ENZYMATIC HYDROXYLATION OF BENZOPYRENE AND ITS RELATIONSHIP TO CYTOTOXICITY

Abstract

Aryl hydrocarbon hydroxylase, an inducible microsomal enzyme system, has been measured in cultures of normal and transformed hamster, mouse, and human cells. In order to determine the highest level of enzyme, the cells were induced by pretreatment with benz(a)anthracene. A correlation was found between the level of enzyme activity and the susceptibility of the cells to the cytotoxicity produced after treatment with benzopyrene. The results indicate that aryl hydrocarbon hydroxylase is the enzyme system responsible for cell susceptibility to the cytotoxic effect of benzopyrene and the toxic effect of benzopyrene is due to its enzymatic conversion to a cytotoxic metabolite. 3-Hydroxybenzopyrene, one of the products of the enzymatic hydroxylation of benzopyrene, was found to be cytotoxic to cells that were either susceptible or resistant to the cytotoxic effect of benzopyrene.