title: Direct radiation damage to crystalline DNA: what is the source of unaltered base release?
abstract: The radiation chemical yields of unaltered base release have been measured in three crystalline double-stranded DNA oligomers after X irradiation at 4 K. The yields of released bases are between 10 and 20% of the total free radical yields measured at 4 K. Using these numbers, we estimate that the yield of DNA strand breaks due to the direct effect is about 0.1 micromol J(-1). The damage responsible for base release is independent of the base type (C, G, A or T) and is not scavenged by anthracycline drugs intercalated in the DNA. For these reasons, reactions initiated by the hydroxyl radical have been ruled out as the source of base release. Since the intercalated anthracycline scavenges electrons and holes completely but does not inhibit base release, the possibility for damage transfer from the bases to the sugars can also be ruled out. The results are consistent with a model in which primary radical cations formed directly on the sugar-phosphate backbone react by two competing pathways: deprotonation, which localizes the damage on the sugar, and hole tunneling, which transfers the damage to the base stack. Quantitative estimates indicate that these two processes are approximately equally efficient.
authors.affiliation: Department of Biochemistry and Biophysics, University of Rochester, Rochester, New York 14642, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Razskazovskiy
authors.forename: M G
authors.initials: MG
authors.lastname: Debije
authors.forename: W A
authors.initials: WA
authors.lastname: Bernhard
mesh_terms: D020029:Base Pairing; D003460:Crystallization; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation
chemical_list: D004247:DNA