Effect of 3-Methylcholanthrene on the Induction of Aryl Hydrocarbon Hydroxylase by Benz(A)Anthracene in Primary Cultures of Cutaneous Keratinocytes from the Newborn Rat

Abstract

The mixed-function oxidase, aryl hydrocarbon hydroxylase (AHH), is induced in primary cultures of cutaneous keratinocytes from the newborn rat grown in the presence 01 benz(a)anthracene (BA) or 3-methylcholanthrene (3-MC). The level of induction is 5–10 times greater from BA as compared with 3-MC. The addition of 5 μM 3-MC to the medium of cells being induced by 2.5 μM BA reduces the final specific activity of AHH to about half the level reached in the presence of BA alone. Higher concentrations of 3-MC can reduce the level of induction from BA to the maximum level achieved by 3-MC alone. The activity induced by BA is inhibited by 3-MC when added to the assay mixture. AHH induced by 3-MC is not so inhibited by 3-MC. BA does not appear to inhibit AHH induced by either polycyclic aromatic hydrocarbon. The 3-MC-mediatcd decrease in the level of active AHH produced in response to the presence of BA may be a function of repression of the inductive process, inhibition of the induced activity, or both.