title: Radiosensitization of DNA by Cisplatin Adducts Results from an Increase in the Rate Constant for the Reaction with Hydrated Electrons and Formation of Pt(I).
abstract: Pulse radiolysis measurements of the decay of hydrated electrons in solutions containing different concentrations of the oligonucleotide GTG with and without a cisplatin adduct show that the presence of a cisplatin moiety accelerates the reaction between hydrated electrons and the oligonucleotide. The rate constant of the reaction is found to be 2.23 × 10(10) mol(-1) L s(-1), which indicates that it is diffusion controlled. In addition, we show for the first time the formation of a Pt(I) intermediate as a result of the reaction of hydrated electrons with GTG-cisplatin. A putative reaction mechanism is proposed, which may form the basis of the radiosensitization of cancer cells in concomitant chemoradiation therapy with cisplatin.
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.affiliation: ‡Centre de cinétique rapide ELYSE, Laboratoire de chimie physique, Université de Paris-Sud 11, 91405, Orsay, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Marignier
authors.affiliation: ‡Centre de cinétique rapide ELYSE, Laboratoire de chimie physique, Université de Paris-Sud 11, 91405, Orsay, France.
authors.forename: M
authors.initials: M
authors.lastname: Mostafavi
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: J R
authors.initials: JR
authors.lastname: Wagner
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: D J
authors.initials: DJ
authors.lastname: Hunting
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: L
authors.initials: L
authors.lastname: Sanche
mesh_terms: D002945:Cisplatin / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D004583:Electrons; D006868:Hydrolysis; D007700:Kinetics; D011675:Pulse Radiolysis
chemical_list: D018736:DNA Adducts; D002945:Cisplatin