Animal model for arsenic carcinoge

Abstract

Although inorganic arsenic is a well-known carcinogen associated with urinary bladder, liver, skin, and lung cancers in humans, the underlying mechanisms are not well understood, partly due to lack of appropriate animal models. We have demonstrated carcinogenicities of various organic metabolites of arsenic using various rat models. We showed for the first time that dimethylarsenic acid (DMA^V), a major metabolite of arsenic in humans, is a complete urinary bladder carcinogen, and exerts promotion effects on liver carcinogenesis in rats as well. In the comparison study of urinary bladder carcinogenicities of DMA^V with other arsenic compounds, we identified dimethylmonothioarsinic acid (DMMTA^V), a new urinary metabolite. Furthermore, we demonstrated that DMMTA^V is majorly produced from DMA^V by intestinal bacterial in colon and is an ultimate carcinogen in DMA^V-induced rat bladder carcinogenesis. Our findings provide experimental evidence for arsenic carcinogenicity and will facilitate both the understanding of the carcinogenic mechanisms of arsenic and the development of model in arsenic risk assessment.