8-oxo-guanine

Product analysis shows that the oxidative pathway of direct radiation damage to DNA results in a variety of products from each of the DNA bases [18] however, the dominant products are those from guanine such as 8-oxo-guanine and fapy-guanine as expected from the overall charge transport to guanine [18]. 

The insight provided by studying 8-oxo-guanine, and the ability to substitute DNA with a nucleobase that could be selectively oxidized by a low-potential complex, prompted us to search for other minimally substituted, redox-active nucleobases [92]. We therefore developed a library of nucleobases that were investigated using density functional theory (DFT) [93, 94] calculations self-consistently coupled to the conductorlike solvation model (COSMO) [95, 96]. The case of oxidation of nucleobases, particularly guanine. 

H. J. Helbocketal., DNA Oxidation Matters The HPLC-Electrochem-ical Detection Assay of 8-oxo-deoxyguanosine and 8-oxo-guanine, Proc. Natl. Acad. Sci. USA 95 (1998) 288-93. 

Similarly, oxidative damage can result from exposure to chemicals and cause small changes in DNA bases (e.g., formation of 8-oxodeoxyguanosine, 8-oxo-dG), which are potentially pro mutagenic (Fig. 6.41). 8-Oxo-guanine can be detected in urine. Exposure to some metals such as Cr (VII) and Ni (II) can cause the oxidation of bases and therefore potential mutations. 

Hydroxy-8-oxo-guanine (in general also with respect to dGuo, Guo and DNA)... 

David-Cordonnier M-H, Boiteux S, O Neill P (2001a) Efficiency of excision of 8-oxo-guanine within DNA clustered damage by XRS5 nuclear extracts and purified human OGGI protein. Biochemistry 40 11881-11818... 

Shukla LI, Adhikary A, Pazdro R, Sevilla MD (2004) Formation of 8-oxo-guanine radicals in y-irradi-ated DNA Evidence for multiple one-electron oxidations by long range hole transfer. Nucleic Acids Res 32 6565-6574... 

Another interesting topic, yet not well understood, is how the oxidation of nucleic acid bases influences the stability of DNA, and in particular, to what extent it changes the nature of intermolecular interactions. The biological consequences of damage to nucleic acids have been the subject of numerous experimental studies [39, 40], DNA may be exposed in vivo to hydroxyl radicals produced during endogenic cellular processes [41,42], Increased concentration of modified nucleic acid base derivatives (i.e., 8-oxo-guanine, 2-oxo-adenine) in cancer cells has been observed. For this reason, the analysis of the influence of modification of nucleic acid bases by hydroxyl radical on the nature of intermolecular interactions seems to be very advisable. The results of calculations presented in Fig. 20.2 show that... 

Damage due to hydroxyl radicals. Small amounts of reduced iron bound to our DNA may allow the Fenton reaction to occur, thus producing HO in the immediate vicinity of DNA. The HO radical attacks guanine (G) residues, producing residues of 8-oxo-guanine (oxo ),... 

Ij, X., Wright, P. M., and Lu, A. L. (2000). The C-terminal domain of MutY glycosylase determines the 7,8-dihydro-8-oxo-guanine specificity and is crucial for mutation avoidance, y BioL Chem. 275, 8448-8455. 

Holmberg RC, Tierney MT, Ropp PA, Berg EE, Grinstaff MW, Thorp HH (2003) Intramolecular electrocatalysis of 8-oxo-guanine oxidation secondary structure control of electron transfer in osmium-labeled oligonucleotides. Inorg Chem 42 6379-6387... 

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