Inhibition of arylhydrocarbon hydroxylase and cytochrome P-450 by 20-methylcholanthrene and phenobarbital in guinea pig on excessive doses of ascorbic acid.

Treatment of guinea pigs on adequate ascorbic acid (AA) with 20-methylcholanthrene (MCA) and phenobarbital (PB) significantly increased hepatic arylhydrocarbon hydroxylase (AHH), cytochrome P-450 and cytochrome-b5 activities. In lungs, only MCA treatment significantly enhanced the activities of AHH, cytochrome P-450 and cytochrome b5. In animals on excessive doses of AA, there was inhibition of hepatic AHH, cytochrome P-450 and cytochrome b5 levels by treatment with these xenobiotics. Also, inhibition was observed in pulmonary AHH and cytochrome P-450 levels. The relevance of these observations in excessive AA-fed guinea pigs to carcinogenesis requires further extensive investigations.