A selective enhancement of xenobiotic metabolizing systems of rat lungs by prolonged exposure to ozone

Abstract

Male Wistar rats were exposed to 0.2 and 0.4 ppm O3 for 4, 8, and 12 weeks and to 0.1 and 0.2 ppm O3 for 4 weeks to examine the effects of prolonged exposure to O3 on the xenobiotic metabolizing systems in the lung. Exposures to 0.2 and 0.4 ppm O3 caused a significant increase in the NADPH-cytochrome P-450 reductase activity and cytochrome P-450 content in a dose-dependent manner during 4-12 weeks, whereas NADH-cytochrome b5 reductase was not altered. After 12 weeks of exposure to 0.4 ppm O3, NADPH-cytochrome P-450 reductase and cytochrome P-450 reached a maximum showing 138 (P less than 0.001) and 221% (P less than 0.001) those of the control levels, respectively. At 0.1 ppm O3, the cytochrome P-450 content still increased significantly to 152% that of the control on the fourth week. In parallel to the increment of cytochrome P-450 benzo(a)pyrene hydroxylase and 7-ethoxycoumarin O-deethylase increased significantly during 4-12 weeks of exposures to 0.2 and 0.4 ppm O3. After a 4-week exposure to 0.1 and 0.2 ppm O3, benzphetamine N-demethylase increased to the largest degree among the enzymes metabolizing four kinds of xenobiotics examined. 7-Ethoxycoumarin O-deethylase also increased significantly but of smaller magnitude, whereas coumarin hydroxylase was not affected. These results show that prolonged exposures to 0.1-0.4 ppm O3 persistently enhance pulmonary cytochrome P-450 systems. It is also suggested that some isozyme(s) of pulmonary cytochrome P-450, especially that catalyzing benzphetamine N-demethylation, are preferentially increased by exposure to low levels of O3.