Mutagenicity of dimethylated metabolites of inorganic arsenics

The genotoxic effects of dimethylarsinic acid (DMAA), one of the main metabolites of inorganic arsenics in mammals, and its further metabolites were investigated using Escherichia coli B tester strains. When H/r30R (wild-type; Exc+Rec+) and Hs30R (uvrA-; Exc-Rec+) cells were incubated with DMAA for 3 h in liquid NB medium, many more revertants appeared in sealed tubes than in the control, but this was not the case in unsealed tubes, suggesting that volatile metabolites of DMAA caused the mutagenesis. By gas chromatography-mass spectrometry (GC-MS), dimethylarsine and trimethylarsine, known to be volatile metabolites in microorganisms, were detected in the gas phase of DMAA-added tester strain cell suspensions in sealed tubes. Among these arsines, dimethylarsine was mutagenic in WP2 (wild-type; Exc+Rec+) and WP2uvrA (uvrA-; Exc-Rec+), while trimethylarsine was not. The mutagenesis induced by dimethylarsine required oxygen gas in the assay system; the number of revertants markedly increased in an oxygen-replaced system and diminished in a nitrogen-replaced one. These results suggest that the reaction product(s) between dimethylarsine and molecular oxygen is responsible for the mutagenesis. The significance of this mutagenesis in the genetoxic action of inorganic arsenics is discussed.