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

摘要

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid (DMA(V)) is a major urinary metabolite of sodium arsenite (iAs(III)) and induces urinary bladder cancers in rats. DMA(V) and iAsIII are 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 DMA(V) and iAs(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 DMA(V), or 87 mg/L iAs(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 DMA(V) and iAs(III) had no effects on the mutant frequencies or mutation spectrum in urinary bladder epithelium or liver. These findings indicate that DMAV and iAs(III) are not mutagenic in urinary bladder epithelium or liver in rats. (C) 2016 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V.