Comparative Analysis of Four Oxidized Guanine Lesions from Reactions of DNA with Peroxynitrite, Singlet Oxygen, and γ-Radiation
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Cui_2013-Comparative analysis of four.pdf
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Author(s)
Cui, Liang
Ye, Wenjie
Wishnok, John S.
Taghizadeh, Koli
Dedon, Peter C.
Prestwich, Erin
Tannenbaum, Steven Robert
Date Issued
November 2012
Journal
Chemical Research in Toxicology
Publisher
American Chemical Society (ACS)
Citation
Cui, Liang, Wenjie Ye, Erin G. Prestwich, John S. Wishnok, Koli Taghizadeh, Peter C. Dedon, and Steven R. Tannenbaum. “Comparative Analysis of Four Oxidized Guanine Lesions from Reactions of DNA with Peroxynitrite, Singlet Oxygen, and γ-Radiation.” Chemical Research in Toxicology 26, no. 2 (February 18, 2013): 195-202. © 2012 American Chemical Society
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Final published version
Abstract
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–response 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.
MIT Department
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1021/tx300294d
