DNA Damage Emanating From a Neutral Purine Radical Reveals the Sequence Dependent Convergence of the Direct and Indirect Effects of γ-Radiolysis.

Nucleobase radicals are the major intermediates generated by the direct (e.g., dA) and indirect (e.g., dA•) effects of γ-radiolysis. dA• was independently generated in DNA for the first time. The dA/dA• equilibrium, and consequently the reactivity in DNA, is significantly shifted toward the radical cation by a flanking dA. Tandem lesions emanating from dA• are the major products when the reactive intermediate is flanked by a 5'-dGT. In contrast, when dA• is flanked by dA, the increased dA pK results in DNA damage arising from hole transfer. This is the first demonstration that sequence effects lead to the intersection of the direct and indirect effects of ionizing radiation.