DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 347

von Sonntag et al. 1981; Bertinchamps et al. 1978; von Sonntag 1987), oxyl radi-
cals plus DNA (Breen and Murphy 1995), oxidative nucleobase modifications
(Burrows and Muller 1998), oxidative strand scission (Pogozelski and Tullius
1998), low-temperature EPR studies (Wyard and Elliott 1973; Hüttermann 1982,
1991; Becker and Sevilla 1998), radiation sensitizers (Brady 1980; Coleman et
al. 1988), chemical nucleases (Sigman et al. 1993a), metalloporphyrins as DNA
cleavers (Meunier 1992), photocleavage of nucleic acids (Armitage 1998) and an-
ticancer agents that form DNA radicals (Lown 1985).

12 .1.1
Inactivation of Viruses and Cells by Ionizing Radiation:
Some General Aspects

Ionizing radiation is known to inactivate viruses and cells. In the case of viruses
there are two targets, their protein coat (capsid and tail) and their nucleic acid,
DNA or RNA, respectively. Viruses are inactivated, when they are no longer ca-
pable of infecting their host cells for further propagation. When the protein coat
is damaged, the virus may no longer be able to attach to the cell to be infected, an
effect that ranges between 5% (T1 phage; Coquerelle and Hagen 1972) and 30%
(poliovirus; Ward 1980). If an attachment is still possible, the nucleic acid injec-
tion system may be impaired by protein-protein cross-linking. Injection of the
nucleic acids is equally impossible when they are cross-linked to proteins such
as the capsid. Any damage to the nucleic acids that is not repaired by the repair
system of the host cell must lead to their inactivation. However, some viruses
even carry the information for repair enzymes in their genome, but this has only
been shown so far for UV-induced damage (Yasuda and Sekiguchi 1970; Furuta
et al. 1997; Shaffer et al. 1999; Srinivasan et al. 2001).
When a virus suspension is irradiated in aqueous solution, the water radicals
formed in the bulk solution, notably • OH (Gampel-Jobbagy et al. 1972; Powers
and Gampel-Jobbagy 1972), may react with the viruses by damaging the capsid,
but they may also pass through the protein barrier and reach the nucleic acid.
The structure of the virus (T7 phage: Hawkins 1978); phage: Georgopoulos et

al. 1983; Feiss and Becker 1983) may determine which of the two processes domi-
nates. In fact, structural effects may be quite substantial. For example, in the
T-odd phages, Cu 2+ enhances the radiation sensitivity, while in the T-even series
it protects (Samuni et al. 1984). Moreover, there is an interaction of the ionizing
radiation with the virus particle. The importance of this process with respect
to inactivation increases with an increase in the scavenger concentration that
eliminates the water radicals formed in the bulk solution (for a study comparing
the sensitivity of phages to UV and ionizing radiation, see Sommer et al. 2001).
With cells, the situation is quite different. There, the DNA is not near the
surface, and very reactive radicals generated in the bulk solution, such as • OH,
cannot reach it. Therefore, these exogenous • OH do not contribute to cell killing.
Saturation with N 2 O that doubles the bulk • OH yield has no effect on survival
(Antoku, 1983), and only the endogenous • OH formed near the DNA have to be
considered (Jacobs et al. 1985). These experiments already show that damage of
the cell's outer membrane cannot be of major importance. Although damage to

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