| Abstract: | The hydrocarbon-deoxyribonucleoside adducts formed in mouse skin DNA have been determined following topical application of an initiating dose of benzo(a)pyrene to Swiss mice, a strain shown to be susceptible to benzo(a)pyrene-induced skin carcinogenesis. Several DNA-bound products were formed, of which the major one (60% of total adducts), in agreement with other workers' findings, was derived from reaction of (+/-) 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(alpha)pyrene (BDE) with the exocyclic aminogroup of deoxyguanosine. A further product (9-10% of total adducts), previously observed only after microsomal activation of benzo(a)pyrene, was observed and co-chromatographed with a further metabolite of 9-hydroxybenzo(alpha)pyrene bound to an uncharacterized base in the DNA. Two otherr products (2-3% of total adducts) were also found in the in vivo studies which co-chromatographed with BPDE-deoxyadenosine adducts and arose from cis and trans addition of the exocyclic amino group of deoxyadenosine to the 7R form, but not the 7S form, of BPDE. In contrast to this, the major in vitro deoxyadenosine-bound products, formed following reaction of BPDE with calf-thymus DNA, were derived from the 7S form of BPDE, suggesting either stereoselective formation or reaction of the 7R form of BPDE in mouse skin in vivo. Similar amounts of BPDE-deoxyguanosine and BPDE-deoxyadenosine adducts, as well as those derived from further metabolism of 9-hydroxybenzo(alpha)pyrene were formed in three strains of mice reported to have widely differing susceptibilities to polycyclic hydrocarbon-induced skin carcinogenesis. The relevance of these different hydrocarbon-DNA adducts to carcinogenesis requires further investigation. |
