In vitro metabolism and microsome-mediated mutagenicity of dialkylnitrosamines in rat, hamster, and mouse tissues.
Rates of conversion of 14C-labeled dimethyl-and diethylnitrosamine by rat and hamster tissue slices to 14CO2 and/or into mutagenic reactants were measured using Salmonella typhimurium G-46 r TA 1530 and fortified tissue fractions in vitro. A correlation between the CO2 production from dimethyl- or diethylnitrosamine in liver or lung and the organ distribution of induced tumors in vivo was observed. As an exception, hamster lung, which is a major target organ in diethylnitrosamine carcinogenesis, did not convert this nitrosamine into metabolites mutagenic for S. typhimurium TA 1530 although the 14CO2 production in vitro was even higher than in hamster liver. The effect of pretreating rats, hamsters, and mice with phenobarbitone on the mutation frequency produced by dimethyl-or diethylnitrosamine in in vitro assays was determined. The relationship between the site of metabolic activation, mutagenicity, and carcinogenicity of the dialkylnitrosamines and the effect of enzyme inducers are discussed.
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002876:Chromosomes, Bacterial / Q000187:drug effects; D006224:Cricetinae; D004790:Enzyme Induction; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008861:Microsomes / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D009153:Mutagens / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines / Q000378:metabolism*; D010101:Oxygen Consumption; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D012142:Respiratory Tract Neoplasms / Q000139:chemically induced; D012486:Salmonella typhimurium; D013045:Species Specificity
D009153:Mutagens; D009602:Nitrosamines; D002245:Carbon Dioxide; D006899:Mixed Function Oxygenases; D010634:Phenobarbital