INDUCTION AND INHIBITION OF CYTOCHROME P-450-DEPENDENT MONOOXYGENASESIN HAMSTER TISSUES BY ETHANOL

The effects of ethanol on hamster hepatic and extrahepatic monooxygena ses were determined in the present study. Chronic ethanol administrati on increased cytochrome P-450 (P-450) content and monooxygenase activi ties towards aniline, N-nitrosodimethylamine, and 7-ethoxyresorufin. I n contrast, benzphetamine and benzo(a)pyrene oxidation rates were decr eased 21-24% by ethanol. In kidney, ethanol pretreatment increased P-4 50 content, aniline and N-nitrosodimethylamine oxidation activities. I n lung, ethanol ingestion selectively increased aniline hydroxylation without affecting other monooxygenase activities. Intestinal monooxyge nase activity was refractory to ethanol induction. Immunoblotting of t he microsomal proteins showed that ethanol induced a protein cross-rea ctive with rabbit antibody raised against human P-450 2E1 in hamster l iver, kidney, and lung. Immunoblotting analysis using mouse monoclonal antibody 1-12-3 raised against scup P-450 1A1 revealed that ethanol i nduced an immunorelated protein in hamster liver, kidney, and lung. In duction of P-450 2E1 and 1A was not observed with intestinal protein b lots. Immunoblotting analysis using mouse monoclonal antibody 2-66-3 a gainst rat P-450 2B1 showed inhibition of an immunorelated protein in ethanol-treated hamster liver. The inhibitory effect on P-450 2B was n ot observed with extrahepatic tissues. These results suggest that etha nol has the ability to induce P-450s 2E1 and 1A and to inhibit P-450 2 B in hamster tissues.