Metabolic deactivation of mutagens in the Salmonella-microsome test

Abstract

THE Salmonella typhimurium/mammsilmn microsome test of Ames et al.¹ has provided a simple and sensitive short term assay for the detection of environmental mutagens. Moreover, there is excellent correlation between a positive reaction of the compounds so far tested in this prokaryotic test system and their carcinogenicity^2–4. Metabolic activation of precarcinogens is achieved by incubating, on Petri dishes, the compounds to be tested, the bacterial strains and liver homogenates together with a NADPH generating system¹. The opposite phenomenon, that is conversion from mutagenically active to inert compounds, is also widely known to occur in vivo^5,6 and inactivating enzymes have also been identified for some reactive metabolites⁷. However, the possibility of checking deactivation of the mutagenic potential of chemicals by means of the same in vitro system set up for metabolic activation has received little attention. The results reported here provide evidence that some compounds which are mutagenic per se for S. typhimurium can be partially or totally deactivated in the presence of liver homogenates. This possibility should be considered when results of the Salmonella/microsome assay are interpreted, and correlated with animal and epidemiological data.