Abstract: | 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′ > C1′ > 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. |