Structures of Covalent Nucleoside Adducts Formed from Adenine, Guanine, and Cytosine Bases of DNA and the Optically Active Bay-Region 3,4-Diol 1,2-Epoxides of Benzanthracene

Article abstract of DOI:10.1021/jo00067a039

Chemical structures of the principal covalent adducts formed from DNA upon reaction in vitro with the four optically active 3,4-diol 1,2-epoxides of benzanthracene have been elucidated at the nucleoside level.In addition to adducts formed by cis and trans addition of the exocyclic amino groups of deoxyadenosine (dA) and deoxyguanosine (dG) and a trans deoxycytidine (dC) adduct, chemical characterization of a deglycosylated N-7 dG adduct formed in DNA by trans opening of the (4S,3R)-diol (2R,1S)-epoxide isomer is reported.Relative stereochemistries of the adducts (cis versus trans opening of the epoxides by the exocyclic amino groups) were deduced from the coupling constants of the methine protons of the tetrahydro benzo rings of the acetylated derivatives.Adducts having (S)-configuration at the attachment site on the hydrocarbon moiety have CD spectra that exhibit a positive band at 250-260 nm and a negative band at longer wavelengths, whereas (R)-configuration at this center gives rise to CD spectra with bands of approximately equal intensity and opposite sign.This allowed assignment of cis versus trans addition to the chiral epoxides for adducts that were not generated in sufficient quantity to obtain NMR spectra.Analysis of the patterns of adducts derived from benzanthracene, benzophenanthrene, and benzopyrene shows that the comparative tumorigenicities of the diol epoxide isomers of each hydrocarbon do not correlate well with the extent of adduct formation, the ratio of cis versus trans addition to the epoxide, the propensity for forming adducts at dC or the N-7 position of dG, or the ratio of adduct formation at dA versus dG, although tumorigenicity may correlate with the ability to form dG adducts with (S)-configuration at the N-substituted benzylic carbon, especially those arising from trans addition to the epoxide.