六价铬[Cr(VI)]是一种被国际癌症研究机构（IARC）分类为I类致癌物的物质，是最普遍的职业和环境污染物之一。人类流行病学和实验动物研究发现，长期接触Cr(VI)会导致肺癌和其他癌症。虽然Cr(VI)是公认的 致癌物，但其致癌机制还不完全清楚。由于Cr(VI)进入细胞后会经历一系列代谢还原反应，产生活性Cr代谢产物和活性氧自由基（ROS），导致基因毒性，所以普遍认为Cr(VI)是一种基因毒性致癌物。然而，越来越多的研究表明，急性或慢性接触Cr(VI)还会导致表观遗传学失调，包括改变DNA甲基化、组蛋白翻译后修饰和调节非编码RNA（微小RNA和长非编码RNA）表达。此外，新兴证据表明，Cr(VI)暴露还能够改变细胞表观转录组。鉴于表观遗传学和表观转录组失调在癌症起始和进展中的重要性越来越受到认可，人们认为Cr(VI)暴露引起的表观遗传和表观转录组变化可能在Cr(VI)致癌中发挥重要作用。本章的目的是回顾Cr(VI)暴露对表观遗传和表观转录组的影响，并讨论其在Cr(VI)致癌中的作用。更好地了解Cr(VI)致癌机制可能有助于鉴定新的分子靶标，实现更高效的预防和治疗因Cr(VI)暴露导致的癌症。版权所有©2023 Elsevier Inc.

Hexavalent chromium [Cr(VI)], a Group I carcinogen classified by the International Agency for Research on Cancer (IARC), represents one of the most common occupational and environmental pollutants. The findings from human epidemiological and laboratory animal studies show that long-term exposure to Cr(VI) causes lung cancer and other cancer. Although Cr(VI) is a well-recognized carcinogen, the mechanism of Cr(VI) carcinogenesis has not been well understood. Due to the fact that Cr(VI) undergoes a series of metabolic reductions once entering cells to generate reactive Cr metabolites and reactive oxygen species (ROS) causing genotoxicity, Cr(VI) is generally considered as a genotoxic carcinogen. However, more and more studies have demonstrated that acute or chronic Cr(VI) exposure also causes epigenetic dysregulations including changing DNA methylation, histone posttranslational modifications and regulatory non-coding RNA (microRNA and long non-coding RNA) expressions. Moreover, emerging evidence shows that Cr(VI) exposure is also capable of altering cellular epitranscriptome. Given the increasingly recognized importance of epigenetic and epitranscriptomic dysregulations in cancer initiation and progression, it is believed that Cr(VI) exposure-caused epigenetic and epitranscriptomic changes could play important roles in Cr(VI) carcinogenesis. The goal of this chapter is to review the epigenetic and epitranscriptomic effects of Cr(VI) exposure and discuss their roles in Cr(VI) carcinogenesis. Better understanding the mechanism of Cr(VI) carcinogenesis may identify new molecular targets for more efficient prevention and treatment of cancer resulting from Cr(VI) exposure.Copyright © 2023 Elsevier Inc. All rights reserved.