Depurination of 8-oxo-7,8-dihydroguanine (8-hydroxyguanine) nucleosides

Abstract

Data on the stability of N-glycosidic bonds were obtained and compared for 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-hydroxy-2′-deoxyguanosine; 8-oxo-dGuo), 8-oxo-7,8-dihydroguanosine (8-hydroxyguanosine; 8-oxo-Guo), and natural guanine nucleosides 2′-deoxyguanosine (dGuo) and guanosine (Guo). Cleavage of the N-glycosidic bond was induced by heat, γ-irradiation, or low pH. It was found that heat-induced hydrolysis of 8-oxo-dGuo proceeds with an activation energy of 117.3 kJ/mole (28 kcal/mole) and a rate constant of k = 6.4·-10 sec-1 at 37°C, pH 6.8. Depurination of 8-oxo-dGuo and 8-oxo-Guo by γ-radiation gave radiation-chemical yield (G-value) of 0.18 ± 0.01 and 0.08 ± 0.01 molecules per 100 eV, respectively. Acid-catalyzed hydrolysis (0.1 M HCl, 100°C) revealed that 8-hydroxy-derivatives of guanine nucleosides possess considerably more stable N-glycosidic bonds than those of natural nucleosides. Our results point to the unusually high stability of 8-hydroxyguanine nucleosides as compared to natural purine nucleosides. This form of guanine nucleoside damage apparently requires enzymatic repair.