Cell‐mediated mutagenesis of mammalian cells with chemical carcinogens

Abstract

Abstract Chemically non‐reactive carcinogens, such as polycyclic hydrocarbons, have to be metabolized by cellular enzymes in order to exert their biological effects including mutagenicity. Chinese hamster V79 cells can be efficiently mutated from 8‐azaguanine susceptibility to resistance by N‐methyl‐N‐nitro‐N‐nitrosoguanidine. But these cells do not metabolize polycyclic hydrocarbons and were therefore not mutated by these compounds. A system of cell‐mediated mutagenesis with carcinogenic hydrocarbons has been developed, by co‐cultivating V79 cells with lethally irradiated rodent cells that can metabolize the carcinogens. The number of mutations was dependent on the number of metabolizing cells and the carcinogens were not mutagenic when V79 cells were co‐cultivated with non‐metabolizing cells. Inhibition of the hydrocarbon metabolizing enzymes by 7,8‐benzoflavone, inhibited mutagenicity. Cell‐mediated mutagenicity was obtained with the carcinogenic hydrocarbons 7,12‐dimethylbenz (a)anthracene, benzo(a)pyrene and 3‐methylcholanthrene and there was no mutagenicity with the non‐carcinogenic hydrocarbon benz(a)anthracene. The degree of mutagenicity was related to the degree of carcinogenicity and the method detected mutagenicity with 0.1μg/ml. It is suggested that cell‐mediated mutagenesis with human cells should provide a useful system to test for environmental chemicals hazardous to humans that have to be metabolically activated.