Tissue differences in the ontogeny of inducibility of drug-metabolizing enzymes by 3-methylcholanthrene in the rabbit

Abstract

1. The effects of treatment of rabbits of different ages with 3-methylcholanthrene on cytochrome P-450 content, and benzo[a]pyrene hydroxylase, epoxide hydrolase, gluta-thione S-epoxide transferase, 1-naphthol glucuronyl transferase and morphine glucuronyl transferase activities of liver, kidney and lung have been investigated.

2. The cytochrome P-450 content of liver and kidney was inducible at all ages, whereas that of lung was inducible up to only seven days old. Benzo[a]pyrene hydroxylase activity was inducible more than two-fold in kidney at all ages, but in liver and lung up to only seven days old.

3. Epoxide hydrolase activity was inducible, only in liver and lung of younger animals, to an extent of < 50%.

4. Glutathione S-epoxide transferase activity was inducible, in the liver of young animals and in the kidney of adult animals, to extents of < 50%.

5. Both 1-naphthol and morphine glucuronly transferase activities were significantly induced in the liver of animals up to three days old, the former being induced to the greater extent. These enzymes were not studied in kidney or lung.

6. It is concluded that 3-methylcholanthrene treatment of rabbits has tissue-specific and age-specific effects on various drug-metabolizing enzyme.