Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 219

In the nucleoside and in ssDNA, G • + (p K a = 3.9) is expected to loose the proton
rapidly to the water phase, but in dsDNA pairing with Cyt will prolong its life-
time and reaction (51) may proceed with a higher efficiency. The resulting C (8)-
• OH-adduct is the precursor of the 8-oxo-G and other well-documented lesions
(see below). The same type of reaction is expected to occur with A • + (see below),
but in dsDNA Ade binding to Thy will not prevent its deprotonation at N 6 . This
may be one of the reasons why the 8-oxo-G lesion is of a higher importance than
the 8-oxo-A lesion (Chap. 12.9).
G • is readily reduced by electron donors such as TMPD, ascorbate, ABTS
(O'Neill and Chapman 1985), phenolic compounds (Jiang et al. 1999a,b; Shi et al.
1999b) or bisbenzimidazole derivatives (the Hoechst group of f fluorescent dyes;
Adhikary et al. 1997b; Martin and Anderson 1998). The good linear relationship
between the logarithm of the ET rate with the reduction potential of the donor
is evidence (O'Neill and Chapman 1985), but not proof [cf. Jagannadham and
Steenken 1988a; Steenken 1988] that this reaction proceeds via an outer-sphere
ET. At high pH, when G • is deprotonated, poorer reductants are no longer ca-
pable of reducing this intermediate (O'Neill and Chapman 1985). The reaction
of • G with NO 2 − is noticeably slower [ k = 2.6 10 6 dm 3 mol −1 s −1 ; Shafirovich et

al. 2001] than the above reactions which are close to diffusion controlled. Yet,
cellular levels of NO 2 − that are normally <2

×

10 −4 mol dm −3 may be increased to

×

10 −3 mol dm −3 under certain conditions. The product of this reaction, • NO 2 ,
oxidizes 8-oxo-G (see below).
The fate of G • in the absence of any additive is as yet unknown. It decays bimo-
lecularly with a rate constant of some 10 8 dm 3 mol −1 s −1 (Faraggi et al. 1996), but
there is increasing evidence that in competition, at least at elevated pH [p K a (G • )
= 10.8], its radical anion also decays unimolecularly [ k = 5

>1 ×

10 3 s −1 at pH 11 in
the case of Guo and dGuo; Faraggi and Klapper 1994; Faraggi et al. 1996]. The
nature of this unimolecular transformation is as yet unknown.
Unless a water-assisted disproportionation (cf. Wang et al. 1996) or a dispro-
portionation by ET takes place, G • has to dimerize. These dimers have escaped
identification, but the various canonical mesomeric forms shown below indicate

×