Direct radiation damage to crystalline DNA : what is the source of unaltered base release?

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 µmol 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

The yield of strand breaks resulting from direct-type effects in crystalline DNA x-irradiated at 4 K and room temperature

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Efficacy and Site Specificity of Hydrogen Abstraction From DNA 2-Deoxyribose by Carbonate Radicals

The carbonate radical anion CO3•- is a potent reactive oxygen species (ROS) produced in vivo through enzymatic one-electron oxidation of bicarbonate or, mostly, via the reaction of CO2 with peroxynitrite. Due to the vitally essential role of the carbon dioxide/bicarbonate buffer system in regulation of physiological pH, CO3•- is arguably one of the most important ROS in biological systems. So far, the studies of reactions of CO3•- with DNA have been focused on the pathways initiated by oxidation of guanines in DNA. In this study, low-molecular products of attack of CO3•- on the sugar-phosphate backbone in vitro were analyzed by reversed phase HPLC. The selectivity of damage in double-stranded DNA (dsDNA) was found to follow the same pattern C4′ \u3e C1′ \u3e C5′ for both CO3•- and the hydroxyl radical, though the relative contribution of the C1′ damage induced by CO3•- is substantially higher. In single-stranded DNA (ssDNA) oxidation at C1′ by CO3•- prevails over all other sugar damages. An approximately 2000-fold preference for 8-oxoguanine (8oxoG) formation over sugar damage found in our study identifies CO3•- primarily as a one-electron oxidant with fairly low reactivity toward the sugar-phosphate backbone

Strand breaks in x-irradiated crystalline DNA : alternating CG-oligomers

Direct ionization of crystalline d(CGCGCGCG) and d(CGCGCGCGCG) oligomers produces 3'- and 5'-phosphate-terminated fragments as the main strand breakage products detectable by ion-exchange chromatography. The nature of the base has no effect on the probability of strand breakage at the given site. The yields of 3'-phosphates are systematically lower than the yields of the 5'-phosphates originating from the same cleavage site, pointing to the possible presence of unidentified products with sugar remnants attached to the 3'-end. These results show that direct ionization is efficient at producing single-strand breaks in DNA and its action is relatively indiscriminate with respect to base sequence