title: A selective decrease in the xenobiotic metabolizing activity of rat lungs by nitrogen dioxide exposures.
abstract: Groups of male Wistar rats were continuously exposed to nitrogen dioxide (NO2) ranging from 1.2 to 15 ppm for 1 or 2 weeks to examine the dose-effect relationship between NO2 and the xenobiotic metabolizing activity of lung microsomes. The lung cytochrome P-450 decreased significantly after 1-week exposures to 10 and 15 ppm NO2 and showed a decreasing tendency after 2-week exposures to 6-10 ppm NO2. On the other hand, the cytochrome b5, NADPH-cytochrome P-450 reductase and NADH-cytochrome b5 reductase of lung microsomes were increased concomitant with increase in microsomal proteins during 2-week exposures to 6-10 ppm NO2. These results show that the lung cytochrome P-450 decreases preferentially upon exposure to NO2 at higher concentrations. The coumarin hydroxylase activity was the most sensitive to NO2 exposures among activities metabolizing 4 kinds of xenobiotics examined. The coumarin hydroxylase activity was decreased in a dose-dependent fashion to 67-10% of the control level by 2-week exposures to 1.2-6 ppm NO2 and became negligible at 10 ppm NO2. The 7-ethoxycoumarin O-deethylase activity was also decreased to 82-56% of the control level by 2-week exposures to 1.2-6 ppm NO2 and became a constantly reduced level at 10 ppm NO2. The benzo[a]pyrene hydroxylase activity was decreased by exposures to NO2 above 10 ppm, and the benzphetamine N-demethylase activity also decreased during 2-week exposures to 6-10 ppm NO2. These results indicate that exposures to NO2 above 1.2 ppm cause a consistent and preferential reduction in the activities of coumarin hydroxylase and 7-ethoxycoumarin O-deethylase of lung microsomes in a dose-dependent manner.
authors.affiliation: Basic Medical Sciences Division, National Institute for Environmental Studies, Ibaraki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Miura
mesh_terms: D015660:7-Alkoxycoumarin O-Dealkylase; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001579:Benzopyrene Hydroxylase / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D003579:Cytochrome Reductases / Q000378:metabolism; D042966:Cytochrome-B(5) Reductase; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport; D004790:Enzyme Induction / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D010105:Oxygenases / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000393:Air Pollutants; D065607:Cytochrome P-450 Enzyme Inhibitors; 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; C019781:benzphetamine N-demethylase; D010089:Oxidoreductases, N-Demethylating; D003579:Cytochrome Reductases; D042966:Cytochrome-B(5) Reductase; D009251:NADPH-Ferrihemoprotein Reductase; D009585:Nitrogen Dioxide