Chronic exposure to inorganic
arsenic (iAs) has been associated with increased risk of various forms of
cancer and of noncancerous 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. In this study we examined the relationship between urinary profiles of MAsIII and DMAsIII and skin lesion markers of iAs toxicity in individuals exposed to iAs in
drinking water. The study subjects were recruited among the residents of an endemic region of central Mexico.
Drinking-water reservoirs in this region are heavily contaminated with iAs. Previous studies carried out in the local populations have found an increased incidence of pathologies, primarily skin lesions, that are characteristic of arseniasis. The goal of this study was to investigate the urinary profiles for the trivalent and pentavalent As metabolites in both high- and low-iAs-exposed subjects. Notably, methylated trivalent
arsenicals were detected in 98% of analyzed urine samples. On average, the major metabolite, DMAsIII, represented 49% of total urinary As, followed by DMAsV (23.7%), iAsV (8.6%), iAsIII (8.5%), MAsIII (7.4%), and MAsV (2.8%). More important, the average MAsIII concentration was significantly higher in the urine of exposed individuals with skin lesions compared with those who drank iAs-contaminated water but had no skin lesions. These data suggest that urinary levels of MAsIII, the most toxic species among identified metabolites of iAs, may serve as an
indicator to identify individuals with increased susceptibility to toxic and
cancer-promoting effects of arseniasis.