Vinyl chloride dependent mutagensis: effects of liver extracts and free radicals

The mutagenic effects of vinyl chloride (VC) on Salmonella typhimurium strain TA1530 are enhanced by mouse or rat liver extracts. The extracts prepared from mice pretreated either with vinyl chloride or the microsomal enzyme inducer, Aroclor 1254, did not produce any greater stimulation of VC-dependent mutagenesis than extracts from untreated animals. These same extracts, however, differed markedly in their capacity to stimulate the mutagenicity of dimethylnitrosamine (DMN), a compound which is converted to a mutagen by an NADPH dependent microsomal mixed function oxidase. The order of activity of the extracts with DMN was Aroclor pretreated is greater than untreated is greater than VC pretreated. Furthermore, the stimulatory effect of the liver extracts on VC mediated mutagenesis did not require NADPH and was still evident in liver extracts in which the microsomal mixed function oxidase system had been heat inactivated. The mutagenic activity of VC also was found to be stimulated by riboflavin in the presence of light suggesting that free radicals may be involved in VC dependent mutagenesis.