Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats

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Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid(DMAV) is a major urinary metabolite of sodium arsenite(i As~Ⅲ) and induces urinary bladder cancers in rats. DMAVand i As~Ⅲare negative in in vitro mutagenicity tests. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMAVand i As~Ⅲin rat urinary bladder epithelium and liver using gpt delta F344 rats.Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0,92 mg/L DMAV, or 87 mg/L i As~Ⅲ(each 50 mg/L As) for 13 weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection(gpt assay) and deletion mutations are identified in the red/gam genes by Spi-selection(Spi-assay). Results of the gpt and Spi-assays showed that DMAVand i As~Ⅲhad no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMAVand i As~Ⅲare not mutagenic in urinary bladder epithelium or liver in rats. Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid (DMAV) is a major urinary metabolite of sodium arsenite (i As ~ III) and induces urinary bladder cancers in rats. However, their in vivo mutagenicities have not been determined. The purpose of present study is to evaluate the in vivo mutagenicities of DMAV and i As ~ III in rat urinary bladder epithelium and liver using gpt delta F344 rats.Ten-week old male gpt delta F344 rats were randomized into 3 groups and administered 0,92 mg / L DMAV, or 87 mg / L i As ~ III (each 50 mg / L As) for 13 weeks in the drinking water. In the mutation assay, point mutations are detected in the gpt gene by 6-thioguanine selection (gpt assay) and deletion mutations were identified in the red / gam genes by Spi-selection Spi-assays showed that DMAVand iAs ~ IIIhad no effects on the muta nt frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMAVand iAs ~ IIIare not mutagenic in urinary bladder epithelium or liver in rats.
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