Mutagenicity of dimethylnitrosamine and ethyl methanesulfonate as determined by the host-mediated CHO/HGPRT assay.
Host-mediated assays have been developed to allow determination of the mutagenic potential of promutagens and procarcinogens which require metabolic activation to exert their effects on indicator organisms. We report here the development of the host-(mouse)-mediated CHO/HGPRT system using the procarcinogen dimethylnitrosamine (DMN) as a model agent. Using a 2--h treatment time, we observed a linear dose-response relationship up to 250 mg of DMN per kg body weight. At 100 and 500 mg/kg DMN, mutation induction increased with time up to at least 6 h. DMN was not mutagenic when tested in vitro. Athymic (nude) mice, their phenotypically normal littermates, or BALB/c mice of both sexes were found to be suitable as hosts. A time- and dose-dependency of induced mutation frequency by a direct-acting agent, ethyl methanesulfonate (EMS), was observed in both the in vitro and the host-mediated assays.
D000818:Animals; D002999:Clone Cells; D004128:Dimethylnitrosamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005020:Ethyl Methanesulfonate / Q000494:pharmacology*; D005260:Female; D005821:Genetic Techniques; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008698:Mesylates / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009153:Mutagens; D009602:Nitrosamines / Q000494:pharmacology*
D008698:Mesylates; D009153:Mutagens; D009602:Nitrosamines; D005020:Ethyl Methanesulfonate; D007041:Hypoxanthine Phosphoribosyltransferase; D004128:Dimethylnitrosamine