Role of active oxygen species in metal-induced DNA strand breakage in human diploid fibroblasts

Ronald D. Snyder
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引用次数: 97

Abstract

The ability of 6 metal salts to induce DNA damage in human diploid fibroblasts was examined. Cadmium, magnesium, manganese, chromium(VI), zinc and selenite were all shown to induce DNA strand breaks as measured by two independent assays. DNA strand breaks were repaired within 2–4 h after removal of metal and this repair appeared not to be sensitive to “long-patch” repair inhibitors. With the exception of selenite, metal-induced DNA damage appeared to be mediated via the formation of active oxygen species since oxygen scavengers when administered simultaneously with the metal, antagonized strand break formation. Selenite-induced DNA damage (as previously reported) was dependent on the formation of a selenite-glutathione conjugant and was not affected by oxygen radical scavengers. Scavenger treatment did not enhance cloning ability of metal-treated cells suggesting that DNA strand breaks may not be important in metal-induced cytotoxicity.

活性氧在金属诱导的人二倍体成纤维细胞DNA链断裂中的作用
研究了6种金属盐对人二倍体成纤维细胞DNA损伤的影响。镉,镁,锰,铬(VI),锌和亚硒酸盐都显示出诱导DNA链断裂,通过两个独立的测定。DNA链断裂在去除金属后2-4小时内修复,这种修复似乎对“长补丁”修复抑制剂不敏感。除亚硒酸盐外,金属诱导的DNA损伤似乎是通过活性氧的形成介导的,因为当氧清除剂与金属同时施用时,会拮抗链断裂的形成。亚硒酸盐诱导的DNA损伤(如先前报道)依赖于亚硒酸-谷胱甘肽缀合物的形成,不受氧自由基清除剂的影响。清道夫处理并没有提高金属处理细胞的克隆能力,这表明DNA链断裂在金属诱导的细胞毒性中可能并不重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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