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In Vitro Metabolism and Microsome-mediated Mutagenicity of Dialkylnitrosamines in Rat, Hamster, and Mouse Tissues¹

International Agency for Research on Cancer, Unit of Chemical Carcinogenesis, 150, Cours Albert Thomas, 69008 Lyon, France

Rates of conversion of ¹⁴C-labeled dimethyl- and diethyl-nitrosamine by rat and hamster tissue slices to ¹⁴CO₂ and/or into mutagenic reactants were measured using Salmonella typhimurium G-46 or 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.

¹ Some of the data were presented at the Fourth meeting of the European Environmental Mutagen Society, Heidelberg, 1974.

² To whom correspondence should be addressed.

Received 6/10/74. Accepted 10/15/74.