8-Oxoguanine, mutagenicity

The 8-oxoguanine mutagenicity causes loss of DNA base pairing specihcity [12-14], and has been the subject of intensive research becoming widely accepted as a biomarker of oxidative DNA damage and cellular oxidative stress [15, 16]. Oxidative stress in vivo is an imbalance between prooxidant and antioxidant reactions which causes disruption of the redox mechanisms. 

Simple experimental approaches to this problem recently started postulate that the repair of clustered DNA damage leads to conversion of nonlethal lesions, e.g., dihydrothymine, or mutagenic lesions, such as 8-OxoGuanine, into lethal double strand breaks. These early experiments have studied kinetics and influence of excision of base lesion within clustered DNA damage by E. coli and nuclear extracts [27,123-129]. 

Bruner SD, Norman DPG, Verdine GL. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature 403, 859-866, 2000. 

Another source of modified bases in both DNA and RNA is spontaneous or "accidental" alteration. Nucleic acids encounter many highly reactive and mutagenic materials including hydroxyl radicals, formed from 02, and are able to convert guanine rings into 7,8-dihydro-8-oxoguanine.362 Other reactive and carcinogenic compounds can form adducts with nucleic acid bases.363 See Eq. 5-18 and also Chapter 27. 

There are numerous other modifications of nucleobases possible, many of which are biologically relevant in that they lead to alternations in p/fa values, changes in tautomer structure as well as their base pairing patterns (55). Examples include ligands such as N6-methoxyadenine, which is a promutagen (66, 67) as well as 8-oxoadenine and 8-oxoguanine (68), which are known mutagens. 

A.K. Singh et al., Mismatch base pairing of the mutagen 8-oxoguanine and its derivatives with adenine A theoretical search for possible antimutagenic agents. Int. J. Quantum Chem. 102, 343-351 (2005)... 

Mishra PC, Singh AK, Suhai S (2005) Interaction of singlet oxygen and superoxide radical anion with guanine and formation of its mutagenic modification 8-oxoguanine. Int J Quant Chem 102 282-301... 

One pathway for the formation of 8-oxoguanine, a mutagenic derivative of gna-nine, involves the oxidation of this base by one electron, followed by the reaction of the guanine radical cation with water or O2. The presence of 8-oxo-G can be... 

In a study by Kuwahara et al. (2004), the effect of canolol on peroxynitrite-medi-ated mutagenicity in bacteria was analysed. In DNA, purine nucleotides are vulnerable to oxidation and to adduct formation by peroxynitrite, whereby 8-oxoguanine and 8-nitroguanine are two of the major products (Salgo et al., 1995 Szab6 and Ohshima, 1997 Burney et al., 1999 Niles et al., 2006). Moreover, peroxynitrite can cause deoxyribose oxidation and DNA strand breaks (Kennedy et al., 1997). 

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