Nucleobases, Nucleosides and Nucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 256

et al. 1986). The second step will be much slower and may only occur during the
work-up (cf. the slow - and proton-catalyzed - water elimination of bis(hydroxy
cyclohexadienyl) into biphenyl; Mark et al. 2003).
These reactions are only trivial as far as their chemistry is concerned (re-
combination of radicals and subsequent water elimination). This does not mean,
however, that these reactions are of little importance in cellular-DNA free-radi-
cal chemistry.
It will be shown below that alkyl radicals add predominantly at the C (6)-po-
sitions of the pyrimidines and, when products as shown above are found after
• OH-attack in very complex systems such as nucleohistones (e.g., Gajewski et al.
1988; Dizdaroglu and Gajewski 1989; Dizdaroglu et al. 1989; Gajewski and Dizd-
aroglu 1990) or Thy dimers in polydeoxythymidylic acid (Karam et al. 1986), it
cannot be fully excluded that they are formed via the trivial two-radical recom-
bination mechanism.
One of the first • OH-induced purine damage detected was in the 5

,8-cyclo-
nucleotides. This lesion was later also observed in DNA (Chap. 12.5). In the fol-
lowing, the non-trivial case, the reactions of organic radicals with pyrimidines
and purines will be discussed, and a special section will devoted to 5

′

,8-cyclo-
nucleosides and nucleotides whose mechanism of formation has been found to
be very complex.

′

Pyrimidines. Alkyl radicals are nucleophilic radicals and add to the C (6)-posi-
tion of pyrimidines rather than to the C (5)-position as the electrophilic • OH and
H • do. The reactions of pyrimidines with

-hydroxyalkyl radicals that can be
readily generated photolytically or radiolytically have been investigated inten-
sively (Brown et al. 1966; Zarebska and Shugar 1972; Leonov et al. 1973; Frimer
et al. 1976; Shetlar 1976, 1979, 1980; Ekpenyong and Shetlar 1979; Cadet et al.
1981; Ishida et al. 1985, 1986; Schuchmann et al. 1986). In the earlier radiolytic
studies (Brown et al. 1966; Zarebska and Shugar 1972; Cadet et al. 1981), e aq − had
been scavenged by the pyrimidines, and thus the pyrimidine electron adducts
took part in the reactions. This has been avoided in a later study on the reactions
of • CH 2 OH with 1,3Me 2 Ura and 1,3Me 2 Thy (Schuchmann et al. 1986), and the
subsequent discussion is based on these results.
In the case of 1,3Me 2 Ura, all products (Table 10.21) can indeed be accounted
for if in the primary step • CH 2 OH adds to the C (6) position [reaction (190)].

α

There is a considerable effect of the G values on the dose rate, and from this
dose rate dependence it has been calculated that the rate constant of the addi-
tion of • CH 2 OH to 1,3Me 2 Ura must be about 1 10 4 dm 3 mol −1 s −1 . Thus, the

rate of this reaction is five orders of magnitude lower than that of • OH. Even at

×