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六价铬诱导的DNA损伤与修复机制。

Hexavalent chromium-induced DNA damage and repair mechanisms.

作者信息

Wise Sandra S, Holmes Amie L, Wise John Pierce

机构信息

Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, University of Southern Maine, Portland, Maine 04104-9300, USA.

出版信息

Rev Environ Health. 2008 Jan-Mar;23(1):39-57. doi: 10.1515/reveh.2008.23.1.39.

Abstract

Hexavalent chromium is a commonly used industrial metal that has been shown to induce lung cancer in workers having long term exposure. In the particulate form, Cr(VI) dissolves slowly in vivo, leading to an extended exposure of lung cells. Hexavalent chromium is taken into the cell and rapidly reduced to Cr(V), Cr(IV), Cr(III), and reactive oxygen species. Cells treated with Cr(VI) are subject to several types of DNA damage resulting from this reduction, including base modification, single-strand breaks, double-strand breaks, Cr-DNA adducts, DNA-Cr-DNA adducts, and protein-Cr-DNA adducts. These types of damage, if left unrepaired or are misrepaired, can lead to growth arrest, cytotoxicity, and apoptosis, as well as mutations leading to neoplastic transformation and ultimately tumorigenesis. Here we review the current literature on Cr-induced DNA damage and its repair.

摘要

六价铬是一种常用的工业金属,长期接触该金属的工人已被证实会诱发肺癌。以颗粒形式存在的六价铬在体内溶解缓慢,导致肺细胞长期暴露。六价铬进入细胞后会迅速还原为五价铬、四价铬、三价铬和活性氧。经六价铬处理的细胞会因这种还原作用而遭受多种类型的DNA损伤,包括碱基修饰、单链断裂、双链断裂、铬-DNA加合物、DNA-铬-DNA加合物以及蛋白质-铬-DNA加合物。如果这些类型的损伤未得到修复或修复错误,可能会导致生长停滞、细胞毒性和细胞凋亡,以及导致肿瘤转化并最终引发肿瘤的突变。在此,我们综述了当前关于铬诱导的DNA损伤及其修复的文献。

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