DMPS–Arsenic Challenge Test: II. Modulation of Arsenic Species, Including Monomethylarsonous Acid (MMAIII), Excreted in Human Urine

Abstract 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.