研究动态
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由基因毒性职业和环境化学致癌物质引起的表观遗传修饰:一篇系统文献综述的最新更新。

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: An update of a systematic literature review.

发表日期:2022
作者: Samantha Goodman, Grace Chappell, Kathryn Z Guyton, Igor P Pogribny, Ivan Rusyn
来源: Mutat Res-Rev Mutat

摘要:

表观遗传变化,如DNA甲基化、组蛋白/染色质结构的改变、核小体定位以及非编码RNA的表达变化,被认为是致癌物的关键特征之一;它们可能独立发生或与基因毒性效应同时发生。虽然关于基因毒性的数据是通过标准化指南测试收集的,但收集到的有关表观遗传效应的数据则远没有那么统一。2016年,我们对已发表的有关基因毒性致癌物的表观遗传终点报道的研究进行了系统回顾,以更好地了解人类致癌物的表观遗传变化证据及其与基因毒性终点的潜在关联。自那以后,化学物质影响的表观遗传作用的研究数量几乎翻了一倍。本回顾对先前和最近被国际癌症研究机构分类为一类的职业和环境致癌物诱导的表观遗传变化进行了更新。我们发现,各种表观遗传效应的证据仍然不均匀。DNA甲基化的研究最为丰富,而有关非编码RNA的影响的报道则在过去5年中增加了。相比之下,有关组蛋白修饰和染色质状态变化的机理毒理学研究仍然很少。我们发现,大多数有关致癌物表观遗传效应的出版物都是对暴露于人类或人类细胞的研究。鼠类的研究是毒理学表观遗传研究中使用第二普遍的物种,体内暴露是最主要的。未来的研究应该采用剂量和时间依赖的研究设计,并考虑着重于大多数表观遗传变化的动态性的曝露停止后效应的持续性。版权所有©2021 Elsevier B.V.。
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.Copyright © 2021 Elsevier B.V. All rights reserved.