METABOLIC ACTIVATION OF BENZO(A)PYRENE AND BINDING TO DNA IN CULTURED HUMAN BRONCHUS

Abstract

Human bronchus is one target site for the carcinogenic action of tobacco smoke, which contains chemical carcinogens, including benzo(a)pyrene. Human bronchi were obtained from surgery or immediate autopsy and cultured in a chemically defined medium. The cultured bronchi were exposed to benzo(a)pyrene or its metabolites, and their levels of binding to DNA were measured. One of the benzo(a)pyrene metabolites, (-)-trans-7,8-diol, is more active in binding to DNA than benzo(a)pyrene and several of its metabolites, including (-)-trans-4,5-diol, (-)-trans-9,10-diol and phenols. The predominant metabolite formed by human bronchus from the (-)-trans-7,8-diol was found, by high pressure liquid chromatographic analysis, to be the diol epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. The results suggest that this diol epoxide is the major benzo(a)pyrene metabolite bound to DNA in human bronchus.