8-Oxoguanine

Fig. 1 Schematic mechanism for the long-distance oxidation of DNA. Irradiation of the anthraquinone (AQ) and intersystem crossing (ISC) forms the triplet excited state (AQ 3), which is the species that accepts an electron from a DNA base (B) and leads to products. Electron transfer to the singlet excited state of the anthraquinone (AQ 1) leads only to back electron transfer. The anthraquinone radical anion (AQ ) formed in the electron transfer reaction is consumed by reaction with oxygen, which is reduced to superoxide. This process leaves a base radical cation (B+-, a hole ) in the DNA with no partner for annihilation, which provides time for it to hop through the DNA until it is trapped by water (usually at a GG step) to form a product, 7,8-dihydro-8-oxoguanine (8-OxoG)...

Fig. 4 Schematic representation of long-distance radical cation migration in DNA. In AQ-DNA(l), irradiation of the anthraquinone group linked at the 5 -terminus leads to reaction at GG steps that are 27 A and 44 A from the site of charge injection. The amount of reaction observed at each guanine is represented approximately by the length of the solid arrow. In UAQ-DNA(2), irradiation of the anthraquinone leads to reaction at each of the eight GG steps. However, replacement of a G by 7,8-dihydro-8-oxoguanine (8-OxoG) introduces a deep trap that inhibits reaction at guanines on the same side of the DNA as the trap...

Lynn et al. [71] demonstrated the damaging effect of arsenite on DNA. It has been shown that arsenite at low concentrations increased DNA oxidative damage in vascular smooth muscle cells (VSMCs) that can be a cause of arsenite-induced atherosclerosis. Bruskov et al. [72] found that heat induced the formation of 8-oxoguanine in DNA solution at pH 6.8, which was supposedly mediated by oxygen radicals. 

SWV was used for the investigation of charge transfer kinetics of dissolved zinc(II) ions [215-218] and uranyl-acetylacetone [219], cadmium(II)-NTA [220] and mthenium(III)-EDTA complexes [221], and the mechanisms of electrode reactions of bismuth(III) [222], europium(III) [223,224] and indium(III) ions [225], 8-oxoguanine [226] and selenium(IV) ions [227,228]. It was also used for the speciation of zinc(II) [229,230], cadmium(II) and lead(II) ions in various matrices [231-235]. 

The electrochemical processes of adsorption and oxidation of ds- and ssDNA on the GC electrode were discussed and studied by in situ FTIR [42]. It was also demonstrated that the well-known oxidation product 8-oxoguanine adsorbs strongly on the GC surface [29]. Adsorbed ssDNA can form a DNA layer which impedes the oxidation product diffusing away, blocking the GC surface [43,44]. 

Immunoassay kit, where the antibodies of 8-oxoguanine (96) are conjugated with fluorescein isothiocyante (97) as fluorophore and combine with the oxidized DNA. Detection of the greenish fluorescence is by fluorescence microscopy for tissues or by fluorescence-activated ceU sorting for cell suspensions . 

Damage to DNA by ROS may affect the thymine (43) residnes, as mentioned in Section IV.B.2 however, also guanine (160) residues of DNA are labile and may yield 8-oxoguanine (96). This fact is the basis of a qualitative in vitro immunoassay for DNA oxidative damage shown in Table 2 . ... 

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. 

Table 2 Deuterium isotope effect on the rate constants of the oxidation of guanine and 8-oxoguanine by 2-aminopurine neutral radicals in double-stranded DNA duplexes (adapted from [11] and [13]) ...

Le Page F, Randrianarison V, Marot D et al. BRCAl and BRCA2 are necessary for the transcription-coupled repair of the oxidative 8-oxoguanine lesion in human cells. Cancer Res 2000 60 5548-5552. 

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. 

Both NER and BER forms of excision repair remove a great variety of defects, many of which are a result of oxidative damage.657 720 Most prominent among these is 7,8-dihydro-8-oxoguanine (8-OG), which is able to base pair with either cytosine (with normal Watson-Crick hydrogen bonding) or with adenine, which will yield a purine-purine mismatch and aC G —> A T transversion mutation (Eq. 27-24), a frequent mutation in human cancers.721 722... 

Yermilov V, Rubio J, Ohshima H (1995) Formation of 8-nitroguanine in DNA treated with peroxyni-trite in vitro and its rapid removal from DNA by depurination. FEBS Lett 376 207-210 Yermilov V, Yoshie Y, Rubio J, Oshima H (1996) Effects of carbon dioxide/bicarbonate on induction of DNA single-strand breaks and formation of 8-nitroguanine, 8-oxoguanine and base-propenal mediated by peroxynitrite. FEBS Lett 399 67-70... 

Hickerson RP, Prat F, Muller CE, Foote CS, Burrows CJ (1999) Sequence and stacking dependence of 8-oxoguanine oxidation camparison of one-electron vs singlet oxygen mechanism. J Am Chem Soc 121 9423-9428... 

Wetmore SD, Boyd RJ, Erikson LA (1998b) Radiation products of thymine, 1-methylthymineand uracil investigated by Density Functional Theory. J Phys Chem B 102 5369-5377 White B, Smyth MR, Stuart JD, Rusling JF (2003) Oscillating formation of 8-oxoguanine during DNA oxidation. J Am Chem Soc 125 6604-6605... 

Prakash Rao PJ, Bothe E, Schulte-Frohlinde D (1992) Reaction of dithiothreitol and para-nitroace-tophenone with different radical precursors of OH radical-induced strand break formation of single-stranded DNA in anoxic aqueous solution. Int J Radiat Biol 61 577-591 Prat F, Houk KN, Foote CS (1998) Effect of guanine stacking on the oxidation of 8-oxoguanine in B-DNA. J Am Chem Soc 120 845-846... 

Sy D, Flouzat C, Eon S, Charlier M, Spotheim-Maurizot M (2001) Modelling radiation-induced damage in the lac operator-lac repressor complex. DNA damage 8-oxoguanine. Theor Chem Acc 106 137-145... 

OHP 528-529 8-oxoGua 424, 428 8-oxoguanine e211 /J-ODAP 536-537 02 reduction 911 Ochratoxin A 537, 688 Odour 756 Off... 

Following the increase in the height of the DNA bases oxidation peaks and/or searching for new electrochemical signals such as of 8-oxoguanine, Fig. 29.1, the interaction of DNA with different compounds is evaluated. 

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