Ontogeny of benzo(a)pyrene hydroxylase, epoxide hydrolase and glutathione-S transferase in the brain, lung and liver of C57Bl/6 mice.

Typical developmental patterns of three drug-metabolizing enzymes in C57Bl/6 mouse brain, lung and liver could be divided into three stages: stage I, at the end of intrauterine life, where an increase in enzymatic activity was observed; stage II, during the first days after birth, where a decrease was seen; and stage III from the 6th day until weaning, where there was a gradual increase, reaching the same values as in the adult animal. However, pulmonary benzo(a)pyrene hydroxylase activity showed an abrupt burst starting on day 6 of postnatal life, then decreased slowly to become steady, and finally increased again. Our data show that the major metabolic pathways catalyzed by glutathione-S transferase and epoxide hydrolase are operative in mouse fetal brain and lung, just as in liver. In addition, we show that enzymatic systems are inducible during fetal life by exogenous compounds such as 5,6-benzoflavone. The early developmental evolution of the drug-metabolizing enzymes should help understand feto-toxicological and teratological phenomena.