Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA.
ToxStrategies, Inc., Asheville, NC, USA.
Mutat Res Rev Mutat Res. 2022 Jan-Jun;789:108408. doi: 10.1016/j.mrrev.2021.108408. Epub 2021 Dec 9.
Epigenetic alterations, such as changes in DNA methylation, histones/chromatin structure, nucleosome positioning, and expression of non-coding RNAs, are recognized among key characteristics of carcinogens; they may occur independently or concomitantly with genotoxic effects. While data on genotoxicity are collected through standardized guideline tests, data collected on epigenetic effects is far less uniform. In 2016, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints to better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints. Since then, the number of studies of epigenetic effects of chemicals has nearly doubled. This review stands as an update on epigenetic alterations induced by occupational and environmental human carcinogens that were previously and recently classified as Group 1 by the International Agency for Research on Cancer. We found that the evidence of epigenetic effects remains uneven across agents. Studies of DNA methylation are most abundant, while reports concerning effects on non-coding RNA have increased over the past 5 years. By contrast, mechanistic toxicology studies of histone modifications and chromatin state alterations remain few. We found that most publications of epigenetic effects of carcinogens were studies in exposed humans or human cells. Studies in rodents represent the second most common species used for epigenetic studies in toxicology, in vivo exposures being the most predominant. Future studies should incorporate dose- and time-dependent study designs and also investigate the persistence of effects following cessation of exposure, considering the dynamic nature of most epigenetic alterations.
表观遗传改变，如 DNA 甲基化、组蛋白/染色质结构、核小体定位和非编码 RNA 的表达，被认为是致癌物质的主要特征之一；它们可能独立或与遗传毒性效应同时发生。虽然遗传毒性数据是通过标准化指南测试收集的，但关于表观遗传效应的数据则不那么统一。2016 年，我们对已发表的报告表观遗传终点的遗传毒性致癌物质研究进行了系统综述，以更好地了解人类致癌物质的表观遗传改变的证据，以及与遗传毒性终点的潜在关联。自那时以来，关于化学物质表观遗传效应的研究数量几乎翻了一番。本综述是对先前和最近被国际癌症研究机构（IARC）归类为 1 组的职业和环境人类致癌物质所诱导的表观遗传改变的更新。我们发现，各物质的证据仍然不均匀。关于 DNA 甲基化的研究最为丰富，而在过去 5 年中，关于非编码 RNA 影响的报告有所增加。相比之下，组蛋白修饰和染色质状态改变的机制毒理学研究仍然很少。我们发现，大多数致癌物质表观遗传效应的出版物都是暴露于人类或人类细胞中的研究。在毒理学中，啮齿动物研究是第二常见的用于研究表观遗传的物种，体内暴露是最主要的。未来的研究应纳入剂量和时间依赖性研究设计，并在考虑到大多数表观遗传改变的动态性质的情况下，研究暴露停止后效应的持久性。
