Studies on adduct formation of (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide with the oligonucleotides 5 '-d(CCTATCGTTATCC) and 5 '-d(CCTATm(5)CGTTATCC)

Adduct formation of (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide [B PDE] and 5'-d(CCTATCGTTATCC) or 5'-d(CCTATm(5)CGTTATCC) (G = binding target ) has been studied. The extent of trans-BPDE-N-2-dG adduct formation was hi gher in the oligonucleotide with 5'-d(m(5)CG) sequence context in both sing le- and double stranded form compared to the non-methylated analogue. The s timulating effect of m(5)dC on adduct formation has previously been demonst rated in other experimental systems. The increase in yield could possibly b e rationalized in terms of prestacking of the pyrenyl ring with the nucleob ases prior to the nucleophilic addition. In the present study, both UV abso rption and induced circular dichroism of the trans-BPDE-N-2-dG adduct in th e m(5)dC-containing duplex indicate substantial adduct heterogeneity and ar e consistent with the presence of both external localized complexes and tho se with intercalative binding characteristics.