Deoxyribose Oxidation

2 -deoxyribose oxidation products, in general, contribute to complex DNA lesions caused by ionizing radiation and OH radicals, with closely opposed strand breaks and oxidized abasic sites [151, 152]. The chemical biology of 2 -deoxyribose oxidation has been reviewed recently [153], so this portion of the chapter on RNS and DNA damage will only survey the product spectrum. 

Its chemical analogy to the physiologically important lysine N-acetylation suggests that lysine N-formylation may interfere with signaling mediated by histone modifications. 

---

Oxidation of the 2 -position is perhaps the least-studied 2 -deoxyribose oxidation chemistry and results in the formation of a D-erythrose abasic site (Figure 2.4) [163, 164]. With implications for the biological response to 2 -deoxyribose oxidation, this abasic site is substantially more stable to hydrolysis than the native and other oxidized abasic sites, with a half-life of 3h in 0.1 M NaOH at 37°C [165],... 

Variation of 2 -Deoxyribose Oxidation Chemistry as a Function of the Oxidant... 

Hydroxyl Radical-Mediated 2-Deoxyribose Oxidation Reactions 67... 

Gosule LC, Schellman JA (1976) Compact form of DNA induced by spermidine. Nature 259 333-335 GoyneTE, Sigman DS (1987) Nuclease activity of 1,10-phenanthroline-copper ion. Chemistry of deoxyribose oxidation. J Am Chem Soc 109 2846-2848... 

Another hypothesis was recently proposed by Afanas ev [63] to explain the inability of various OH scavengers to prevent deoxyribose oxidation by xanthine oxidase in the absence of iron-chelating EDTA. His hypothesis is that ferrous peroxy complexes, Fe(OOH)+, may be transiently formed, to decompose into two different reactive species, FeO+ and OH, which should both be very strong free radical initiators. There is no experimental data to support this speculation however. 

Awada, M. and Dedon, P.C. (2001) Formation of the l.N -glyoxal adduct of deoxyguanosine by phosphoglycolalde-hyde, a product of 3 -deoxyribose oxidation in DNA. Chem. Res. Toxicol., 14,1247-1253. 

Two other deoxyribose oxidation pathways were only observed by Oyushi and Sugiyama in addition to Cl and C4 oxidations previously described, during LC/ESI-MS analysis of the oxidation products of a hexanucleotide duplex produced by Cu(phen)2 in the presence of mercaptopropionic acid and air (23). 

In order to detect nucleobase oxidation if any, a heating step in piperidine 1 M was also performed, but no clear evolution of the cleavage patterns was observed in accordance to systems realizing probably preferentially deoxyribose oxidation. 

The product of deoxyribose oxidation at Cl, 5, could be observed by HPLC. However, it was noted that a minor amount of C4 hydroxylation may be observed as well at some residues in the loops. The oxidation of the C4 -H bond of some deoxyribose units in the single-stranded loops was due to an hydroxylation (formation of 4 -hydroxylated abasic site, 23), no 3 -phosphogly-colate were detected. The C4 oxidation mechanism was evidenced, on polyacrylamide gels, by the protection of NaBH4 toward piperidine sensitive cleavage at some T residues. 

In the case of copper complexes, the chemistry is less well understood. High valent copper-oxo species are not likely to be formed, consequently copper-hydroperoxo or copper-hydroxo species are usually proposed as active species in DNA oxidation. These species are thus more susceptible to homo-lytic cleavage of the peroxide or the metal-hydroxo bond and consequently, to 1-electron oxidation mechanism. However, the labeling of the product of deoxyribose oxidation at Cl by Cu(l,10-phenanthroline)2 clearly demonstrated that these complexes can mediate a 2-electron oxidation mechanism of DNA damage since the oxygen atom incorporated in DNA originates from H2O. 

Primary event may be deoxyribose oxidation, followed by base release. Addition of reductant (see other listings in No. 4, and [85T4]) or H2O2 [85T4] may increase rate. 

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). 

---