COMPARISON OF THE CAPACITY OF FETAL AND ADULT LIVER, LUNG, AND BRAIN TO CONVERT POLYCYCLIC AROMATIC-HYDROCARBONS TO MUTAGENIC AND CYTOTOXIC METABOLITES IN MICE AND RATS

Preparations of S-9 (supernatant fractions of tissue homogenates centrifuged at 9000g for 10 min) fractions from the fetal brains of rats displayed a high capacity to convert 7,12-dimethylbenz(a)anthracene to metabolites mutagenic to Salmonella typhimurium tester strains TA-98, TA-100, and TA-1538. The same tissue was only minimally active or inactive in converting benzo(a)pyrene or N-2-fluorenylacetamide to mutagenic metabolites. Fetal brain tissues of mice were virtually inactive with respect to the bioactivation of each of the three procarcinogens but fetal pulmonary tissues of mice produced mutagen-generating activities that were five- to ninefold above background with respect to 7,12-dimethylbenz(a)anthracene. Fetal hepatic and brain tissues of mice also catalyzed the conversion of each of the three promutagens to cytotoxic intermediates but this phenomenon was not observed with fetal hepatic or brain tissues of rats. Analyses with high-pressure liquid chromatography demonstrated that brain tissues of fetal mice were very active in converting 7,12-dimethylbenz(a)anthracene to oxygenated metabolites whereas the fetal brain tissues of rats were only minimally active. The chromatographic patterns observed also indicated that different metabolites were formed in the presence of S-9 fractions from rats vs mice. The data are consistent with the hypothesis that the previously observed species difference in susceptibility to transplacental tumorigenesis by polycyclic hydrocarbons is related to differences in target organ biotransformation of these compounds. © 1979.