Biomedical Engineering Reference
In-Depth Information
transmission measurements [ 92 ] and the peak magnitudes were scaled to reflect
the inverse energy dependence of the electron capture cross-sections. Assuming an
equal numbers of each base in DNA, the contributions from each base were simply
added. The relationship between the resonances in the base and SSB in DNA offers
support for the charge transfer mechanism proposed by Barrios et al. [ 78 ]; i.e.,
pathway 1 in Fig. 1.12 .
AsshowninFig. 1.4 , the incident electron energy dependence of the yields of
SSB and DSB induced by 5-100 eV electron impact on plasmid DNA [ 29 , 51 , 93 ]
also exhibits strong resonance features. The data were recorded in the linear regime
of the dose-response curves and hence represent SSB and DSB produced by a
single electron interaction. Whereas the DSB yield begins near 6 eV, the apparent
SSB yield threshold near 4-5 eV is due to the cut-off of the electron beam at low
energies in these experiments. Both yield functions have a peak around 10 eV, a
pronounced minimum near 14-15 eV followed by an increase between 15 and 30 eV,
and a roughly constant yield up to 100 eV. Below 15 eV, the strong peaks around
10 eV clearly show that the damage occurs via the formation of transient anions.
Above 15 eV, as shown by the dotted line, the yield increase monotonically and
saturates above 50 eV. The form of these yield functions were later understood from
the results of fragmentation induced by LEE to the various subunits of the DNA
molecule, including its structural water [ 26 ]. The strong energy dependence of DNA
SBbelow15eVinFig. 1.4 can be attributed to the initial formation of core-excited
transient anions of specific DNA subunits decaying into the DEA and/or dissociative
electronic excitation channels [ 24 , 26 ]. To date this phenomenon has been confirmed
by a large number of experiments with LEE impinging on films of DNA of various
topologies [ 25 , 26 ]. As explained in the previous section, pathway 3 of Fig. 1.12 is
expected to contribute significantly to the formation of SSB at 10 eV.
If interstrand electron transfer also occurs, it may explain how a single electron
interaction within DNA can produce a DSB with only 7-10 eV of energy as seen
from Fig. 1.4 . For example, a core-excited resonance on a phosphate group could
decay by electron transfer to the other strand while leaving behind a dissociative
electronic state breaking the C-O bond. The electron transferred to the opposite
strand could attack the sugar-phosphate backbone to cause another SB via DEA, a
process which according to Fig. 1.10 requires little energy. Such breaks on adjacent
strands would be very close to each other and hence more difficult to repair by the
cell than more distant DSB.
1.4.5
Single- and double-stranded DNA in the presence
of cellular constituents
Although vacuum experiments with dry films of pure DNA and its basic constituents
were essential to unveil fundamental mechanisms of LEE-induced damage, ex-
perimental conditions did not correspond to those found in cells. It is now well
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