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

Addition of hydroxyl radical to the base moiety of 2'-deoxyguanosine (dGuo) leads to the formation of two main radicals exhibiting oxidising and reduc ing properties, respectively. The oxidising radical reacts with oxygen to y ield 2,2-diamino-5-[2-deoxy-beta-D-erythro-pentofuranosyl)amino]oxazol-5(2H )-one (oxazolone) as the final product. The reducing radical is either pref erentially oxidised into 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) or reduced into a 2,6-diamino-4-hydroxy-5-formamidopyrimidine derivative (Fap ydGuo) depending on conditions. We report here that the presence of reducin g compounds (ascorbate or cysteine) strongly modifies the distribution of m odified nucleosides upon gamma irradiation of an aerated aqueous solution o f dGuo. The yield of oxazolone decreases while that of 8-oxodGuo and FapydG uo 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 exte nded to the decomposition of dGuo upon photochemical release of (OH)-O-. by N-hydroxypyrimidine-2-thione (HPT). The analysis of the base modification products of dGuo induced by the latter system showed that HPT exhibits redu cing properties and cannot be used as a pure photochemical source of (OH)-O -. radical.