In vivo effects of nitrogen dioxide and ozone on xenobiotic metabolizing systems of rat lungs.

Male Jcl:Wistar rats were exposed continuously to either ozone (O3) or nitrogen dioxide (NO2) for 7 and 14 days to examine the effects of these gases on the xenobiotic metabolizing systems of lung microsomes. Exposure to 0.2 and 0.4 ppm O3 increased NADPH-cytochrome P-450 reductase activity and cytochrome P-450 as well as microsomal protein by the 14th day, whereas NADH-cytochrome b5 reductase was not affected. The most marked increase was observed in cytochrome P-450. In parallel to this increment, the activities of benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase of exposed animals increased significantly on the 7th and 14th days of exposure to 0.2 and 0.4 ppm 03. In contrast, exposure to 1.2 and 4 ppm NO2 decreased cytochrome P-450 on the 7th day. Moreover, the 7-ethoxycoumarin O-deethylase activity in exposed animals decreased to 61% (P less than 0.05) and 74% (P less than 0.001) of control on the 7th and 14th days of exposure to 4 ppm NO2, respectively. This decrease occurred in a dose-dependent manner with exposure to 0.4-4.0 ppm NO2, whilst benzo(a)pyrene hydroxylase activity was not affected. These results show that O3 at low doses induces xenobiotic metabolizing activities in the lung, whereas NO2 reduces this.