生物甲基化在砷的毒性和致癌性中的作用：研究进展
The role of biomethylation in toxicity and carcinogenicity of arsenic: a research update.
作者信息
Stýblo Miroslav, Drobná Zuzana, Jaspers Ilona, Lin Shan, Thomas David J
机构信息
Department of Pediatrics, Center for Environmental Medicine and Lung Biology, Burnett-Womack Clinical Sciences Building, University of North Carolina, Chapel Hill, NC 27599-7220, USA.
出版信息
Environ Health Perspect. 2002 Oct;110 Suppl 5(Suppl 5):767-71. doi: 10.1289/ehp.110-1241242.
Abstract
Recent research of the metabolism and biological effects of arsenic has profoundly changed our understanding of the role of metabolism in modulation of toxicity and carcinogenicity of this metalloid. Historically, the enzymatic conversion of inorganic arsenic to mono- and dimethylated species has been considered a major mechanism for detoxification of inorganic arsenic. However, compelling experimental evidence obtained from several laboratories suggests that biomethylation, particularly the production of methylated metabolites that contain trivalent arsenic, is a process that activates arsenic as a toxin and a carcinogen. This article summarizes this evidence and provides new data on a) the toxicity of methylated trivalent arsenicals in mammalian cells, b) the effects of methylated trivalent arsenicals on gene transcription, and c) the mechanisms involved in arsenic methylation in animal and human tissues.
摘要
近期关于砷的代谢及其生物学效应的研究，深刻改变了我们对于代谢在调节这种类金属毒性和致癌性中所起作用的理解。从历史角度来看，无机砷向一甲基化和二甲基化产物的酶促转化，一直被视作无机砷解毒的主要机制。然而，多个实验室获得的有力实验证据表明，生物甲基化，尤其是含有三价砷的甲基化代谢产物的生成，是一个将砷激活为毒素和致癌物的过程。本文总结了这些证据，并提供了关于以下方面的新数据：a）甲基化三价砷化合物在哺乳动物细胞中的毒性；b）甲基化三价砷化合物对基因转录的影响；c）动物和人体组织中砷甲基化所涉及的机制。
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