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 then cultured in a chemically defined medium. The cultured bronchi were exposed to either benzo(a)pyrene or its metabolities, 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 is 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-tetrahy-drobenzo(a)pyrene. The results suggest that this diol-epoxide is the major benzo(a)pyrene metabolite bound to DNA in human bronchus.

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©1977 American Association for Cancer Research.