DMPS -: Arsenic Challenge Test II.: Modulation of arsenic species, including monomethylarsonous acid (MMAIII), excreted in human urine
DMPS -: Arsenic Challenge Test II.: Modulation of arsenic species, including monomethylarsonous acid (MMAIII), excreted in human urine
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DOI：
10.1006/taap.2000.8922
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发表时间：
2000-05-15
影响因子：
3.8
通讯作者：
Titcomb, A
中科院分区：
文献类型：
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作者：
Aposhian, HV;Zheng, BS;Titcomb, A
对长期接触无机砷的人群给予2，3-二巯基-1-丙磺酸钠（DMPS）后，尿中砷排泄量增加，尿中出现并鉴定出一甲基亚胂酸（MMA（III）），尿中二甲基亚胂酸（DMA）的浓度和百分比显著降低。这是首次在尿液中检测到MMA（III）。然后设计并进行体外生化实验以了解MMA（III）的尿液外观和DMA的减少。DMPS-MMA（III）复合物作为MMA（III）甲基转移酶的底物没有活性。实验结果支持DMPS与MMA（III）的内源性配体竞争的假设，形成DMPS-MMA复合物，很容易在尿液中排泄，并指出需要研究MMA（III）的生化毒理学。应该强调的是，MMA（III）仅在DMPS给药后经尿液排泄。这些研究的结果提出了许多关于MMA（III）在无机砷毒性中的潜在中心作用以及MMA（III）在角化过度、色素沉着过度和癌症的病因学中的潜在参与的问题，这些病因学可能是由慢性无机砷暴露引起的，（C）2000学术出版社。
The administration of sodium 2,3-dimercapto-1-propane sulfonate (DMPS) to humans chronically exposed to inorganic arsenic in their drinking water resulted in the increased urinary excretion of arsenic, the appearance and identification of monomethylarsonous acid (MMA(III)) in their urine, and a large decrease in the concentration and percentage of urinary dimethylarsinic acid (DMA). This is the first time that MMA(III) has been detected in the urine. In vitro biochemical experiments were then designed and performed to understand the urinary appearance of MMA(III) and decrease of DMA. The DMPS-MMA(III) complex was not active as a substrate for the MMA(III) methyltransferase. The experimental results support the hypothesis that DMPS competes with endogenous ligands for MMA(III), forming a DMPS-MMA complex that is readily excreted in the urine and points out the need for studying the biochemical toxicology of MMA(III). It should be emphasized that MMA(III) was excreted in the urine only after DMPS administration. The results of these studies raise many questions about the potential central role of MMA(III) in the toxicity of inorganic arsenic and to the potential involvement of MMA(III) in the Little-understood etiology of hyperkeratosis, hyperpigmentation, and cancer that can result from chronic inorganic arsenic exposure, (C) 2000 Academic Press.