Contribution of One‐Electron Oxidation of Purine and Pyrimidine Bases to the Photo‐ and Radiation‐Induced Damage to Cellular DNA

One‐electron oxidants that include type I photosensitizers, biologically relevant carbonate anion radical generators, and high intensity UVC nanosecond lasers are able to ionize in aqueous solution purine and pyrimidine nucleobases. The survey is aimed at critically reviewing the available information on the fate of initially generated base radical cations that essentially involve deprotonation and nucleophilic addition reactions. Accumulated evidence leads to the conclusion that one‐electron oxidation reactions of nucleobases partly mimic the oxidizing features of hydroxyl radical, the main biologically relevant oxidant, in terms of formed degradation products. In contrast to the relatively nonspecific attack of hydroxyl radicals, guanine sites are the main targets of one‐electron oxidation. This may be rationalized by efficient redistribution of base radical cations through charge transfer along double‐stranded DNA with preferential final product formation at guanines, as illustrated by the overwhelming formation of 8‐oxo‐7,8‐dihydroguanine. Interestingly, a similar observation was made for cellular DNA; thus, providing strong support for the occurrence of hole migration in model DNA substrates as well as in cells. The specific distribution of DNA degradation products displayed by one‐electron oxidants was used to provide further support for the modest role of direct effects of ionizing radiation in the oxidative degradation of cellular DNA.