Effect of 2'-Deoxyguanosine Oxidation at C8 Position on N-Glycosidic Bond Stability

Abstract

The influence of 2'-deoxyguanosine (dG) oxidation at the C-8 position on N-glycosidic bond stability was investigated. A kinetic analysis of dG and 8-oxo-2'-deoxyguanosine (8-oxodG) depurination reactions was carried out in water solutions at pH ranging from 2 to 7.4 and temperature of 100°C. The results indicate that N-glycosidic bond of 8-oxodG is significantly more stable in comparison with dG at any pH applied. At pH 5.1 hydrolysis rate of dG is 4.5-fold higher than that for 8-oxodG. The chemical stability of the modified nucleoside in oxidatively damaged DNA is one of important factors contributing to its mutagenic potential. Results of our experiments indicate that 8-oxodG, potentially mutagenic and carcinogenic nucleoside, is hardly susceptible to spontaneous depurination and its removal from cellular DNA depends mostly on the activity of DNA repair enzymes. © 1996, Verlag der Zeitschrift für Naturforschung. All rights reserved.