Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, United States.
Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY, United States; Center for Research on Environment Disease, College of Medicine, University of Kentucky, Lexington, KY, United States.
Semin Cancer Biol. 2019 Aug;57:95-104. doi: 10.1016/j.semcancer.2019.01.002. Epub 2019 Jan 11.
Arsenic, cadmium, nickel and hexavalent chromium are among the most common environmental pollutants and potent carcinogens. Chronic exposure to these metals causes various types of cancer in humans, representing a significant environmental health issue. Although under active investigation, the mechanisms of metal carcinogenesis have not been clearly defined. One common feature of these metal carcinogens is that they are all able to cause various epigenetic dysregulations, which are believed to play important roles in their carcinogenicity. However, how metal carcinogen-caused epigenetic dysregulation contributes to metal carcinogenesis remains largely unknown. The evolution of cancer stem cell (CSC) theory has opened exciting new avenues for studying the mechanism of metal carcinogenesis. Increasing evidence indicates that chronic metal carcinogen exposure produces CSC-like cells through dysregulated epigenetic mechanisms. This review will first provide some brief introductions about CSC, epigenetics and epigenetic regulation of CSCs; then summarize progresses in recent studies on metal carcinogen-induced CSC-like property through epigenetic reprograming as a novel mechanism of metal carcinogenesis. Some perspectives for future studies in this field are also presented.
砷、镉、镍和六价铬是最常见的环境污染物和强致癌物质之一。慢性暴露于这些金属会导致人类患上各种类型的癌症，这是一个重大的环境健康问题。尽管这些金属致癌物质的致癌机制仍在积极研究中，但尚未明确界定。这些金属致癌物质的一个共同特点是，它们都能够引起各种表观遗传失调，而这些失调被认为在它们的致癌性中起着重要作用。然而，金属致癌物质引起的表观遗传失调如何导致金属致癌仍知之甚少。癌症干细胞（CSC）理论的发展为研究金属致癌机制开辟了令人兴奋的新途径。越来越多的证据表明，慢性金属致癌剂暴露通过失调的表观遗传机制产生 CSC 样细胞。本文首先简要介绍 CSC、表观遗传学和 CSCs 的表观遗传调控；然后总结近年来关于金属致癌剂通过表观遗传重编程诱导 CSC 样特性的研究进展，作为金属致癌作用的一种新机制。还提出了该领域未来研究的一些观点。
