Modulation of Rat Hepatic Aryl Hydrocarbon Hydroxylase by Various Flavones and Polycyclic Aromatic Hydrocarbons

Publisher Website
Google Scholar
Abstract
The microsomal cytochrome P-450-dependent aryl hydrocarbon hydroxylase is important in the detoxification of polycyclic hydrocarbons as well as their activation to cytotoxic or carcinogenic derivatives. We have studied compounds that can modify the activity of this enzyme system. Three types of flavones ae distinguished on the basis of their effect on the constitutive and polycyclic hydrocarbon-induced rat hepatic enzyme activity: (a) the 5,6- and 7,8-benzoflavones and their more hydrophobic derivatives inhibit the induced enzyme and increase or do not affect the constitutive enzyme activity; (b) derivatives typified by the 4''-hydroxylated benzoflavones similarly decrease both induced and constitutive activities; (c) polyhydroxyflavones inhibits the constitutive enzyme more than the induced enzyme. Two polycyclic hydrocarbons, 9-chloro-7H-dibenzo(a,g)carbazole and 6-aminochrysene, both potent inhbitors of the enzyme system, affect the constitutive and induced enzyme similar to compounds in groups a and b, respectively. The various activity-modulating compounds are useful reagents for distinguishing closely related enzymes present in a variety of different tissues and species under different conditions.