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Oxidation state specific analysis of arsenic species in tissues of wild-type and arsenic(+3 oxidation state)methyltransferase-knockout mice

查看全文 作　　者：Jenna [1]M.Currier;Christelle [2]Douillet;Zuzana [2]Drobná;Miroslav [1,2]Styblo 高影响力作者 机构地区：[1]Curriculum in Toxicology, University of North Carolina at Chapel Hill;[2]Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill高影响力机构 出　　处：《Journal of Environmental Sciences》索引2016年第28卷第11期,共9页高影响力期刊 基　　金：supported by NIH grant No. 2 R01 ES010845 to M.S.;the UNC Nutrition Obesity Research Center grant no. DK056350,;NIH grant No. P30ES010126 to the UNC Center for Environmental Health and Susceptibility;supported by a pre-doctoral traineeship (National Research Service Award T32 ES007126) from the National Institute of Environmental Health Sciences, NIH 摘　　要：Arsenic methyltransferase(As3mt) catalyzes the conversion of inorganic arsenic(i As) to its methylated metabolites, including toxic methylarsonite(MAs~Ⅲ) and dimethylarsinite(DMAs~Ⅲ). Knockout(KO) of As3 mt was shown to reduce the capacity to methylate i As in mice. However, no data are available on the oxidation states of As species in tissues of these mice. Here, we compare the oxidation states of As species in tissues of male C57BL/6 As3mt-KO and wild-type(WT) mice exposed to arsenite(iA s~Ⅲ) in drinking water. WT mice were exposed to50 mg/L As and As3mt-KO mice that cannot tolerate 50 mg/L As were exposed to 0, 15, 20, 25 or30 mg/L As. iA s~Ⅲaccounted for 53% to 74% of total As in liver, pancreas, adipose, lung, heart, and kidney of As3mt-KO mice; tri- and pentavalent methylated arsenicals did not exceed 10% of total As. Tissues of WT mice retained iA s and methylated arsenicals: iA s~Ⅲ, MAs~Ⅲand DMAs~Ⅲ represented 55%‐68% of the total As in the liver, pancreas, and brain. High levels of methylated species, particularly MAs~Ⅲ, were found in the intestine of WT, but not As3mt-KO mice,suggesting that intestinal bacteria are not a major source of methylated As. Blood of WT mice contained significantly higher levels of As than blood of As3mt-KO mice. This study is the first to determine oxidation states of As species in tissues of As3mt-KO mice. Results will help to design studies using WT and As3mt-KO mice to examine the role of iA s methylation in adverse effects of iA s exposure. 关 键 词：基因敲除 无机砷 氧化态 野生型 甲基转移酶 小鼠 组织 体分析
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