OBJECTIVES: This study aimed to assess the biological impact of occupational exposure to diesel exhaust (DE) including DE particles (DEP) from heavy-duty diesel-powered equipment in Norwegian tunnel finishing workers (TFW). METHODS: TFW (n=69) and referents (n=69) were investigated for bulky DNA adducts (by 32P-postlabelling) and expression of microRNAs (miRNAs) (by small RNA sequencing) in peripheral blood mononuclear cells (PBMC), as well as circulating free arachidonic acid (AA) and eicosanoid profiles in plasma (by liquid chromatography-tandem mass spectrometry). RESULTS: PBMC from TFW showed significantly higher levels of DNA adducts compared with referents. Levels of DNA adducts were also related to smoking habits. Seventeen miRNAs were significantly deregulated in TFW. Several of these miRNAs are related to carcinogenesis, apoptosis and antioxidant effects. Analysis of putative miRNA-gene targets revealed deregulation of pathways associated with cancer, alterations in lipid molecules, steroid biosynthesis and cell cycle. Plasma profiles showed higher levels of free AA and 15-hydroxyeicosatetraenoic acid, and lower levels of prostaglandin D2 and 9-hydroxyoctadecadienoic acid in TFW compared with referents. CONCLUSION: Occupational exposure to DE/DEP is associated with biological alterations in TFW potentially affecting lung homoeostasis, carcinogenesis, inflammation status and the cardiovascular system. Of particular importance is the finding that tunnel finishing work is associated with an increased level of DNA adducts formation in PBMC.

Department of Analytical Environmental and Forensic Sciences MRC PHE Centre for Environment and Health King's College London London UK

Department of Chemistry and Toxicology Veterinary Research Institute Brno Czech Republic

Department of Computer Science Czech Technical University Prague Prague Czech Republic

Department of Genetic Toxicology and Nanotoxicology Institute of Experimental Medicine of the Czech Academy of Sciences Prague Czech Republic

Department of Occupational Medicine and Epidemiology National Institute of Occupational Health Oslo Norway

Department of Work Psychology and Physiology National Institute of Occupational Health Oslo Norway

NIHR Health Protection Research Unit in Health Impact of Environmental Hazards at King's College London in Partnership with Public Health England and Imperial College London London UK

Section for Toxicology and Biological Work Environment Department of Chemical and Biological Work Environment National Institute of Occupational Health Oslo Norway

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