Biomedical Engineering Reference
In-Depth Information
section, if we attribute the increase damage to electron capture by cisplatin. Since
only two cisplatin molecules per 3197 base pairs increase damage by a factor of
1.4, the capture cross section must be orders of magnitude higher at the site of
cisplatin. The cisplatin molecule has a shape resonance near zero eV which leads
to DEA, but the magnitude of the process is not known [
118
]. Close to zero eV,
DEA cross sections often reach huge values of the order of
10
15
cm
2
owing
to the 1/k momentum factor, which enters into the expression of the captured cross
section [
119
-
121
]. Furthermore, in DNA this cross section could be increased by
base to base electron transfer along the chain, which would act to draw additional
electrons to the site of cisplatin. This idea that a modified molecular site may
act as a sink for non-thermal electrons has previously been tested by doping the
surface of solid saturated hydrocarbon films with a simple molecule having a shape
resonance at low energy [
122
,
123
]. In the case of an n-hexane surface doped by O
2
,
electron capture by O
2
was increased by four orders of magnitude [
122
]. Another
possible explanation for the large EF obtained with only two cisplatin molecules
may be related to modifications induced in DNA by cisplatin. Cisplatin modifies the
topology of DNA, which could weaken certain bonds and promote DEA within the
backbone [
117
].
From the results shown in Fig.
1.4
and the explanations in subsection
1.4
,the
large EF plotted in Fig.
1.16
at 10 eV can be interpreted as due to an increase in the
formation of SSB and DSB caused by the formation of core-excited resonances. At
10 eV, the exact process which is enhanced by the presence of cisplatin may
apriori
arise from pathways 1 and 3 in Fig.
1.12
. Since pathway 1 is not very effective above
3 eV, it is probably the mechanism of pathway 3 that is enhanced by the presence
of cisplatin. Replacing pathway 1 by pathway 3, the rest of the explanation for the
10 eV enhancement process becomes similar to that for 1-eV electrons.
As seen from Fig.
1.4
, above 15 eV both the SSB and DSB yields rise monotoni-
cally from an apparent threshold and reach a plateau near 30 eV. Above 30 eV, many
nonresonant mechanisms exist that can contribute to the observed DNA damage,
such as transitions to excited states of the neutral molecule or its cations. The
possible reactions are shown for a molecule RH by pathways 1 and 2 in Fig.
1.2
.
Hence, there exists a plethora of reactions that could be enhanced by the presence
of cisplatin in DNA and would contribute to the EF shown in Fig.
1.4
at 100 eV. It
is impossible, in this case, to determine which reactions are increased by binding
cisplatin to DNA. However, according to the EF in Fig.
1.16
, cisplatin increases
more resonance processes at 10 eV leading to SSB than those occurring at 100 eV.
Contrary to the behavior of the EF for SSB, the EF for DSB increases from
10 to 100 eV. This behavior may seem strange since the probability to cut each
individual strand must decrease according to the data for SSB. However, owing to
the large ionization cross section at 100 eV [
30
], a single 100 eV electron can induce
considerable multiple ionizations. With LEE thermalization distances of the order
of the film thickness [
5
,
124
], the probability of breaks occurring on adjacent chain
sites by one or more SE created from ionization by the initial 100 eV electron or a
SE is high and probably accounts for the higher EF for DSB at 100 eV. Moreover,
10
13
-
