Efficacy and site specificity of hydrogen abstraction from DNA 2-deoxyribose by carbonate radicals.
The carbonate radical anion CO(3)(•-) is a potent reactive oxygen species (ROS) produced in vivo through enzymatic one-electron oxidation of bicarbonate or, mostly, via the reaction of CO(2) with peroxynitrite. Due to the vitally essential role of the carbon dioxide/bicarbonate buffer system in regulation of physiological pH, CO(3)(•-) is arguably one of the most important ROS in biological systems. So far, the studies of reactions of CO(3)(•-) with DNA have been focused on the pathways initiated by oxidation of guanines in DNA. In this study, low-molecular products of attack of CO(3)(•-) 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' > C1' > C5' for both CO(3)(•-) and the hydroxyl radical, though the relative contribution of the C1' damage induced by CO(3)(•-) 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 CO(3)(•-) primarily as a one-electron oxidant with fairly low reactivity toward the sugar-phosphate backbone.
a Department of Chemistry , East Tennessee State University , Johnson City , USA.
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M
Roginskaya
a Department of Chemistry , East Tennessee State University , Johnson City , USA.
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TJ
Moore
a Department of Chemistry , East Tennessee State University , Johnson City , USA.
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D
Ampadu-Boateng
b Department of Physics and Astronomy , East Tennessee State University , Johnson City , USA.
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Y
Razskazovskiy
D000818:Animals; D002254:Carbonates / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage / Q000502:physiology*; D003855:Deoxyribose / Q000737:chemistry; D005609:Free Radicals / Q000633:toxicity*; D006859:Hydrogen / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012474:Salmon
D002254:Carbonates; D005609:Free Radicals; D017382:Reactive Oxygen Species; D003855:Deoxyribose; D006859:Hydrogen; D004247:DNA
2-deoxyribose; DNA; carbonate radical; hydrogen abstraction; oxidative damage