Involvement of the exocyclic amino group of deoxyguanosine in DNA-catalysed carcinogen detoxification.

The interactions of 7r,8t-dihydroxy-9t,10t-oxy-7,8,9,10-tetrahydrobenzo[a] pyrene (BPDE-I) with purified DNAs and synthetic polynucleotides of varying base composition have been studied. The ability of these polynucleotides to catalyse BPDE-I hydrolysis is strongly base-composition dependent, increasing with increasing (% G + C). Covalent binding of 3H-BPDE-I to DNA shows a similar, linear dependence on base composition. Association constants for non-covalent binding exhibit no clear base-composition dependence. Poly(dI-dC) is relatively ineffective in catalysing hydrolysis, suggesting that the exocyclic amino group of deoxyguanosine is involved in catalysis. Several plausible models for this dependence are presented, ranging from conformational changes with changing base composition to general acid catalysis by the exocyclic amino group of deoxyguanosine.