The metabolic activation of dichloromethane and chlorofluoromethane in a bacterial mutation assay using Salmonella typhimurium

Abstract

The metabolic activation and mutagenicity of dichloromethane and chlorofluoromethane were investigated using rat liver fractions and Salmonella typhimurium strain TA100. Both dihalomethanes gave a mutagenic response without the addition of rat-liver fractions. This response has been shown to be due to bacterial metabolism of the test compounds by pathways believed to be similar to those known in the rat. When rat-liver post-mitochondrial supernatant was added to the mutagenicity assay, there was no significant increase in the mutagenicity of dichloromethane, whereas a 2-fold increase was observed for chlorofluoromethane under the same conditions. This increase was derived both from glutathione conjugation and cytochrome P450 oxidative dehydrochlorination. A significant increase in dichloromethane mutagenicity could only be achieved by increasing the concentration of post-mitochondrial supernatant. Under these conditions the increase in mutagenicity was derived solely from glutathione conjugation of dichloromethane. The difference in mutagenic response after the addition of rat-liver fractions can be explained by differences in the half lives of the reactive intermediates rather than a difference in overall metabolic rate between the two compounds.