Raml Reingard, Raber Georg, Rumpler Alice, Bauernhofer Thomas, Goessler Walter, Francesconi Kevin A
Institute of Chemistry, Analytical Chemistry, Karl-Franzens University Graz, Universitaetsplatz 1, 8010 Graz, Austria.
Chem Res Toxicol. 2009 Sep;22(9):1534-40. doi: 10.1021/tx900158h.
We report studies on the variability in human metabolism of an oxo-arsenosugar involving the ingestion of a chemically synthesized arsenosugar and quantitative determination of the arsenic metabolites in urine and serum by HPLC coupled with arsenic-selective mass spectrometric detection (ICPMS, inductively coupled plasma mass spectrometry). The total, four-day, urinary excretion of arsenic for six volunteers ranged widely from ca. 4-95%. The arsenic metabolites present in the urine also showed great variability: high arsenic excretion was accompanied by almost complete biotransformation of the ingested oxo-arsenosugar into a multitude of metabolites (>10), whereas the subjects that excreted low amounts of arsenic produced low quantities of metabolites relative to unchanged oxo-arsenosugar and its thio-analogue. Major arsenic urinary metabolites were dimethylarsinate (DMA) and possible intermediates in the degradation of arsenosugar to DMA, namely, dimethylarsinoylethanol (DMAE) and dimethylarsinoylacetate (DMAA) present both as their oxo- and thio-analogues. Thio-DMAE and thio-DMAA were also found in blood serum indicating that these species were formed in the liver rather than on storage of the urine in the bladder. The large variability in the way individuals metabolize arsenosugars has implications for risk assessment of arsenic intake from seafood.
我们报告了关于一种氧代砷糖在人体代谢变异性的研究，该研究涉及摄入化学合成的砷糖，并通过高效液相色谱与砷选择性质谱检测（电感耦合等离子体质谱法，ICPMS）联用对尿液和血清中的砷代谢物进行定量测定。六名志愿者四天内砷的总尿排泄量差异很大，范围约为4% - 95%。尿液中存在的砷代谢物也表现出很大的变异性：高砷排泄伴随着摄入的氧代砷糖几乎完全生物转化为多种代谢物（>10种），而排泄少量砷的受试者相对于未改变的氧代砷糖及其硫代类似物产生的代谢物数量较少。主要的尿砷代谢物是二甲基砷酸（DMA）以及砷糖降解为DMA过程中的可能中间体，即二甲基砷酰乙醇（DMAE）和二甲基砷酰乙酸（DMAA），它们均以氧代和硫代类似物的形式存在。血清中也发现了硫代 - DMAE和硫代 - DMAA，这表明这些物质是在肝脏中形成的，而不是在尿液储存在膀胱时形成的。个体代谢砷糖方式的巨大变异性对评估从海鲜中摄入砷的风险具有重要意义。
