Hydroxyl radical-induced degradation of 2′-deoxyguanosine under reducing conditions

Abstract

Addition of hydroxyl radical to the base moiety of 2′-deoxyguanosine (dGuo) leads to the formation of two main radicals exhibiting oxidising and reducing properties, respectively. The oxidising radical reacts with oxygen to yield 2,2-diamino-5-[2-deoxy-β-D-erythro-pentofuranosyl)amino]oxazol-5(2H)-one (oxazolone) as the final product. The reducing radical is either preferentially oxidised into 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) or reduced into a 2,6-diamino-4-hydroxy-5-formamidopyrimidine derivative (FapydGuo) depending on conditions. We report here that the presence of reducing compounds (ascorbate or cysteine) strongly modifies the distribution of modified nucleosides upon γ irradiation of an aerated aqueous solution of dGuo. The yield of oxazolone decreases while that of 8-oxodGuo and FapydGuo increases. This was explained by the reduction of the oxidising radical which prevents the occurrence of the restitution of dGuo through a reaction between the oxidising and the reducing purine radicals. The study was extended to the decomposition of dGuo upon photochemical release of ˙OH by N-hydroxypyrimidine-2-thione (HPT). The analysis of the base modification products of dGuo induced by the latter system showed that HPT exhibits reducing properties and cannot be used as a pure photochemical source of ˙OH radical.