Establishment and toxicological application of a cell line expressing human CYP2E1

Abstract

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 O3.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 < 0.05) and 74 % (P < 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.