Oxidation of 8-Oxo-7,8-dihydro-2′-deoxyguanosine by Oxyl Radicals Produced by Photolysis of Azo Compounds

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• 作者：Jie Shao ; Nicholas E. Geacintov ; Vladimir Shafirovich
• 刊名：Chemical Research in Toxicology
• 出版年：2010
• 出版时间：May 17, 2010
• 年：2010
• 卷：23
• 期：5
• 页码：933-938
• 全文大小：207K
• 年卷期：v.23,no.5(May 17, 2010)
• ISSN：1520-5010

文摘

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 (O₂^•−) 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.