A possible role for chromium(III) in genotoxicity.
A possible role for chromium(III) in genotoxicity.
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DOI：
10.1289/ehp.919275
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发表时间：
1991-05
影响因子：
10.4
通讯作者：
Snow ET
中科院分区：
文献类型：
--
作者：
Snow ET
铬主要以两种形式存在于环境中：还原的CrIII和CrVI，即铬酸盐。铬酸盐是最具生物活性的物质，很容易被活细胞吸收，并通过活性中间体在细胞内还原为稳定的中区填海第三期工程物质。CrIII是环境中含量最多的铬，不易穿过细胞膜，在体内相对不活跃。然而，细胞内的CrIII可以与核酸和蛋白质缓慢反应，并可能具有遗传毒性。我们利用DNA复制实验在体外研究了CrIII的遗传毒性，并通过cacl2介导的将铬处理的DNA转染到大肠杆菌中在体内研究了CrIII的遗传毒性。当使用纯化的DNA聚合酶（细菌或哺乳动物）在经过criii处理的模板上测量DNA复制时，DNA复制率和每个聚合酶结合事件的掺入量（处理率）都比对照组大大增加。当转染到大肠杆菌时，经criiii处理的M13mp2噬菌体DNA显示出突变频率的剂量依赖性增加。这些结果表明，CrIII改变了DNA模板与聚合酶之间的相互作用，从而增加了DNA聚合酶的结合强度，降低了DNA复制的保真度。这些相互作用可能有助于铬离子在体内的致突变性，并提示CrIII可以促进铬介导的致癌作用。
Chromium is found in the environment in two major forms: reduced CrIII and CrVI, or chromate. Chromate, the most biologically active species, is readily taken up by living cells and reduced intracellularly, via reactive intermediates, to stable CrIII species. CrIII, the most abundant form of chromium in the environment, does not readily cross cell membranes and is relatively inactive in vivo. However, intracellular CrIII can react slowly with both nucleic acids and proteins and can be genotoxic. We have investigated the genotoxicity of CrIII in vitro using a DNA replication assay and in vivo by CaCl2-mediated transfection of chromium-treated DNA into Escherichia coli. When DNA replication was measured on a CrIII-treated template using purified DNA polymerases (either bacterial or mammalian), both the rate of DNA replication and the amount of incorporation per polymerase binding event (processivity) were greatly increased relative to controls. When transfected into E. coli, CrIII-treated M13mp2 bacteriophage DNA showed a dose-dependent increase in mutation frequency. These results suggest that CrIII alters the interaction between the DNA template and the polymerase such that the binding strength of the DNA polymerase is increased and the fidelity of DNA replication is decreased. These interactions may contribute to the mutagenicity of chromium ions in vivo and suggest that CrIII can contribute to chromium-mediated carcinogenesis.