Aryl hydrocarbon hydroxylase and polycyclic hydrocarbon tumorigenesis: effect of the enzyme inhibitor 7,8-benzoflavone on tumorigenesis and macromolecule binding

Abstract

Aryl hydrocarbon hydroxylase is present and is inducible in mouse skin. 7,8-Benzoflavone, an inhibitor of the enzyme, markedly inhibits tumorigenesis by 7,12-dimethylbenz(a)anthracene, but has either no effect on or stimulates benzo(a)pyrene tumorigenesis. Thus, the role of aryl hydrocarbon hydroxylase appears highly specific for each polycyclic hydrocarbon, in respect to detoxification and/or activation of the hydrocarbon to a carcinogenic form. In parallel studies, we found that 7,8-benzoflavone significantly reduces the amount of 7,12-dimethylbenz(a)anthracene binding to mouse skin DNA, RNA, and protein, and the binding of benzo(a)pyrene to RNA and protein of mouse skin. 7,8-Benzoflavone exhibited a markedly lesser effect on the binding of benzo(a)pyrene to DNA.