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A molecular epidemiology study of workers exposed to diesel engine exhaust
Citation:
Lan, Q., R. Vermeulen, Y. Dai, W. Hu, B. Bassig, E. Drizik, S. Corbett, D. Ren, H. Duan, Y. Niu, W. Fu, K. Meliefste, B. Zhou, W. Martin, S. Warren, H. Liberatore, M. Ye, X. Jia, T. Meng, P. Bin, J. Wong, H. Hosgood III, A. Spira, D. DeMarini, M. Lenburg, D. Silverman, Y. Zheng, AND N. Rothman. A molecular epidemiology study of workers exposed to diesel engine exhaust. Presented at 28th International Symposium on Epidemiology in Occupational Health, EPICOH 2020, Montreal, Quebec, CANADA, August 31 - September 03, 2020.
Impact/Purpose:
Diesel Exhaust was evaluated as a Group 1 (known) human lung carcinogen by IARC in 2014. However, there has been weak but persistent epidemiology suggesting that diesel exhaust is also a human bladder carcinogen. There has been mechanistic support for this based on the fact that human metabolize the nitroarenes in diesel exhaust to aromatic amines, which are bladder carcinogens. To address this issue further, this study explored a wide set of molecular biomarkers in a study in China where a number of subjects worked for various numbers of years in a diesel bus-repair facility, and others had little to now exposure to diesel exhaust. The data provide supporting mechanistic evidence that diesel exhaust may be a human bladder carcinogen. This might prompt IARC to evaluate diesel exhaust for carcinogenicity of the bladder, and this could impact how various agencies and nations regulate diesel exhaust.
Description:
Objective: Diesel engine exhaust (DEE) is a known lung carcinogen and may be associated with other tumors including bladder cancer. However, the underlying mechanisms by which DEE causes cancer in humans is not well understood. Our goal was to conduct a comprehensive cross-sectional molecular epidemiology study of workers exposed to DEE to evaluate both tissue-specific and systemic biologic effects. Methods: We identified a diesel truck engine testing facility with a wide range of DEE levels and control factories without occupational DEE exposure. We conducted an extensive exposure assessment over several years, with frequent personal air sample measurements during the months leading up to the clinical phase of the study. We collected nasal turbinate samples stabilized for RNA, oral and sputum samples, urine samples for mutagenicity testing and collection of exfoliated urothelial cells, and peripheral blood samples that were analyzed within 24 h of collection for the major lymphocyte subsets. Results: We enrolled 54 workers exposed to a wide range of DEE (elemental carbon (EC) air levels (median, range: 49.7, 6.1–107.7 μg/m3) and 55 comparable controls. We identified a DEE gene-expression signature in nasal turbinate samples, which are considered good surrogates for gene expression in the lung, comprised of 225 genes enriched in pathways related to oxidative stress response, cell-cycle pathways, protein modification, and transmembrane transport. EC exposure was also associated with an increase in urine mutagenicity, higher circulating CD4+ T cells, and alterations in plasma levels of two inflammatory biomarkers (CRP and CCL15/MIP-1D) and two microRNAs (miR-191-5p and miR-93-5p). Conclusion: DEE was associated with alterations in multiple biologic endpoints and pathways that play an important role in carcinogenesis. Ongoing analyses, including metabolomics, DNA methylation, and microbiomics, should continue to add to our understanding of the mechanisms through which DEE causes cancer. [Abstract does not necessarily reflect the policies of the U.S. EPA.]