Polynucleotides and Single-Stranded DNA Fragments - Free-Radical-Induced DNA Damage and Its Repair - page 324

11.1
General Remarks
Polynucleotides have been widely studied as a model system for DNA. However,
only the ribo-series is available at reasonable costs, and for this reason more
detailed studies have been largely carried out with poly(U), poly(C), poly(A),
and poly(G). In water, these polynucleotides remain largely single-stranded with
the exception of poly(G) which has a tendency to aggregate, even above double-
strandedness. This has made these polynucleotides, especially poly(U), the pre-
ferred tool to study the kinetics of radical-induced strand breakage, when it had
been discovered that this process is connected with a change in conductivity
and thus could be readily followed by pulse radiolysis (Bothe and Schulte-Froh-
linde 1982; Chap. 13.3). Although these studies have yielded very important in-
formations, the ribo -polynucleotides show some properties not given by DNA,
not even by ssDNA. As a consequence, polydeoxyribonucleotides and smaller
ODNs are finding increasing attention as DNA model systems. The OND nucleo-
tide sequence can be designed to remain either ss or to form stable dsDNA sec-
tions with the advantage that they are small enough for a detailed analysis of the
ongoing processes. These studies have become possible only during more recent
years, when automated DNA synthesis became a well-established technique and
these ODNs more reasonably priced. When appropriate, the results of the studies
using dsODNs are discussed in Chapter 12.
In the present chapter, it will be shown that in the polynucleotides reactions
take place that are not apparent on the nucleotide level (Chap. 10). The increas-
ing number of reactions available to polymer-derived radicals (Chap 9) renders
the free-radical chemistry of polynucleotides and ODNs more complex than that
of the corresponding nucleotides. Nevertheless, our understanding of mecha-
nistic details is not on a much lower level, because with polymers the pulse radi-
olysis technique (Chap. 13.3) provides additional information.
11. 2
Hydroxyl-Radical-Induced Reactions
11. 2 .1
Small Oligonucleotides
The number of studies on ssODNs is rather low, but important information as to
the formation of tandem lesions has been obtained with these systems.
In the reaction of • OH with d(TpApCpG) in oxygenated aqueous solution
the Fo lesion, the Cyt-derived 1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine
modification and 8-oxo-G were observed (Paul et al. 1988). In the presence of
GSH and in the absence of O 2 , the major detected modification is 5OHH 2 Thy
(Paul et al. 1990).
With d(ApCpGpT) X-irradiated in N 2 -saturated solution the H 2 Thy,
6OHH 2 Thy, Tg, 8-oxo-G and cA modifications were detected (Schroder et al.
1995). In the presence of O 2 , the observed modifications were 8-oxo-G, 8-oxo-A,