title: Oxidation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by oxyl radicals produced by photolysis of azo compounds.
abstract: Oxidative damage to 8-oxo-7,8-dihydroguanine (8-oxoG) bases initiated by photolysis of the water-soluble radical generator 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) has been investigated by laser kinetic spectroscopy. In neutral oxygenated aqueous solutions, 355 nm photolysis of AAPH initiates efficient one-electron oxidation of the 8-oxodG nucleosides directly monitored by the appearance of the 8-oxodG(*+)/8-oxodG(-H)* radicals at 325 nm. The reaction kinetics consist of a mechanism that includes the transformation of the 2-amidinoprop-2-peroxyl radicals (ROO*) derived from photolysis of AAPH to more reactive 2-amidinoprop-2-oxyl radicals (RO*), which directly react with the 8-oxoG bases. The major pathways for the formation of end products of 8-oxoG oxidation include the combination of the 8-oxodG(*+)/8-oxodG(-H)* radicals with superoxide (O(2)(*-)) and ROO* radicals in approximately 1:1 ratios, as demonstrated by experiments with Cu,Zn superoxide dismutase, to form dehydroguanidinohydantoin (Gh(ox)) derivatives. This mechanism was confirmed by analysis of the end products produced by the oxidation of two substrates: (1) the 8-oxoG derivative 2',3',5'-tri-O-acetyl-7,8-dihydroguanosine (tri-O-Ac-8-oxoG) and (2) the 5'-d(CCATC[8-oxoG]CTACC) sequence. The major products isolated by HPLC and identified by mass spectrometry methods were the tri-O-Ac-Gh(ox) and 5'-d(CCATC[Gh(ox)]CTACC products.
authors.affiliation: Chemistry Department, New York University, New York, New York 10003-5180, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Shao
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Geacintov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Shafirovich
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000578:Amidines / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D007834:Lasers; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry* / Q000633:toxicity; D010782:Photolysis
chemical_list: D000578:Amidines; D010545:Peroxides; C049375:perhydroxyl radical; C046728:2,2'-azobis(2-amidinopropane); D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
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