Effects of nitrogen dioxide and ozone in combination on xenobiotic metabolizing activities of rat lungs.
Male Jcl:Wistar rats were exposed continuously to 0.2 ppm ozone (O3) and 4 ppm nitrogen dioxide (NO2), 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 O3, while it was not increased by NO2 exposures. Addition of NO2 to O3 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-ethoxycoumarin O-deethylase were changed in the same fashion by exposures to NO2 and O3. The 7-ethoxycoumarin O-deethylase activity was increased to 147% and 142% of the control values by O3 exposure, whereas it was decreased to 71% and 75% of the control values by NO2 exposures. This activity was decreased to 124% and 97% of the control values by combination of O3 with NO2 after 1 and 2 months, respectively. Similarly, the benzo[a]pyrene hydroxylase activity was increased to 157% and 153% of the control values during O3 exposures, while it was not changed by NO2 exposures. Addition of NO2 to O3 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 NO2, respectively, and was also decreased by O3 exposures. However, the magnitude of decrease was not reinforced by combination of NO2 with O3. These results indicate that an increased level of xenobiotic metabolizing activity produced by O3 exposures is lowered by combination with NO2. These phenomena may be antagonistic effects of these gases on the xenobiotic metabolizing systems of lung microsomes.
Takahashi
Y
Y
Basic Medical Sciences Division, National Institute for Environmental Studies, Ibaraki, Japan.
Miura
T
T
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010105:Oxygenases / Q000378:metabolism; D010126:Ozone / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D015262:Xenobiotics / Q000378:metabolism*
D015262:Xenobiotics; D010126:Ozone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D009585:Nitrogen Dioxide