Products Derived from the Guanine Moiety

The products derived from G that have been detected in free-radical damaged DNA are depicted in Fig. 12.10. 

The product yields in y-irradiated DNA are given in Tables 12.5-12.7. FAPY-G has always been observed, but 8-oxo-G yields were extremely low, when y-ir-radiations were carried out under N2. This may serve as a caveat for the common practice to use 8-oxo-G as a kind of marker for free-radical DNA damage (for assays see Chap. 13.2). Besides the other products reported in Table 12.5, 8 cG lesions per 106 bases are formed per Gy in y-irradiated N20-saturated DNA (50 pg ml-1) solution (Dizdaroglu et al. 2001a corresponding to 1.6 x 10 9 mol J-1), and this lesion has also been observed in y-irradiated cultured human cells (Dizdaroglu 1986 for its elimination by nucleotide excision repair see Kuraoka et al. 2000). 

As with other reducing agents, G reacts with 02 (Chap. 10.2) which is the most abundant freely diffusing peroxyl radical. Upon two-photon excitation of a 2-aminopurine-containing ss- and dsODN in air-saturated solutions, photoionization leads to the formation of eaq (and subsequently 02 ) and the 2-amino-purine radical cation oxidizes a neighboring G (leading to G plus H+ Misiaszek et al. 2004). G and 02 react with one another (ssDNA k = 4.1 x 108 dm3 mol-1 s 1 dsDNA 2.7 x 108 dm3 mol-1 sH). In the majority of these events G is reformed, but with an efficiency of 15% Iz and, to a minor extent, 8-oxo-G are formed. The suggested mechanism is shown in Chapter 10.2. 

In the reactions of peroxynitrite, C03 plays a major role (Chap. 2.2). In the self-complementary ODN d(AACGCGAATTCGCGTT) it reacts (k= 1.9 x 109 dm3 mol-1 s 1) exclusively with G (by ET) inducing an alkali-labile lesion (Shafirov-ich et al. 2004). When NO and 02 is generated simultaneously as precursors of peroxynitrite that forms OH and N02 upon its decay and when C02 is present C03 and N02 (Chap. 2.4), formation of 8-oxo-G is observed (Inoue and Kawanishi 1995) and also upon peroxynitrite addition to DNA (Douki and Cadet 1996). In the latter experiments, the effect of peroxynitrite was compared with that of ionizing radiation, but although the peroxynitrite concentration applied was 1000 times the radiolytic OH yield, the 8-oxo-G and Z yields were markedly lower. Only very low 8-oxo-G yields were also detected in another study 

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