Metabolic activation of xenobiotic stilbene estrogens.

Abstract

Certain stilbene estrogens, in particular diethylstilbestrol, are established carcinogens in animals and in humans. The question is raised whether the formation of reactive metabolites is part of the carcinogenic mechanism of these compounds. Some aspects of the oxidative metabolism are briefly reviewed, with special emphasis on peroxidase-mediated metabolic activation. The interaction of the reactive intermediates with nucleic acids and proteins is described and examples of the induction of genetic damage in several short-term assays are given. From the available data it is concluded that metabolic activation may play a role in the process of neoplastic cell transformation induced by stilbene estrogens.