Mutagenicity of arsenic in mammalian cells: Role of reactive oxygen species
Mutagenicity of arsenic in mammalian cells: Role of reactive oxygen species
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DOI：
10.1073/pnas.95.14.8103
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发表时间：
1998-07-07
影响因子：
11.1
通讯作者：
Waldren, C
中科院分区：
文献类型：
--
作者：
Hei, TK;Liu, SX;Waldren, C
亚砷酸盐是环境中存在的三价砷，是一种已知的人类致癌物，在细菌和标准哺乳动物细胞突变检测中缺乏诱变活性。我们在这里表明，当在一种既可检测到基因内突变又可检测到多位点突变的试验(A(L)细胞试验)中进行评估时，亚砷酸盐实际上是一种强烈的剂量依赖性诱变剂，它主要诱导大的缺失突变。氧自由基清除剂二甲基亚砜与细胞共处理可显著降低亚砷酸盐的致突变性。因此，亚砷酸盐的致癌性至少可以部分解释为它是一种依赖于活性氧活性的诱变剂。
Arsenite, the trivalent form of arsenic present in the environment, is a known human carcinogen that lacked mutagenic activity in bacterial and standard mammalian cell mutation assays. We show herein that when evaluated in an assay (A(L) cell assay), in which both intragenic and multilocus mutations are detectable, that arsenite is in fact a strong dose-dependent mutagen and that it induces mostly large deletion mutations. Cotreatment of cells with the oxygen radical scavenger dimethyl sulfoxide significantly reduces the mutagenicity of arsenite. Thus, the carcinogenicity of arsenite can be explained at least in part by it being a mutagen that depends on reactive oxygen species for its activity.