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Oxidised guanidinohydantoin (Ghox) and spiroiminodihydantoin (Sp) are major products of iron- and copper-mediated 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2-deoxyguanosine oxidation

White, Blánaid orcid logoORCID: 0000-0003-2982-8752, Tarun, Maricar C., Gathergood, Nicholas, Rusling, James F. and Smyth, Malcolm R. (2005) Oxidised guanidinohydantoin (Ghox) and spiroiminodihydantoin (Sp) are major products of iron- and copper-mediated 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2-deoxyguanosine oxidation. Molecular BioSystems, 2005 (1). pp. 373-381. ISSN 1742-206X

Abstract
8-Oxo-7,8-dihydroguanine (8-oxoGua), an important biomarker of DNA damage in oxidatively generated stress, is highly reactive towards further oxidation. Much work has been carried out to investigate the oxidation products of 8-oxoGua by one-electron oxidants, singlet oxygen, and peroxynitrite. This report details for the first time, the iron- and copper-mediated Fenton oxidation of 8-oxoGua and 8-oxo-7,8-dihydro-29-deoxyguanosine (8-oxodGuo). Oxidised guanidinohydantoin (Ghox) was detected as the major product of oxidation of 8-oxoGua with iron or copper and hydrogen peroxide, both at pH 7 and pH 11. Oxaluric acid was identified as a final product of 8-oxoGua oxidation. 8-oxodGuo was subjected to oxidation under the same conditions as 8-oxoGua. However, dGhox was not generated. Instead, spiroiminodihydantoin (Sp) was detected as the major product for both iron and copper mediated oxidation at pH 7. It was proposed that the oxidation of 8-oxoGua was initiated by its one-electron oxidation by the metal species, which leads to the reactive intermediate 8-oxoGua?+, which readily undergoes further oxidation. The product of 8-oxoGua and 8-oxodGuo oxidation was determined by the 29-deoxyribose moiety of the 8-oxodGuo, not whether copper or iron was the metal involved in the oxidation.
Metadata
Item Type:Article (Published)
Refereed:Yes
Subjects:Physical Sciences > Organic chemistry
Physical Sciences > Chemistry
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Chemical Sciences
Research Institutes and Centres > National Centre for Sensor Research (NCSR)
Publisher:RSC Publishing
Official URL:http://dx.doi.org/10.1039/b511756a
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 License. View License
ID Code:1
Deposited On:25 Oct 2006 by DORAS Administrator . Last Modified 07 Jan 2019 10:23
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