EFFECTS OF MOTORCYCLE EXHAUST ON CYTOCHROME-P450-DEPENDENT MONOOXYGENASES AND GLUTATHIONE-S-TRANSFERASE IN RAT-TISSUES

The effects of motorcycle exhaust (ME) on cytochrome P-450 (P-450)-dep endent monooxygenases were determined using rats exposed to the exhaus t by either inhalation, intratracheal, or intraperitoneal administrati on. A 4-wk ME inhalation significantly increased benzo[a]pyrene hydrox ylation, 7-ethoxyresorufin O-deethylation, and NADPH-cytochrome c redu ctase activities in liver, kidney, and lung microsomes. Intratracheal instillation of organic extracts of ME particulate (MEP) caused a dose - and time-dependent significant increase of monooxygenase activity. I ntratracheal treatment with 0.1 g MEP extract/kg markedly elevated ben zo[a]pyrene hydroxylation and 7-ethoxyresorufin O-deethylation activit ies in the rat tissues 24 h following treatment. Intraperitoneal treat ment with 0.5 g MEP extract/kg/d for 4 d resulted in significant incre ases of P-450 and cytochrome b(5) contents and NADPH-cytochrome c redu ctase activity in liver microsomes. The intraperitoneal treatment also markedly increased monooxygenases activities toward methoxyresorufin in liver, kidney and lung. Immunoblotting analyses of microsomal prote ins using a mouse monoclonal antibody (Mab) 1-12-3 against rat P-450 1 A1 revealed that ME inhalation, MEP intratracheal, or MEP intraperiton eal treatment increased a P-450 1A protein in the hepatic and extra-he patic tissues. Protein blots analyzed using antibodies to P-450 enzyme s showed that MEP intraperitoneal treatment caused increases of P-450 2B, 2E, and 3A subfamily proteins in the liver. The ME inhalation, MEP intratracheal, or MEP intraperitoneal treatment resulted in significa nt increases in glutathione S-transferase activity in liver cytosols. The present study shows that ME and MEP extract contain substances tha t can induce multiple forms of P-450 and glutathione S-transferase act ivity in the rat.