Modification of DNA bases by photosensitized one-electron oxidation.
OBJECTIVE
To determine the distribution of base damage within isolated DNA upon oxidation by three type I photosensitizers in aerated aqueous solution.


METHODS
Aqueous solutions of DNA were exposed to UVA in the presence of riboflavin, benzophenone or menadione. Then, eight modified nucleobases were measured, using HPLC-EC, GC-MS or HPLC with fluorescence detection.


RESULTS
The three photosensitizers led to a predominant degradation of guanine bases within DNA. The relative yield of the three main guanine degradation products measured in DNA was similar with the three sensitizers. 8-OxodAdo was also produced in an almost constant yield with respect to its guanine analogue. The yield of oxidized pyrimidines was lower and was found to depend on the photosensitizer used. The results were compared with the yield of photosensitization-induced degradation of the 2'-deoxyribonucleosides.


CONCLUSIONS
The favoured photosensitized degradation of guanine within DNA may be explained by its lower oxidation potential with respect to that of the other bases, together with the occurrence of charge transfer through DNA. The base modification pattern determined in the present work is different from that obtained upon reaction of hydroxyl radicals. Under the latter conditions, pyrimidine oxidation products were generated more efficiently than by photosensitized one-electron oxidation.
Douki
T
T
Département de Recherche Fondamentale sur la Matière Condensée, CEA/Grenoble, France.
Cadet
J
J
D001577:Benzophenones / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000528:radiation effects*; D005720:Gamma Rays; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000378:metabolism; D010084:Oxidation-Reduction; D017319:Photosensitizing Agents / Q000494:pharmacology*; D012256:Riboflavin / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology
D001577:Benzophenones; D017319:Photosensitizing Agents; D014812:Vitamin K; D006147:Guanine; C047723:benzophenone; D004247:DNA; D012256:Riboflavin