EFFECT OF CHRONIC EXPOSURE TO OZONE AND NITRIC-ACID ON CYTOCHROME-P-450 MONOOXYGENASE SYSTEM OF RAT LUNG AND LIVER

Male F344/N rats were exposed to 0.15 ppm ozone (O-3) and 50 mu g/m(3) nitric acid (HNO3) vapor alone and in combination for 4 h/day, 3 days /wk for a total of 40 wk to investigate the effects of these environme ntal pollutants on cytochrome P-450 monooxygenases in pulmonary and he patic microsomes. Exposure to HNO3 vapor alone caused a significant in crease of 7-ethoxyresorufin O-deethylase (EROD) activity in the hepati c microsomes (p <.01). Immunoinhibition assays with monoclonal anti-cy tochrome P-450 (CYP) 1A1/1A2 (1-7-1) showed that the monoclonal antibo dy-inhibitable EROD activity in the hepatic microsomes was increased b y 59% (p <.01) and 40% (p <.05), respectively, in the HNO3 vapor and O -3 plus HNO3 vapor groups. Benzphetamine N-demethylase activity was no t significantly affected by exposure to either O-3 or HNO3 vapor in th e hepatic microsomes. However, in the lung O-3 exposure caused a 72% i ncrease in benzphetamine N-demethylase activity (p <.01). whereas this activity was decreased by 15% by HNO3 vapor exposure (p <.01). In the animals exposed to a combination of O-3 and HNO3 vapor, there was an 85% increase of benzphetamine N-demethylase activity in the lung (p <. 01). Total metabolism of H-3-benzo[a]pyrene was significantly increase d in the hepatic microsomes prepared from the animals exposed to O-3 ( p <.01), HNO3 vapor (p <.01), and O-3 plus HNO3 vapor (p <.05) groups compared to the air-exposed controls. Exposure to O-3, HNO3 vapor, and O-3 plus HNO3 vapor resulted in a 3- 5.4-; and 7.2-fold increase in t he metabolism of H-3-benzo[a]pyrene in the pulmonary microsomes (p <.0 1), suggesting that O-3 and HNO3 vapor may exert an additive action on the metabolism of H-3-benzo[a]pyrene in the lung.