Cancer risk assessment for ingested arsenic species : Interdisciplinary approach to new mechanism of carcinogenesis

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Arsine is quickly metabolized to arsenite and then to dimethylarsinic acid (DMA) via monomethylarsonic acid (MMA) in humans. The best biomarker of inorganic arsenic (iAs) exposure is urinary iAs+MMA concentration. We developed an analytical method that used HPLC-ICP-MS together with HPLC-MS/MS, which could measure precisely an arsenic compound including the arsenosugar of seaweed. A carcinogenic action of DMA may be due to the arsine radicals produced through (CH_3)_2AsH, which is enzymatically reduced from (CH_3)_2As-SG. Dimethylarsinous acid inhibits not only formation of the normal mitotic spindle but cytokinesis and induces the formation of multinuclear cells. Dimethylmonothioarsinic acid (DMMTA) is produced from DMA by intestinal bacteria flora and DMMTA is an ultimate carcinogen in DMA-induced rat bladder carcinogesesis.