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六价铬作业工人氧化 DNA 损伤与全基因组 DNA 低甲基化与叶酸缺乏有关。

Oxidative DNA damage and global DNA hypomethylation are related to folate deficiency in chromate manufacturing workers.

机构信息

Department of Clinical Laboratories, Third Hospital of Peking University, Beijing 100191, China.

出版信息

J Hazard Mater. 2012 Apr 30;213-214:440-6. doi: 10.1016/j.jhazmat.2012.02.024. Epub 2012 Feb 16.

Abstract

Exposure to hexavalent chromium [Cr (VI)] can cause DNA damage, genetic instability and increase the risk of cancer development. Folate deficiency affects DNA methylation and reduces the stability of the genetic material. However, the correlation between folate deficiency and DNA damage has never been clearly elucidated in chromate workers. In this study, we recruited one hundred and fifteen workers from chromate producing facilities as testing subjects and sixty local residents without chromium exposure history served as controls. The results showed an evident accumulation of Cr in peripheral red blood cells accompanied by a significantly decreased serum folate in chromate exposed workers. The decreased serum folate was associated with an increased urinary 8-hydroxy-2'-deoxyguanosine, DNA strand breaks and global DNA hypomethylation. These findings suggest that chronic occupational chromate exposure could induce folate depletion, which may further promote DNA damages and global DNA hypomethylation. Adequate folate supplement may provide benefit to chromate sufferers in stabilization of genetic material and reduce the risk of cancer development.

摘要

接触六价铬(Cr(VI))会导致 DNA 损伤、遗传不稳定性,并增加癌症发展的风险。叶酸缺乏会影响 DNA 甲基化并降低遗传物质的稳定性。然而,在铬酸盐工人中,叶酸缺乏与 DNA 损伤之间的相关性从未得到明确阐明。在这项研究中,我们招募了 115 名来自生产铬酸盐的设施的工人作为测试对象,60 名没有铬暴露史的当地居民作为对照。结果表明,铬暴露工人外周血红细胞中 Cr 明显蓄积,血清叶酸明显降低。血清叶酸的降低与尿 8-羟基-2'-脱氧鸟苷、DNA 链断裂和全基因组 DNA 低甲基化的增加有关。这些发现表明,慢性职业性铬酸盐暴露可导致叶酸耗竭,这可能进一步促进 DNA 损伤和全基因组 DNA 低甲基化。适当补充叶酸可能有益于稳定铬酸盐患者的遗传物质,降低癌症发展的风险。

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