Effect of 2'-deoxyguanosine oxidation at C8 position on N-glycosidic bond stability.
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 degrees 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.
Bialkowski
K
K
Department of Clinical Biochemistry, University School of Medical Sciences, Bydgoszcz, Poland.
Cysewski
P
P
Olinski
R
R
D003849:Deoxyguanosine / Q000737:chemistry*; D004355:Drug Stability; D006027:Glycosides; D006358:Hot Temperature; D006868:Hydrolysis; D007700:Kinetics; D015394:Molecular Structure; D010084:Oxidation-Reduction
D006027:Glycosides; D003849:Deoxyguanosine