In vitro metabolic activation of chemical mutagens II. The relationships among mutagen formation, metabolism and carcinogenicity for dimethylnitrosamine and diethylnitrosamine in the livers, kidneys and lungs of BALB/cJ, C 57BL/6J and RF/J mice

Abstract

The metabolic activation of dimethylnitrosamine (DMNA) and diethylnitrosamine (DENA) to mutagenic intermediates was studied using an in vitro genetic assay which measured the relative concentration and rate of formation of the active intermediates. Microsomal preparations from the livers, lungs and kidneys of BALB/cJ, C 57BL/6J and RF/J male mice were compared for their ability to activate the two carcinogens to mutagens. It was demonstrated that quantitative differences in activation could be detected between organs of the three strains and that different organs have characteristic activation kinetics. Activation kinetics for microsomal metabolism of DMNA by liver, lung and kidney tissues of male and female C 57BL/6J mice were also compared. Except for the female kidney preparations which appeared to lack the ability to activate DMNA and DENA, the activation properties for the male and female organs were quite similar. The results from this investigation tend to support the hypothesis that a single activated metabolite of DMNA is responsible for both its carcinogenic and mutagenic properties.