Genetic Differences in Dimethylnitrosamine Mutagenicity in Vitro Associated with Mouse Hepatic Aryl Hydrocarbon Hydroxylase Activity Induced by 3‐Methylcholanthrene
- 1 February 1981
- journal article
- research article
- Published by Wiley in Acta Pharmacologica et Toxicologica
- Vol. 48 (2) , 118-128
- https://doi.org/10.1111/j.1600-0773.1981.tb01597.x
Abstract
The effects of 3-methylcholanthrene (MC) pretreatment on metabolism and mutagenic activation of [the carcinogen] dimethylnitrosamine (DMN) using the Ames (Salmonella) test were studied with liver subfractions from 2 strains of mice differing genetically with respect to aromatic hydrocarbon responsiveness. Both mutagenic activation and DMN N-demethylase activity segregated with aryl hydrocarbon (benzo[a]pyrene) hydroxylase activity as a dominant trait in appropriate crosses between C57BL/6J (Ahb Ahb) and DBA/2J (Ahd Ahd) mice. DMN metabolism and mutagenicity were increased by MC-pretreatment in responsive Ahb Ahb and Ahb Ahd mice, but not in non-responsive Ahd Ahd mice. This indicates the involvement of the Ah locus in the genetic regulation of these activities in mice. Deuteration of DMN reduced mutagenicity and DMN N-demethylase activity by approximately 90 and 50%, respectively.Keywords
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