A comparison of the DNA intercalative binding of bay versus K region metabolites of benzo[a]pyrene

Abstract

The DNA intercalating properties of trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (1) and of trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene (2) have been compared in UV absorption and in fluorescence emission and fluorescence lifetime studies. Molecules 1 and 2 represent steric models of the two epoxide containing metabolites of benzo[a]pyrene, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and benzo[a]pyrene-4,5-oxide. The former of these metabolites is a highly carcinogenic bay region metabolite, the latter is a much less carcinogenic K region metabolite. The association constant for intercalation for model 1 is 5,226 M-1. This is more than 2.7 times greater than that for molecule 2. These results taken together with results form previous studies of bay and K region metabolite models of benz[a]anthracene suggest that intercalation is important to the overall carcinogenic activity of polycyclic aromatic hydrocarbons.