DNA adducts from syn 7-methylbenz[a]anthracene 3,4-dihydrodiol 1,2-epoxide

DNA adducts derived from reaction of the racemic bay region syn 7-methylben z[a]anthracene 3,4-dihydrodiol 1,2-epoxide with calf thymus DNA in vitro we re tentatively identified. Eight markers (four deoxyguanosine and four deox yadenosine adducts) were obtained from separate reactions of the racemic sy n dihydrodiol epoxide with deoxyguanylic and deoxyadenylic acids. The nucle oside of origin of individual DNA products was established by comparing HPL C retention times and UV spectra of DNA adducts with those of the adduct ma rkers. All DNA adducts eluted with retention times and had UV spectra that corresponded to the purine nucleoside adducts. Circular dichroism spectra o f the marker adducts allowed assignment of S and R configuration at C-1, th e site of attachment of the hydrocarbon residue to the nucleoside. The CD s pectra were comprised of four pairs of spectra that were mirror images of o ne another. Each pair consisted of the two cis or two trans products result ing from epoxide ring opening of each dihydrodiol epoxide enantiomer by the exocyclic amino group of the deoxyguanosine or deoxyadenosine residues. Si nce the adducts obtained were insufficient for NMR studies, assignment of c is and trans structures was made by comparison of elution sequence and circ ular dichroism data with those of the known syn benz[a]anthracene dihydrodi ol epoxide adducts. The ratio of dGuo/dAdo adducts in DNA was 1.5, close to the ratio reported for syn benz[a]anthracene dihydrodiol epoxide. DNA addu cts accounted for 27% of the original dihydrodiol epoxide used. The ratios of dGuo/dAdo modifications were 58/42 and 69/31 for the 3S,4R-dihydrodiol 1 S,2R-epoxide and the 3R,4S-dihydrodiol 1R,2S-epoxide enantiomers, respectiv ely. Approximately 75% of total DNA adducts was derived from the 3S,4R-dihy drodiol 1S,2R-epoxide enantiomer and these were largely cis adducts.