Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although 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 better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic 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 was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. 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 cancer hazard assessments.

中文翻译：

---

遗传毒性职业和环境人类化学致癌物诱导的表观遗传学改变：系统文献综述。

越来越多的证据表明，表观遗传学改变在化学诱导的致癌作用中起着重要的作用。尽管表观基因组和基因组在致癌性中可能同等重要，但是化学试剂的遗传毒性和与暴露相关的转录组反应已经得到了更彻底的研究和表征。为了更好地了解人类致癌物表观遗传学改变的证据以及与遗传毒性终点的潜在关联，我们对发表了表观遗传终点的遗传毒性致癌物的已发表研究进行了系统综述。具体来说，我们搜索了国际癌症研究机构（IARC）专着100F所报告的28种病原体和职业的表观遗传学作用的出版物，这些出版物被归类为“对人类致癌”。（第1组）具有强有力的致癌遗传毒性机制证据。我们总共鉴定了158项研究，评估了这28种致癌剂和职业中的12种（1,3-丁二烯，4-氨基联苯，黄曲霉毒素，苯，联苯胺，苯并[a] re，焦炭生产，甲醛，职业暴露）的表观遗传学变化。作为画家，硫芥末和氯乙烯）。最常见的研究是异常的DNA甲基化，然后是非编码RNA的表达改变和组蛋白变化（分别共进行85、59和25个研究）。对于3种致癌物（黄曲霉毒素，苯和苯并[a] re），有10项或更多研究报告了表观遗传效应。然而，对其余9种致癌物的表观遗传学研究很少。对于4个特工，仅确定了1个或2个已发布的报告。