Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 289

low an assignment of the various components to certain intermediates. Potential
intermediates have been discussed in the preceding paragraphs.
Further base release data are compiled in Table 10.31. There is a considerable
spread in these values among the various nucleosides/nucleotides even under
seemingly same experimental conditions. Part of this variation could be due to a
change in the ratio of • OH attack at the base vs sugar moieties. The time elapsed
between irradiation and work-up may also play a role (see Table 10.30). Com-
pared to the 2

′ -deoxynucleosides, an additional site, C (2 ′ ), is likely to contribute.

There is a dramatic difference between Ado and Ado-3 -P. Phosphate release

may here compete with base release. Further data are required to put this sug-
gestion on a better footing.

′ ,5 ′

10.9
Oxidation of Nucleobase/Sugar Radicals
by Radiation Sensitizers

The oxidation of DNA radicals by hypoxic sensitizers, normally nitro com-
pounds, has found considerable interest in the context of attempts to improve
irradiation regimes in the radiotherapy of solid tumors (Chap. 12.11). Concomi-
tantly, model studies have been undertaken in order to shed some light on poten-
tial mechanism of their reactions. p -Nitroacetophenone (PNAP) has often been
used as a convenient model sensitizer.

The radicals derived from 2-deoxyribose (ribose) upon • OH-attack yield 37%
(23%) PNAP • − , and it has been concluded that ET only occurs from the C (1 )

radicals (Michaels et al. 1976). With • CH 2 OH/CH 2 O • − the rate of reaction with
PNAP is only fast with the anion, CH 2 O • − (Adams and Willson 1973). Whether
the radicals formed at the other sites in 2-deoxyribose and ribose give (slow-
ly) rise to adducts cannot be deduced from the reported data. Yet, the fact that
PNAP enhances the yield of free phosphate in the radiolysis of GMP (Greenstock
et al. 1973a) is an indication that such adducts are likely to be formed, but the
rate of reaction is very slow with

′

10 7 dm 3 mol −1

α -phosphatoalkyl radicals (< 5 ×

s −1 ; Schuchmann et al. 1995).
Practically no ET to PNAP occurs from the reducing Ura-6-yl Cyt-6-yl rad-
icals, but the (protonated) Cyt electron adduct gives rise to PNAP • − (Hissung
and von Sonntag 1979). As mentioned above, the (protonated) electron adduct of
dAdo is also rapidly oxidized by PNAP, but upon ET, dAdo is not reformed (His-
sung et al. 1981a). Possibly, the resulting product retains the elements of water.
With a nitro compound that has a higher reduction potential than PNAP, e.g.,
nifuroxime, the rate of reaction with various radicals seems to be always near dif-
fusion-controlled, and there is a competition between ET and adduct formation