DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 426

Table 12 . 24. RBE and OER values for cell inactivation and induction of DSBs in V79-4 cells
on the photon energy of the ultrasoft X rays. (de Lara et al. 2001)

RBE OER

Radiation type Energy Survival (10%) DSBs Survival (10%) DSBs

60 Co- γ rays

1.17/1. 33 MeV 1 1 2.8 3.5

Ti K-shell X rays 4.55 keV 1.5 1.4 2.0 1.9

Al K-shell X rays 1.49 keV 1.7 1.9 1.9 2.1

Cu L-shell X rays 0.96 2.3 2.3 2.0 1.8

C K-shell X rays 0.28 keV 2.8 2.7 2.2 1.8

consequence, the reaction is comparatively slow and may become effective only
under certain conditions. For example, one may envisage that the DNA radical
happens to be in quasi-contact with the peptide C H of a surrounding protein

and the latter shields the DNA radical from an approach by O 2 or GSH. The life-
time of the O 2 -dependent DNA damage has been given as 0.2 ms in Table 12.18.
Taking the 'peptide concentration' as 10 mol dm − 3 (i.e. a quasi-solvation of the
DNA radical by peptide C

−

H groups of the surrounding protein), one would ar-
rive at a rate constant of only 3.5

−

10 2 dm 3 mol −1 s −1 to become competitive.
According to the data given for the lac suppressor

×

lac operator complex (cf.
Begusova et al. 2001a) at least one peptide hydrogen may came close enough
(3.45 Å, near

−

3.4 Å the crystallographic distance, where H-transfer has been
observed in chain reactions passing through carbohydrate crystals such as 2-de-
oxyribose; Schuchmann et al. 1981 and D-fructose; Dizdaroglu et al. 1976). Yet,
the observed protection at the given position can be adequately described by the
RADACK procedure (Sect. 12.2.1), and there is not yet experimental evidence for
protection and repair beyond radical scavenging and induction of conforma-
tional DNA changes.
As the LET of the ionizing radiation increases, the RBE increases as do clus-
tered lesions such as DSBs. The presence of O 2 has then no longer such a dom-
inating effect on increasing the complexity of DNA lesions and thus the OER
drops. This is exemplified for ultrasoft X-rays in Table 12.24.

≤

12 .12 . 3
Sensitization

It has been pointed our above that solid tumors may have a hypoxic core (for the
detection of hypoxic regions see Porschen et al. 1977; Chapman 1984), and that it
would be highly desirable to sensitize these areas with a drug that is not as rapid-
ly metabolized as O 2 and therefore can reach the site of action and mimic O 2 with
respect to its capability to fix DNA damage. Many of the drugs that have been