Influence of ozone and nitrogen dioxide on hepatic microsomal enzymes in mice.

Abstract

Since ambient concentrations of ozone and nitrogen dioxide increase drug-induced sleeping time in female mice, potential mechanisms were sought by investigating the effects of these gases on hepatic microsomal mixed-function oxidases in female CD-1 mice. A 3-h exposure to 9800 microgram O3/m3 (5 ppm) or 9400 microgram NO2/m3 (5 ppm) did not change the concentration of cytochrome P-450 significantly. Aniline hydroxylase, but not aminopyrine N-demethylase or p-nitroanisole O-demethylase, activities were increased following a 3-h exposure to 9400 microgram O3/m3 (5 ppm). Aniline hydroxylase activity was also increased after a 2-d (5 h/d) exposure to 1960 microgram O3/m3 (1 ppm). None of these enzyme activities were affected by a 3-h exposure to 9400 microgram NO2/m3 (5 ppm). In these studies, O3 sometimes increased wet liver weight, and thus additional experiments were conducted. A 5-h exposure to 1960 microgram O3/m3 (1 ppm) caused a lesser decrease in body weight than the decrease observed after a similar air exposure. Liver wet weights were elevated after O3 exposure. However, there were no significant changes in liver dry weight, liver dry-to-wet-weight ratio, or ratios of liver (wet or dry) weight to body weight. From these data, it is concluded that mechanisms other than those investigated are responsible for the effect of O3 and NO2 on drug-induced sleeping time. However, the activity of one mixed-function oxidase was slightly increased by O3, indicating a hitherto unrecognized systemic effect of O3 exposure.