title: DNA-polyamine cross-links generated upon one electron oxidation of DNA.
abstract: The possibility to induce the formation of covalent cross-links between polyamines and guanine following one electron oxidation of double stranded DNA has been evaluated. For such a purpose, a strategy has been developed to chemically synthesize the polyamine-C8-guanine adducts, and efforts have been made to characterize them. Then, an analytical method, based on HPLC separation coupled through electrospray ionization to tandem mass spectrometry, has been setup for their detection and quantification. Using such a sensitive approach, we have demonstrated that polyamine-C8-guanine adducts could be produced with significant yields in double stranded DNA following a one-electron oxidation reaction induced by photosensitization. These adducts, involving either putrescine, spermine, or spermidine, are generated by the nucleophilic addition of primary amino groups of polyamines onto the C8 position of the guanine radical cation. Our data demonstrate that such a nucleophilic addition of polyamines is much more efficient than the addition of a water molecule that leads to 8-oxo-7,8-dihydroguanine formation.
authors.affiliation: Laboratoire Lésions des Acides Nucléiques, Université Grenoble Alpes, INAC-SCIB, F-38000 Grenoble, France, CEA, INAC-SCIB, 17 rue des Martyrs, 38000 Grenoble cédex 9, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Silerme
authors.forename: Laure
authors.initials: L
authors.lastname: Bobyk
authors.forename: Marisa
authors.initials: M
authors.lastname: Taverna-Porro
authors.forename: Camille
authors.initials: C
authors.lastname: Cuier
authors.forename: Christine
authors.initials: C
authors.lastname: Saint-Pierre
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ravanat
mesh_terms: D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000302:isolation & purification; D004583:Electrons; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011073:Polyamines / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D003432:Cross-Linking Reagents; D011073:Polyamines; D004247:DNA; C427203:calf thymus DNA