DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 348

Table 12.2. Dose (Gy) absorbed in the nucleus, cytoplasm and membrane of CHO cells
at LD 50 levels of mortality (Warters et al. 1977). 3 H-dThd was incorporated into the DNA,
whereas 125 I-concanavalin was associated with the membrane. X-rays were from an exter-
nal source

Subcellular dose/Gy

Radiation source Nucleus Cytoplasm Membrane

X-ray 3.3 3.3 3.3

3 H-dThd

3.8 0.27 0.01

125 I-concanavalin

4.1 24.7 516.7

the outer cell membrane is of comparatively little consequence at least in mam-
malian cells (see below), there is a marked effect membrane composition (f (fluid-
ity?) on the radiation sensitivity (Edwards et al. 1984; George et al. 1980; Yatvin
et al. 1972, 1979, 1984, 1987; Yatvin 1976; ; Yatvin and Grummer 1987). Details
of this most interesting effect are as yet not fully elucidated, but attention has
been drawn to the fact that DNA is attached to membranes, in eukaryotic cells,
for example, to the nuclear membrane. Whether the membrane-mediated dam-
age is due to free-radical reactions such as membrane/DNA interactions, has a
marked effect on repair or is due to any other process seems to be still an open
question.
The view that DNA is the most important target as concerns cell killing by
ionizing radiation has been derived from a microdosimetric approach (Cole et
al. 1980). With eukaryotic cells that contain their DNA in the nucleus, little lethal
damage is observed as long as the ionizing radiation is absorbed in the mem-
brane or in the cytoplasm. There is a dramatic increase as soon as the ionizing
radiation reaches the nucleus (Cole 1965; Munro 1970; Datta et al. 1976). DNA as
the most prominent lethal target is supported by experiments, where total-cell
irradiation (X-rays) is compared with the effects of radioactive nuclei emitting
only short-range ionizing radiation that were placed at either the membrane or
incorporated into DNA (Table 12.2).
It is seen from this table that, at the LD 50 level, the nucleus has received about
the same dose, irrespective of whether X-rays, 3 H-dThd or 125 I-concanavalin are
used as the source of ionizing radiation, while the membrane has received an
immense dose with 125 I-concanavalin and very little with 3 H-dThd. As expected,
the cytoplasm lies in between these two extremes. Yet, irradiation of the cyto-
plasm (single-ion-beam experiments) is not without an effect. It may cause mu-
tations (Wu et al. 1999) and the formation of products that induce apoptosis in
nearby (unirradiated) cells (bystander effect ;Shao et al. 2004).
In the interaction of ionizing radiation with DNA one distinguishes between
the direct effect (absorption of the ionizing radiation by DNA) and the indirect