anders; Låg, Marit; Øvrevik, Johan; Holme, Jørn Andreas & Øvrebø, Steinar (2011). Sink- og arsen-indusert kjemokinfrigjøring og cytotoksisitet i humane bronkiale epitelceller. Universitetet i Oslo. Fulltekst i vitenarkiv Vis sammendrag

  Svevestøv eller partikulært materiale (PM) er assosiert med helseskader og utvikling og forverring av lungesykdommer som kronisk obstruktiv lungesykdom (KOLS), astma og lungekreft. I dette studiet har vi undersøkt eksponering for sink og arsen i en human epitelial cellelinje. Disse metallene har blitt vist å indusere helseskader hos mennesker både i form av komponenter i PM, og som metaller alene. Bronkiale epitelceller, BEAS-2B, ble eksponert for sink (Zn2+), arsenitt og arsenat. Cytotoksisitets-data etter farging med propidium iodid (PI) og Hoechst 33342 og analyse ved hjelp av fluorescensmikroskopi, viste at arsenitt induserte nekrose og apoptose ved lavere konsentrasjoner enn sink og arsenat. Videre induserte eksponering for arsenitt en opphopning av celler i mitose analysert ved fluorescensmikroskopi og flowcytometri. Dette indikerer en rolle for arsenitt i mitotisk arrest. Eksponering for arsenat ga også opphopning av celler i mitose, men ved høyere konsentrasjoner enn arsenitt. Sink, arsenitt og arsenat induserte en økning i CXCL8-frigjøring ved lavere konsentrasjoner enn induksjon av celledød. Både sink og arsenitt så ut til å aktivere mitogen-aktiverte protein kinaser (MAPK) fordi nivåene av fosforylerte ekstracellulær signal-regulert kinase (ERK) og p38 økte ved eksponering for metallene. Videre ga hemming av p38 en reduksjon av den metallinduserte CXCL8-frigjøringen til basale nivåer, mens hemming av ERK ga bare en delvis reduksjon. Dette indikerer en viktig rolle for MAPK i produksjon av CXCL8. Transkripsjonsfaktoren nukleær faktor kappa B (NF-κB) ble aktivert av begge metaller. Både sink og arsenitt induserte oksidativt stress målt ved økte nivåer av H2O2 (DCFD-HA), og O2 - (DHE), samt induksjon av heme oxygenase-1 (HO-1). Dette ble målt ved tilsvarende konsentrasjoner som ga maksimal CXCL8-frigjøring. Forbehandling med antioksidanten N-acetyl-L-cystein (NAC) reduserte CXCL8-frigjøringen indusert av sink og arsenitt. Dessuten ble også opphopningen av celler i mitose observert for arsenitt redusert. Difenylen iodonium (DPI), en NAD(P)H oxidase inhibitor, reduserte ikke CXCL8-frigjøringen, men reduserte opphopning av celler i mitose. En mulig additiv effekt ble observert ved kombinert eksponering av sink og arsenitt på CXCL8-frigjøring og cytotoksisitet. Kort oppsummert induserte eksponering for både sink og arsenitt inflammatoriske responser inkludert oksidativt stress, cytotoksisitet og CXCL8-frigjøring i bronkiale epiteliale lungeceller. Dette indikerer en mulig rolle for metallene i negative helseeffekter indusert av PM. Dannelse av frie oksidative radikaler, aktivering av MAPK og NF-κB er trolig involvert i inflammasjonsresponsene.

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