title: Hydrated electrons react with high specificity with cisplatin bound to single-stranded DNA.
abstract: Short oligonucleotides TTTTTGTGTTT and TTTTTTTGTTT in solution with and without cisplatin (cisPt) bound to the guanine bases were irradiated with γ-rays at doses varying from 0 to 2500 Gy. To determine the effect of hydrated electrons from water radiolysis on the oligonucleotides, we quenched (•)OH radicals with ethylenediaminetetraacetic acid (EDTA) and displaced oxygen, which reacts with hydrated electrons, by bubbling the solution with wet nitrogen. DNA strand breaks and platinum detachment were quantified by gel electrophoresis. Our results demonstrate that hydrated electrons react almost exclusively at the position of the cisPt adduct, where they induce cisPt detachment from one or both guanines in the oligonucleotide. Given the high yield of hydrated electrons in irradiated tissues, this reaction may be an important step in the mechanism of radiosensitization of DNA by cisPt.
authors.affiliation: Groupe en sciences des radiations, Faculté de médicine et des sciences de la santé, Université de Sherbrooke , Sherbrooke, Québec, Canada J1H 5N4.
authors.forename: B
authors.initials: B
authors.lastname: Behmand
authors.forename: P
authors.initials: P
authors.lastname: Cloutier
authors.forename: S
authors.initials: S
authors.lastname: Girouard
authors.forename: J R
authors.initials: JR
authors.lastname: Wagner
authors.forename: L
authors.initials: L
authors.lastname: Sanche
authors.forename: D J
authors.initials: DJ
authors.lastname: Hunting
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry*; D058645:Denaturing Gradient Gel Electrophoresis; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D005720:Gamma Rays
chemical_list: D000970:Antineoplastic Agents; D004277:DNA, Single-Stranded; D002945:Cisplatin