Effect of Chronic Exposure to Ozone and Nitric Acid on Cytochrome P-450 Monooxygenase System of Rat Lung and Liver

Abstract

Male F344/N rats were exposed to 0.15 ppm ozone (O₃) and 50 μg/m³ 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 environmental pollutants on cytochrome P-450 monooxygenases in pulmonary and hepatic microsomes. Exposure to HNO₃ vapor alone caused a significant increase of 7-ethoxyresorufin O-deethylase (EROD) activity in the hepatic microsomes (p < .01). Immunoinhibition assays with monoclonal anti-cytochrome P-450 (CYP) 1A1/1A2 (1-7-1) showed that the monoclonal antibody-inhibitableEROD activity in the hepatic microsomes was increased by 59% (p < .01) and 40% (p < .05), respectively, in the HNO₃ vapor and O₃ plus HNO₃ vapor groups. Benzphetamine N-demethylase activity was not significantly affected by exposure to either O₃ or HNO₃ vapor in the hepatic microsomes. However, in the lung, O₃ exposure caused a 72% increase 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 O₃ and HNO₃ vapor, there was an 85% increase of benzphetamine N-demethylase activity in the lung (p < .01). Total metabolism of ³H-benzo[a]pyrene was significantly increased in the hepatic microsomes prepared from the animals exposed to O₃ (p < .01), HNO₃ vapor (p < .01), and O₃ plus HNO₃ vapor (p < .05) groups compared to the air-exposed controls. Exposure to O₃ HNO₃ vapor, and O₃ plus HNO₃ vapor resulted in a 3-, 5.4-, and 7.2-fold increase in the metabolism of ³H-benzo[a]pyrene in the pulmonary microsomes (p < .01), suggesting that O₃ and HNO₃ vapor may exert an additive action on the metabolism of ³H-benzo[a]pyrene in the lung.