Department of Environmental Medicine, New York University School of Medicine, 341 East 25 Street, New York, NY 10016, United States of America.
Toxicol Appl Pharmacol. 2019 Aug 15;377:114636. doi: 10.1016/j.taap.2019.114636. Epub 2019 Jun 20.
Chromium (Cr) is a naturally occurring metallic element found in the Earth's crust. While trivalent chromium ([Cr(III)] is considered non-carcinogenic, hexavalent chromium [Cr(VI)] has long been established as an IARC class I human carcinogen, known to induce cancers of the lung. Current literature suggests that Cr(VI) is capable of inducing carcinogenesis through both genetic and epigenetic mechanisms. Although much has been learned about the molecular etiology of Cr(VI)-induced lung carcinogenesis, more remains to be explored. In particular, the explicit epigenetic alterations induced by Cr(VI) in lung cancer including histone modifications and miRNAs, remain understudied. Through comprehensive review of available literature found between 1973 and 2019, this article provides a summary of updated understanding of the molecular mechanisms of Cr(VI)-carcinogenesis. In addition, this review identifies potential research gaps in the areas of histone modifications and miRNAs, which may prompt new niches for future research.
铬(Cr)是地壳中自然存在的金属元素。三价铬([Cr(III)]被认为是非致癌的,而六价铬[Cr(VI)]长期以来一直被国际癌症研究机构(IARC)列为 I 类人类致癌物,已知会导致肺癌。目前的文献表明,Cr(VI)能够通过遗传和表观遗传机制诱导致癌。尽管人们已经了解了 Cr(VI)诱导肺癌发生的分子病因学,但仍有许多方面需要探索。特别是,Cr(VI)在肺癌中诱导的明确的表观遗传改变,包括组蛋白修饰和 miRNAs,仍研究不足。通过对 1973 年至 2019 年间的现有文献进行全面回顾,本文总结了对 Cr(VI)致癌作用的分子机制的最新认识。此外,本综述确定了组蛋白修饰和 miRNAs 领域的潜在研究空白,这可能为未来的研究提供新的方向。