Abstract
Groups of male Wistar rats were continuously exposed to nitrogen dioxide (NO 2) ranging from 1.2 to 15 ppm for 1 or 2 weeks to examine the dose-effect relationship between NO 2 and the xenobiotic metabolizing activity of lung microsomes. The lung cytochrome P-450 decrease significantly after 1-week exposures to 10 and 15 ppm NO 2 and showed a decreasing tendency after 2-week exposures to 6–10 ppm NO 2. On the other hand, the cytochrome b 5, NADPH-cytochrome P-450 reductase and NADH-cytochrome b 5 reductase of lung microsomes were increased concomitant with increase in microsomal proteins during 2-week exposures to 6–10 ppm NO 2. These results show that the lung cytochrome P-450 decreases preferentially upon exposure to NO 2 at higher concentrations. The coumarin hydroxylase activity was the most sensitive to NO 2 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 NO 2 and became negligible at 10 ppm NO 2. 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 NO 2 and became a constantly reduced level at 10 ppm NO 2. The benzo[ a]pyrene hydroxylase activity was decreased by exposures to NO 2 above 10 ppm, and the benzphetamine N-demethylase activity also decreased during 2-werk exposures to 6–10 ppm NO 2. These results indicate that exposures to NO 2 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.
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