Studies on the efficiency of the Salmonella/rat hepatocyte assay for the detection of carcinogens as mutagens: activation of 1,2-dimethyl-hydrazine and procarbazine into bacterial mutagens.

Abstract

Aflatoxin B1, benzo[a]pyrene, N-nitrosomorpholine, procarbazine (PC) and 1,2-dimethylhydrazine (DMH) were used to investigate the efficiency of the Salmonella/rat hepatocyte assay for detecting carcinogens as mutagens. In this assay, bacteria and the test compound were co-incubated with freshly isolated rat hepatocytes and then plated onto minimal glucose agar. Factors for optimal mutagenicity, including the number of hepatocytes and the number of bacteria, the type of assay medium and the length of incubation in liquid medium were investigated. All the compounds were metabolized into bacterial mutagens. Mediation of the mutagenicity of PC and DMH by rat hepatocytes indicates that freshly isolated cells of this type are a useful alternative metabolic activation system for use in screening chemicals found to be non-mutagenic in the Salmonella/microsome assay.