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） ...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.展开更多
基金supported by a Grant from the Food Safety Commission, Cabinet Office, Japan (Research Program for Risk Assessment Study on Food Safety, No. 1407)
文摘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.
