Inorganic
arsenic (iAs) exposure has been associated with the increased risk of various forms of
cancer and of non-cancerous diseases. Metabolic conversions of iAs that yield highly toxic and genotoxic
methylarsonite (MAsIII) and
dimethylarsinite (DMAsIII) may play a significant role in determining the extent and character of toxic and
cancer-promoting effects of iAs exposure. However, in vivo research involving the production of MAsIII and DMAsIII remains an area of ongoing investigation and debate. The results of metabolic and toxicity studies using mice have been entirely applicable to other species including humans. The goal of this study was to investigate the phenotype for the trivalent and pentavalent
arsenic metabolites in relation to
arsenite dose via immediate analysis of fresh urine samples, while preventing the oxidation of unstable methylated AsIII-containing metabolites. Female mice (C57BL/6) received
sodium arsenite by gavage at doses of 0, 3, 6 or 10 mg As/kg/day for 9 days, after which trivalent methylated
arsenicals were detected in 100% of urine samples; these
arsenicals were not detected in the urine of control mice. The amount of DMAsIII detected in urine depended on the dose of
arsenite administered and was determined to be 50.2%, 31.4% and 16.5% of the total urinary
arsenic in mice exposed to 3, 6, or 10 mg/kg/day, respectively. This relationship is consistent with the hypothesis of inhibition or saturation of iAs methylation. Understanding the in vivo production of MAsIII and DMAsIII in mice exposed to iAs could aid in developing a biologically based dose-response model for iAs.