Dose-response relationship of rat aryl hydrocarbon hydroxylase and epoxide hydratase induction.

Abstract

This paper summarizes our recent results supporting the hypothesis that different regulation mechanisms are involved in the control of AHH and EH activity and that the AHH induction in the extrahepatic tissues might also be affected by liver specific inducers. In the rat, lung and kidney AHH is highly sensitive to the inducers present in cigarette smoke and cigarette smoke condensate, the EH activity not being affected by the same agents. Phenobarbital is also able to potentiate the inducing action of low doses of benzo(a)pyrene on the lung AHH activity. In primary rat liver cells in culture, AHH and EH can be selectively induced. Low doses of benz(a)anthracene preferentially enhance the AHH activity while trans-stilbene oxide and various antioxidants modify only the EH activity. Phenobarbital, which also induces the AHH activity in cell culture, produces a more than additive effect when added to the culture medium in a mixture with benz(a)anthracene. Trans-stilbene oxide prevents the AHH induction by phenobarbital and not by benz(a)anthracene. Our results suggest that, in addition to its own induction capacity, phenobarbital is also able to potentiate the action of chemicals belonging to a different class of inducers.