Biomedical Engineering Reference
In-Depth Information
at 50% [
57
]. From the experiments of de Lara et al., one can estimate that 40-50%
of the lesions induced in DNA by low linear energy transfer radiation arise from
direct energy deposition events, many of which ionize DNA [
58
]. In other words,
if we assume that the direct effects of radiation in cells corresponds to the damage
measured by Brun et al. in vacuum with X-rays, we deduce from Table
1.1
a 49%
and 61% contribution of the indirect effect (i.e., that caused by the presence of water
molecules).
More recently, using the apparatus shown in Fig.
1.9
, Alizadeh et al. [
56
]
measured DNA damage induced by LEE and soft X-rays under dry nitrogen and
oxygen at atmospheric pressure and temperature. Five-ML plasmid DNA films
deposited on tantalum and glass substrates were exposed to Al K
'
X-rays of 1.5 keV
in the two different environments. From the yields, G values were extracted for
X-rays and LEE. In the gaseous N
2
environment, the
G
values were found to be
65 ˙ 6
J for LEE. These values agreed
with those obtained for SSB in similar experiments under vacuum [
107
]andshow
similarity between vacuum and N
2
environments. Thus, it appears that the excited
species produced by 1.5 keV photons and LEE in the N
2
atmosphere surrounding
DNA did not largely contribute to the damage. Under the O
2
nmol
=
J for X-rays and
227 ˙ 15
nmol
=
atmosphere,
G
values
were
J for X-rays and LEE, respectively, i.e., in an
oxygenated atmosphere the G values were 1.9 and 1.8 higher than the corresponding
values in a nitrogenated environment, respectively. The results of Alizadeh et al.
[
56
] also indicated a higher (
124 ˙ 9
and
415 ˙ 15
nmol
=
-fold) effectiveness for LEE relative to 1.5 keV X-
rays in causing SSB in both environments. These authors discussed their results by
considering reactions with DNA of the species created by the radiation in gaseous
N
2
and O
2
and oxygen fixation of primary damage. From these considerations,
they suggested that the oxygen fixation mechanism, which is highly effective in
increasing radiobiological effectiveness, under aerobic conditions, is operative on
the type of damage created at the early stage of DNA radiolysis (i.e., at times
t
3
<10
12
s) by LEE.
1.5
Low energy electrons in concomitant chemoradiation
therapy (CRT)
5
0
fluorouracil and cisplatin, it has
been demonstrated that treatments with a chemotherapeutic drug delivered with con-
current radiation increased the survival of patients as compared to non-synchronal
treatments [
35
,
111
]. This observation has been attributed to a superadditive effect
on tumor regression, due to a synergistic interaction between the radiation and
the drug. Superadditive effects in concomitant CRT are expected to depend on
the ways different drugs can increase the effects of radiation. The case of the
chemotherapeutic agent cisplatin [
112
] is discussed in this section. Essentially two
mechanisms have been proposed to explain the observed superadditive effect of
In many clinical studies with agents such as
