Thymine oxidation potential

In general, reduction potentials of nucleobases have been studied much less than their oxidation potentials, and in particular water-based data are rather lacking [2, 35]. We therefore listed the available polarographic potentials measured in dimethylformamide and data obtained from pulse radiolysis studies or fluorescence quenching measurements. From the data in Table 1, it is evident that the pyrimidine bases are most easily reduced. The reduction potential of the T=T CPD lesion is close to the estimated value of the undamaged thymine base [34, 36]. 

As discussed earlier, guanine (G), adenine (A), cytosine (C), and thymine (T) in DNA can be modified by in vivo reactive species or different exogenous factors giving rise to a plethora of DNA base lesions. In vitro stndies with DNA or model componnds have shown that almost seventy different types of base lesions can be prodnced in DNA [55]. However, qnantification of all these lesions in cellular DNA is difficult. As a result, only abont 20 different base and sugar lesions have been identified so far in cells [56]. These include both simple and complex base lesions. Simple base lesions mainly consist of different oxidatively damaged products of DNA bases whereas complex base lesions mainly include bulky lesions like DNA-DNA and DNA-protein crosslinks. It should be noted that as the oxidation potential of G is the lowest among all the bases [57, 58], it is more freqnently attacked by different reactive species than others. Therefore, we will here mainly consider the formation of different simple base lesions related to the modifications of guanine in DNA by different in vivo reactive species. 

The major thymine family of lesions are the photodimers, of which the cis-syn cyclobutane photodimer (CPD) is the most abundant and most widely studied. The mechanism of formation of (CPD) (43) has been examined in both single- and double-stranded DNA, showing that dimerization occurs more readily in base paired states, presumably due to the formation of charge-transfer states. Pan and co-workers have also examined the effect of flanking purines on photodimerisation and showed that dimerization is strongly-dependent on the oxidation potential of the flanking purine, particularly at the 5 -thymine. ... 

Oxidative repair is not a unique feature of our Rh(III) complexes. We also demonstrated efficient long-range repair using a covalently tethered naphthalene diimide intercalator (li /0 1.9 V vs NHE) [151]. An intercalated ethidium derivative was ineffective at dimer repair, consistent with the fact that the reduction potential of Et is significantly below the potential of the dimer. Thymine dimer repair by a series of anthraquinone derivatives was also evaluated [151]. Despite the fact that the excited triplets are of sufficient potential to oxidize the thymine dimer ( 3 -/0 1.9 V vs NHE), the anthraquinone derivatives were unable to effect repair [152]. We attribute the lack of repair by these anthraquinone derivatives to their particularly short-lived singlet states anthraquinone derivatives that do not rapidly interconvert to the excited triplet state are indeed effective at thymine dimer repair [151]. These observations suggest that interaction of the dimer with the singlet state may be essential for repair. 

Deeble DJ, Schuchmann MN, Steenken S, von Sonntag C (1990) Direct evidence for the formation of thymine radical cations from the reaction of SO/" with thymine derivatives a pulse radiolysis study with optical and conductance detection. J Phys Chem 94 8186-8192 DeFelippis MR, Murthy CP, Faraggi M, Klapper MH (1989) Pulse radiolytic measurement of redox potentials the tyrosine and tryptophan radicals. Biochemistry 28 4847-4853 Delatour T, Douki T, D Ham C, Cadet J (1998) Photosensitization of thymine nucleobase by benzo-phenone through energy transfer, hydrogen abstraction and one-electron oxidation. J Photo-chem Photobiol 44 191-198... 

The electrochemical behaviour and the adsorption of nucleic acid molecules and DNA constituents have been extensively studied over recent decades [1-6]. Electrochemical studies demonstrated that all DNA bases can be electrochemically oxidized on carbon electrodes [7-13], following a pH-dependent mechanism. The purines, guanine (G) and adenine (A), are oxidized at much lower positive potentials than the pyrimidines, cytosine (C) and thymine (T), the oxidation of which occurs only at very high positive potentials near the potential corresponding to oxygen evolution, and consequently are more difficult to detect. Also, for the same concentrations, the oxidation currents observed for pyrimidine bases are much smaller than those observed for the purine bases. Consequently, the electrochemical detection of oxidative changes occurring in DNA has been based on the detection of purine base oxidation peaks or of the major... 

This figure, by Oliveira Brett and Matysik [80], showed for the first time that the pyrimidine bases thymine and csdosine can imdergo oxidation on glassy carbon electrodes albeit for very positive potentials and that the... 

DNA is also susceptible to free radical attack during oxidative stress. The participation of GST isoenzymes in the detoxification and repair of the potentially mutagenic radical damage to DNA has been studied by Ketterer and his colleagues. Both thymine hydroperoxides and DNA peroxidized by ionizing radiation in the presence of oxygen have been shown to serve as substrates for rat GST (T3, T4). However, these workers reported that the specificity of rat GST isoenzymes toward the peroxidized DNA differs from that toward the free thymine hydroperoxide, 5-hydroxymethyl uracil. From their data, Ketterer et al. (K7, K9) propose that GST act in concert with DNA glycosylase to repair oxidized DNA. 

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