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Original article
Bulky DNA adducts, microRNA profiles, and lipid biomarkers in Norwegian tunnel finishing workers occupationally exposed to diesel exhaust
  1. Iselin Rynning1,
  2. Volker M Arlt2,3,
  3. Kristyna Vrbova4,
  4. Jiří Neča5,
  5. Pavel Rossner Jr4,
  6. Jiri Klema6,
  7. Bente Ulvestad7,
  8. Elisabeth Petersen8,
  9. Øivind Skare7,
  10. Aage Haugen1,
  11. David H Phillips2,3,
  12. Miroslav Machala5,
  13. Jan Topinka4,
  14. Steen Mollerup1
  1. 1Section for Toxicology and Biological Work Environment, Department of Chemical and Biological Work Environment, National Institute of Occupational Health, Oslo, Norway
  2. 2Department of Analytical, Environmental and Forensic Sciences, MRC-PHE Centre for Environment and Health, King’s College London, London, UK
  3. 3NIHR 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
  4. 4Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic
  5. 5Department of Chemistry and Toxicology, Veterinary Research Institute, Brno, Czech Republic
  6. 6Department of Computer Science, Czech Technical University in Prague, Prague, Czech Republic
  7. 7Department of Occupational Medicine and Epidemiology, National Institute of Occupational Health, Oslo, Norway
  8. 8Department of Work Psychology and Physiology, National Institute of Occupational Health, Oslo, Norway
  1. Correspondence to Dr Steen Mollerup, Section for Toxicology and Biological Work Environment, Department of Chemical and Biological Work Environment, National Institute of Occupational Health, Oslo 0304, Norway; steen.mollerup{at}stami.no

Abstract

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.

  • diesel fumes
  • toxicology
  • biomonitoring
  • polyaromatic hydrocarbons (pahs)
  • particulates

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Footnotes

  • Contributors Study design was led by IR and SM, with contributions from BU, PR, VMA, DHP, MM, JT and AH. IR, EP and BU carried out enrolment of participants and collection of human samples. Data collection was carried out by IR, VMA, KV, JN and PR. IR, ØS and JK conducted statistical analyses. IR drafted the manuscript. All authors participated in data analysis, critically revised the manuscript and approved the final version.

  • Funding This work was financially supported by the Statoil Working Environment Fund (Norway) and the Ministry of Youth, Education and Sports of the Czech Republic (LO1508 to PR, JK and KV, LM2015073; CZ.02.1.01/0.0/0.0/16_013/0001821 to JT; the grant Research Center for Informatics CZ.02.1.01/0.0/0.0/16_019/0000765 to JK; project "FIT", no. CZ.02.1.01/0.0/0.0/15_003/0000495 to MM and JN). Work at King’s College London was supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Health Impact of Environmental Hazards at King’s College London in partnership with Public Health England and Imperial College London.

  • Disclaimer The views expressed in this article are those of the authors and not necessarily those of the UK National Health Service, the UK National Institute for Health Research Health, the UK Department of Health and Social Care or Public Heath England.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval The study was approved by the Norwegian Regional Committees for Medical and Health Research Ethics (REC #2014/2199).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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