DNA tandem lesions containing 8-oxo-7,8-dihydroguanine and formamido residues arise from intramolecular addition of thymine peroxyl radical to guanine.
Exposure of aerated aqueous solutions of dinucleoside monophosphates bearing both a pyrimidine base and a guanine residue to ionizing radiation leads to the formation of 8-oxo-7,8-dihydroguanine/formamido tandem lesions (8-oxodG/dF). Recent evidence for the formation of the latter damage within isolated DNA emphasized the possible biological relevance of this class of lesions. Therefore, an extensive mechanistic study of the formation of 8-oxodG/dF was carried out with thymine and guanine containing dinucleoside monophosphates (dGpdT and dTpdG). First, the peroxyl radical-induced degradation of guanine within dGpdT and dTpdG was studied in order to assess the possibility of intramolecular electron transfer between guanine and thymine peroxyl radicals. Then, the formation of a series of tandem lesions involving a formamido residue, thymine glycols, 8-oxodG, and oxazolone was monitored within aerated aqueous solutions of dTpdG and dGpdT exposed to gamma-radiation. The absence of formation of tandem lesions other than 8-oxodG/dF in significant yield led to us propose a new mechanism involving addition of the thymine peroxyl radical to the guanine moiety. This received support from (18)O labeling experiments.
Douki
Thierry
T
DRFMC, Service de Chimie Inorganique et Biologique, Laboratoire des Lésions des Acides Nucléiques, CEA/Grenoble, 17, Avenue des Martyrs, F-38054 Grenoble Cedex 9, France. tdouki@cea.fr
Rivière
Johann
J
Cadet
Jean
J
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry*; D015226:Dinucleoside Phosphates / Q000737:chemistry* / Q000528:radiation effects; D006147:Guanine / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010103:Oxygen Isotopes; D010545:Peroxides / Q000737:chemistry; D013941:Thymine / Q000737:chemistry
D015226:Dinucleoside Phosphates; D010103:Oxygen Isotopes; D010545:Peroxides; C049375:perhydroxyl radical; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D013941:Thymine