Mutability of different genetic loci in mammalian cells by metabolically activated carcinogenic polycyclic hydrocarbons.
The relationship between carcinogenesis and mutagenesis in mammalian cells has been determined with 10 polycyclic hydrocarbons with different degrees of carcinogenicity. Mutagenesis was determined in Chinese hamster cells with genetic markers that affect the surface membrane, nucleic-acid synthesis, and protein synthesis. The mutations were characterized by resistance to ouabain, 8-azaguanine, and temperature. Mutagenesis by the carcinogens required metabolic activation and this was provided by the presence of lethally irradiated metabolizing cells. The degree of carcinogenicity was related to the degree of mutagenicity for all three genetic markers. The most potent carcinogen, 7,12-dimethylbenz[a]anthracene, gave the highest mutagenicity and mutagenicity was obtained with 0.01 mug/ml. Treatment of the cells with aminophylline, which increases polycyclic hydrocarbon metabolism, increased mutagenesis by the carcinogens. It is suggested that such an experimental system with these and other mammalian cells should be useful as a sensitive assay for hazardous environmental chemicals.
D000628:Aminophylline / Q000494:pharmacology; D001375:Azaguanine; D001580:Benzopyrenes / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D004351:Drug Resistance; D009153:Mutagens; D009696:Nucleic Acids / Q000096:biosynthesis; D010042:Ouabain / Q000494:pharmacology; D011083:Polycyclic Compounds; D014176:Protein Biosynthesis; D013696:Temperature
D001580:Benzopyrenes; D002273:Carcinogens; D009153:Mutagens; D009696:Nucleic Acids; D011083:Polycyclic Compounds; D000628:Aminophylline; D010042:Ouabain; D001375:Azaguanine