Characterization of 5-methylchrysene-1,2-dihydrodiol-3,4-epoxide-DNA adducts

Products of reaction of the racemic anti bay region 1,2-dihydrodiol-3,4-epoxide of 5-methylchrysene with DNA were identified by comparison with the products formed in reactions with individual nucleotides. The latter products, i.e. two deoxyguanosine adducts and four deoxyadenosine adducts, were characterized by various spectroscopic methods. In DNA, in addition to the major deoxyguanosine adduct already identified by Melikian et al. (Cancer Res., 44, 2524, 1984), we have now identified a second deoxyguanosine adduct arising from the trans opening of the epoxide ring by the amino group of deoxyguanosine. This differs from the adduct characterized by Melikian et al. only in that it arises from the opposite enantiomer of the dihydrodiol epoxide. Three deoxyadenosine adducts were also found in DNA. Two of these arose from the trans opening of the epoxide ring of each dihydrodiol epoxide enantiomer by the amino group of deoxyadenosine and the third from the cis opening of the epoxide ring of one enantiomer. Approximately 32% of the racemic dihydrodiol epoxide reacts with DNA rather than with water and this high extent of reaction with DNA is attributed to the out-of-plane deformations arising from the methyl substitution in the bay region.