Effects of nitrogen dioxide and ozone in combination on xenobiotic metabolizing activities of rat lungs

Abstract

Male Jcl: Wistar rats were exposed continuously to 0.2 ppm ozone (O 3) and 4 ppm nitrogen dioxide (NO 2), alone and in combination, for 1 and 2 months to examine the effects of combined gas on the xenobiotic metabolizing systems of lung microsomes. The cytochrome P-450 content increased to 200% and 253% of the control values during 2-month exposures to O 3, while it was not increased by NO 2 exposures. Addition of NO 2 to O 3 reduced the increased level of cytochrome P-450 to 179% and 178% of the control values. The activities of cytochrome P-450-dependent monooxygenase, benzo[ a]pyrene hydroxylase and 7-ethoxy-coumarin O-deethylase were changed in the same fashion by exposures to NO 2 and O 3. The 7-ethoxycoumarin O-deethylase activity was increased to 147% and 142% of the control values by O 3 exposure, whereas it was decreased to 71% and 75% of the control values by NO 2 exposures. This activity was decreased to 124% and 97% of the control values by combination of O 3 with NO 2 after 1 and 2 months, respectively. Similarly, the benzo[ a]pyrene hydroxylase activity was increased to 157% and 153% of the control values during O 3 exposures, while it was not changed by NO 2 exposures. Addition of NO 2 to O 3 reduced the activity to 140% and 115% of the control values after 1 and 2 months, respectively. The alteration of coumarin hydroxylase activity was different from those of others. This activity decreased to 44% and 29% of the control values after 1- and 2-month exposures to NO 2, respectively, and was also decreased by O 3 exposures. However, the magnitude of decrease was not reinforced by combination of NO 2 with O 3. These results indicate that an increased level of xenobiotic metabolizing activity produced by O 3 exposures is lowered by combination with NO 2. These phenomena may be antagonistic effects of these gases on the xenobiotic metabolizing systems of lung microsomes.