In vitro versus in vivo metabolic activation of mutagens.

Abstract

Mutagenicity testing is beginning to find a place as a factor in evaluation of the safety of compounds to which the human population is exposed. The mutation systems selected for such tests should ideally involve in vivo studies with mammals and encompass scoring of a broad spectrum of mutational events including both transmissible chromosome aberrations and point mutations. The frequency of chromosome aberrations obtained after a certain treatment can be assessed quantitatively without prohibitive costs and effort. At the present time there is only one proven system which can be used to screen for specific locus mutations in mammals in vivo; the seven specific locus system of Russell. On the other hand there are many microbial systems in which point mutation frequencies can be easily determined quantitatively. It is a known fact, however, that mammals can convert nonmutagenic compounds (promutagens) to highly mutagenic metabolites and that these promutagens are not mutagenic in microorganisms (1). In order to combine the drug metabolism of the mammal with the excellence of the microbial systems for measuring point mutations, the host-mediated assay (1) and the microsomal system (2) were developed. In the host-mediated assay the