Comparative Analysis of Four Oxidized Guanine Lesions from Reactions of DNA with Peroxynitrite, Singlet Oxygen, and 纬-Radiation

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• 作者：Liang Cui ; Wenjie Ye ; Erin G. Prestwich ; John S. Wishnok ; Koli Taghizadeh ; Peter C. Dedon ; Steven R. Tannenbaum
• 刊名：Chemical Research in Toxicology
• 出版年：2013
• 出版时间：February 18, 2013
• 年：2013
• 卷：26
• 期：2
• 页码：195-202
• 全文大小：336K
• 年卷期：v.26,no.2(February 18, 2013)
• ISSN：1520-5010

文摘

Oxidative damage to DNA has many origins, including irradiation, inflammation, and oxidative stress, but the chemistries are not the same. The most oxidizable base in DNA is 2-deoxyguanosine (dG), and the primary oxidation products are 8-oxodG and 2-amino-imidazolone. The latter rapidly converts to 2,2-diamino-oxazolone (Ox), and 8-oxodG is further oxidized to spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh). In this study, we have examined the dose鈥搑esponse relationship for the formation of the above four products arising in calf thymus DNA exposed to gamma irradiation, photoactivated rose bengal, and two sources of peroxynitrite. In order to carry out these experiments, we developed a chromatographic system and synthesized isotopomeric internal standards to enable accurate and precise analysis based upon selected reaction monitoring mass spectrometry. 8-OxodG was the most abundant products in all cases, but its accumulation was highly dependent on the nature of the oxidizing agent and the subsequent conversion to Sp and Gh. Among the other oxidation products, Ox was the most abundant, and Sp was formed in significantly greater yield than Gh.