Thermal destabilization of DNA oligonucleotide duplexes by exocyclic adducts on adenine or cytosine depends on both the base and the size of adduct

Numerous carcinogens or their bifunctional metabolites modify DNA bases by forming additional exocyclic rings on the base moiety. These modifications form exocyclic rings between N1 and N6 of dA, N3 and N4 of dC or N1 and N2 of dG, as well as the N2 and N3 of dG. This study focuses on the reaction products of dA and dC with chloroacetaldehyde, bis-chloroethyl nitrosourea and para-benzoquinone, which form etheno, ethano and para-benzoquinone derivatives, respectively. The three dC adducts and three dA adducts were each incorporated site-specifically into 25-nucleotide-long deoxyoligonucleotides. All duplexes with a single modified dA or dC adduct opposite the normal complement showed decreased thermal stability, as compared with the unmodified control duplex. The destabilizations ranges from -2 degrees C to -13 degrees C, depending on saturation, the size of the adduct and the nature of the base. Energy-minimized molecular models of the duplexes illustrate various degrees of distortions by the adducts, the para-benzoquinone adducts showing the greatest distortion.