In vivo and in vitro inhibition of 3-methylcholanthrene-induced aryl hydrocarbon hydroxylase activity in rat liver by actinomycin D and 7,8-benzoflavone

Abstract

Using the very well investigated and sensitive microsomal monooxynogenase aryl hydrocarbon hydrolase (AHH), we investigated the dose-response relations between an inducer, 3-methylcholanthrene (3-MC), and an inhibitor of transcription, actinomycin D (ACT D), in 10 days old rats. An optimum pretreatment schedule proved to be a single dose of 1 to 40 mg/kg 3-MC ip combined with two administrations of 200 to 600 microgram/kg ACT D within 16 hr. With increasing doses of ACT D the inhibition of 3-MC-mediated AHH induction increased up to 88%. With 7,8-benzoflavone (ANF) as a relatively specific in vitro inhibitor of the cytochrome P-448 species no distinct influence on the constitutive AHH activity could be observed up to the 30th days of age. In 60 and 200 days old rats the inhibition reached a significant level of about 50%. After 3-MC induction a nearly uniform ANF-mediated inhibition by about 50% of the hepactic AHH activity was observed: in older animals the percentage became slightly higher. The investigation appears to confirm the change in cytochrome pattern,--especially as for the participation of cytochrome P-448,--according to the age and induction stimulus by 3-MC.