DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 375

The minor-grove-binding artificial nuclease Mn-TMPyP when activated with
KHSO 5 gives rise to 5-MF as well as furfural with concomitant release of unal-
tered nucleobases (Pratviel et al. 1991; Pitié et al. 1995). This reaction is also giv-
en by ODNs, and there is a strong variation of the 5-MF to furfural ratio in these
systems indicating that structural differences determine the site of attack. While
the formation of 5-MF is considered to be due to an attack at C (1

′ ) (Sect. 12.9.4),

furfural formation is suggested to start from an attack at C (5 ′ ) [reactions (36)

and (37)].

Oxidation at C (5 ′ ) normally leads to the formation of the 5 ′ -aldehyde, and the

fact that the subsequent -elimination and base release processes are observed

may indicate that Mn-TMPyP has catalytic properties besides an oxidative pow-
er.

β

-radiolysis of plasmid DNA in aerobic aqueous solution, SSB formation
is mainly due to the reaction of • OH with DNA. In the absence of any scavengers,
an efficiency of 0.12 per • OH reacting with DNA has bee measured (Milligan et
al. 1993b; 0.11 for ssDNA in the presence of N 2 O/O 2 (0.15 in the presence of N 2 O);
Liphard et al. 1990; 0.14

In the γ

0.22 at low scavenger concentrations; van Rijn et al.
1985). A variation of the concentration of added scavengers cannot be described
by simple competition kinetics (Milligan et al. 1993b; Klimczak et al. 1993) but
is in good agreement with a non-homogeneous kinetic model (Udovicic et al.
1991a; Mark et al. 1989). The efficiency of SSB-induction per • OH-interaction
with DNA (0.32-0.44) is essentially identical for all investigated plasmids (Mil-
ligan et al. 1993b). An effect of the superhelical density is also not pronounced
(Milligan et al. 1992). The non-homogeneous kinetic model can also be applied
to SV40 minichromosomes where part of the DNA is protected by the histones
(efficiency 0.04-0.05; Milligan et al. 1993a). The about threefold increase in the
SSB induction efficiency upon going from scavenger-free aqueous DNA solu-
tions to scavenger-containing ones is not yet fully understood. Obviously, the
scavenger-free DNA solutions must always contain some impurities that could
reduce the • OH-yield available for reacting with DNA, but it is difficult to visual-
ize contaminations as high as required for factor near 2-3.
When dsDNA is

−

-irradiated in dilute aqueous solution in the absence of
scavengers only SSBs are formed at low doses and DSBs only become noticeable
at higher doses, their yield being proportional to the square root of the dose
(Hagen 1967). Under such conditions, DSBs arise from too nearby SSBs that have
been created in two independent events. When • OH-scavenger are added, strand
breakage is markedly reduced, but upon raising the scavenger concentration the
DSB/SSB ratio increases. The formation of DSBs at high scavenger concentra-

γ