Hole Migration is the Major Pathway Involved in Alkali-Labile Lesion Formation in DNA by the Direct Effect of Ionizing Radiation

Electron transfer via nucleobase hole migration has been extensively studied in recent years. Holes are produced in DNA via the direct effect of γ-radiolysis. However, the contribution of this pathway to DNA damage is difficult to discern because common products are formed via the direct and indirect (e.g., hydroxyl radical) pathways. A molecular probe ( 1 ) was designed that serves as a repository for holes in DNA. Upon one-electron oxidation, 1 fragments to fdU, which is an alkali-labile lesion. Incorporation of 1 in synthetic DNA enables one to determine the contribution of hole transfer to DNA damage by γ-radiolysis. We find that hole migration is the predominant pathway for alkali-labile lesion formation when DNA is exposed to 137 Cs in solution.