Epigenetic Alterations Induced By Genotoxic Occupational And Environmental Human Chemical Carcinogens: A Systematic Literature Review

RUSYN I. ¹

Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although changes to the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To gain a better understanding of the body of evidence of epigenetic alterations, and their potential association with genotoxic endpoints, we conducted a systematic review of published studies that reported epigenetic alterations associated with exposure to genotoxic environmental and/or occupational hazards. Specifically, we searched for reports of epigenetic alterations in studies of one or more of the 31 agents and occupations that are listed in the International Agency for the Research on Cancer (IARC) monographs volume 100F, one component of an extensive re-evaluation of data on known human carcinogens. Of the 31 agents and occupations, 28 have strong evidence of a genotoxic mechanism of carcinogenesis, and we narrowed our literature review to those. We identified a total of 156 studies that evaluated one or more epigenetic alterations in 12 of the 28 included agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation represented the most commonly studied epigenetic feature, followed by changes in the expression of non-coding RNAs, and finally histone modifications (totaling 85, 59, and 25 studies, respectively). For 3 carcinogens (benzo[a]pyrene, aflatoxins and benzene), 10 or more studies reporting epigenetic endpoints were identified. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in current cancer hazard assessments.