Idoia Meaza, Aggie R Williams, Sandra S Wise, Haiyan Lu, John W Pierce
{"title":"Carcinogenic Mechanisms of Hexavalent Chromium: From DNA Breaks to Chromosome Instability and Neoplastic Transformation.","authors":"Idoia Meaza, Aggie R Williams, Sandra S Wise, Haiyan Lu, John W Pierce","doi":"10.1007/s40572-024-00460-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Hexavalent chromium [Cr(VI)] is a well-established human carcinogen, yet the mechanisms by which it leads to carcinogenic outcomes is still unclear. As a driving factor in its carcinogenic mechanism, Cr(VI) causes DNA double strand breaks and break-repair deficiency, leading to the development of chromosome instability. Therefore, the aim of this review is to discuss studies assessing Cr(VI)-induced DNA double strand breaks, chromosome damage and instability, and neoplastic transformation including cell culture, experimental animal, human pathology and epidemiology studies.</p><p><strong>Recent findings: </strong>Recent findings confirm Cr(VI) induces DNA double strand breaks, chromosome instability and neoplastic transformation in exposed cells, animals and humans, emphasizing these outcomes as key steps in the mechanism of Cr(VI) carcinogenesis. Moreover, recent findings suggest chromosome instability is a key phenotype in Cr(VI)-neoplastically transformed clones and is an inheritable and persistent phenotype in exposed cells, once more suggesting chromosome instability as central in the carcinogenic mechanism. Although limited, some studies have demonstrated DNA damage and epigenetic modulation are also key outcomes in biopsies from chromate workers that developed lung cancer. Additionally, we also summarized new studies showing Cr(VI) causes genotoxic and clastogenic effects in cells from wildlife, such as sea turtles, whales, and alligators. Overall, across the literature, it is clear that Cr(VI) causes neoplastic transformation and lung cancer. Many studies measured Cr(VI)-induced increases in DNA double strand breaks, the most lethal type of breaks clearly showing that Cr(VI) is genotoxic. Unrepaired or inaccurately repaired breaks lead to the development of chromosome instability, which is a common phenotype in Cr(VI) exposed cells, animals, and humans. Indeed, many studies show Cr(VI) induces both structural and numerical chromosome instability. Overall, the large body of literature strongly supports the conclusion that Cr(VI) causes DNA double strand breaks, inhibits DNA repair and chromosome instability, which are key to the development of Cr(VI)-induced cell transformation.</p>","PeriodicalId":10775,"journal":{"name":"Current Environmental Health Reports","volume":null,"pages":null},"PeriodicalIF":7.4000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Environmental Health Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40572-024-00460-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose of review: Hexavalent chromium [Cr(VI)] is a well-established human carcinogen, yet the mechanisms by which it leads to carcinogenic outcomes is still unclear. As a driving factor in its carcinogenic mechanism, Cr(VI) causes DNA double strand breaks and break-repair deficiency, leading to the development of chromosome instability. Therefore, the aim of this review is to discuss studies assessing Cr(VI)-induced DNA double strand breaks, chromosome damage and instability, and neoplastic transformation including cell culture, experimental animal, human pathology and epidemiology studies.
Recent findings: Recent findings confirm Cr(VI) induces DNA double strand breaks, chromosome instability and neoplastic transformation in exposed cells, animals and humans, emphasizing these outcomes as key steps in the mechanism of Cr(VI) carcinogenesis. Moreover, recent findings suggest chromosome instability is a key phenotype in Cr(VI)-neoplastically transformed clones and is an inheritable and persistent phenotype in exposed cells, once more suggesting chromosome instability as central in the carcinogenic mechanism. Although limited, some studies have demonstrated DNA damage and epigenetic modulation are also key outcomes in biopsies from chromate workers that developed lung cancer. Additionally, we also summarized new studies showing Cr(VI) causes genotoxic and clastogenic effects in cells from wildlife, such as sea turtles, whales, and alligators. Overall, across the literature, it is clear that Cr(VI) causes neoplastic transformation and lung cancer. Many studies measured Cr(VI)-induced increases in DNA double strand breaks, the most lethal type of breaks clearly showing that Cr(VI) is genotoxic. Unrepaired or inaccurately repaired breaks lead to the development of chromosome instability, which is a common phenotype in Cr(VI) exposed cells, animals, and humans. Indeed, many studies show Cr(VI) induces both structural and numerical chromosome instability. Overall, the large body of literature strongly supports the conclusion that Cr(VI) causes DNA double strand breaks, inhibits DNA repair and chromosome instability, which are key to the development of Cr(VI)-induced cell transformation.
审查目的:六价铬[Cr(VI)]是一种公认的人类致癌物质,但其致癌机制仍不清楚。六价铬致癌机制中的一个驱动因素是导致 DNA 双股断裂和断裂修复缺陷,从而导致染色体不稳定。因此,本综述旨在讨论评估六价铬诱导的 DNA 双股断裂、染色体损伤和不稳定性以及肿瘤转化的研究,包括细胞培养、实验动物、人类病理学和流行病学研究:最近的研究结果证实,六价铬会在暴露的细胞、动物和人体中诱导 DNA 双股断裂、染色体不稳定和肿瘤转化,并强调这些结果是六价铬致癌机制的关键步骤。此外,最近的研究结果表明,染色体不稳定性是六(Cr)新生物转化克隆的一个关键表型,也是暴露细胞中可遗传和持续存在的表型,这再次表明染色体不稳定性是致癌机制的核心。一些研究表明,DNA 损伤和表观遗传调控也是铬酸盐工人肺癌活组织检查的主要结果,尽管这些研究还很有限。此外,我们还总结了一些新的研究,这些研究表明六价铬会对海龟、鲸鱼和鳄鱼等野生动物的细胞产生遗传毒性和致畸作用。总之,从所有文献来看,六价铬显然会导致肿瘤转化和肺癌。许多研究测量了六(Cr)诱导的 DNA 双股断裂的增加,这种断裂是最致命的断裂类型,清楚地表明六(Cr)具有基因毒性。未修复或修复不准确的断裂会导致染色体不稳定,这是暴露于六价铬的细胞、动物和人类的常见表型。事实上,许多研究表明,六价铬会诱发染色体结构和数量上的不稳定性。总之,大量文献有力地支持了以下结论:六价铬会导致 DNA 双股断裂、抑制 DNA 修复和染色体不稳定,而这正是六价铬诱导细胞转化的关键所在。
期刊介绍:
Current Environmental Health Reports provides up-to-date expert reviews in environmental health. The goal is to evaluate and synthesize original research in all disciplines relevant for environmental health sciences, including basic research, clinical research, epidemiology, and environmental policy.