Biomedical Engineering Reference
In-Depth Information
still not clear whether any DNA double-strand break (DSB) can participate in the
formation of chromosome aberrations, or if more severe (i.e. clustered) breaks are
required. Furthermore, while it is widely recognised that only breaks sufficiently
close in space can interact and form exchanges, the relationship linking the initial
distance between two breaks and their interaction probability is still not known.
Both exponentially-decreasing functions and step functions were applied with equal
success, though the latter seem to receive more support by the experimental evidence
that DNA repair - including misrepair - mainly takes place in repair factories
located in the small channels separating the various chromosome territories. Another
object of debate is the possibility of having an exchange starting from a single
radiation-induced chromosome break, which may lead to a (simple) exchange-
type aberration mediated through subsequent induction of a second break by the
enzymatic mechanisms involved in DNA repair [
45
].
Theoretical models and simulation codes can be of great help both as interpre-
tative tools, for elucidating the underlying mechanisms, and as predictive tools, for
performing extrapolations where experimental data are not available, typically at
low doses and/or low dose rates. Various modelling approaches can be found in the
literature; many of them are based on Lea's “Breakage-and-Reunion” theory [
46
].
Though the Revell's “Exchange Theory” was applied by various authors, the models
based on Lea's approach better describe the induction of complex exchanges.
Various reviews on chromosome aberration induction theories and models are
available in the literature [
47
-
50
]. In the next section, we will present two of the
few modelling approaches that can deal with heavy ions, since the vast majority of
the available works are limited to photons and/or light ions.
22.3.1
A model based on interphase chromosomes
and DSB production and rejoining
In 2002, Chatterjee and co-workers published a modelling work on chromosome
aberration induction in human lymphocytes exposed to different radiation types
including heavy ions [
51
]. The model explicitly takes into account interphase chro-
mosome structure, intra-nuclear chromosome organization, and DSB production
and rejoining in a faithful or unfaithful manner. More specifically, each of the 46
human chromosomes is modelled as a random polymer inside a spherical volume.
The chromosome spheres are packed randomly within a spherical nucleus, with an
allowed overlap degree controlled by a parameter
.
The induction of DSBs was modelled on the basis of radiation track-structure,
and chromosome exchanges were assumed to arise from pairwise mis-rejoining of
close DSB free-ends. Rejoining was modelled by a Monte Carlo procedure using
a Gaussian proximity function controlled by an interaction range parameter
.The
parameters were fixed
a posteriori
by fitting the model predictions to experimental
data. With an overlap parameter of
¢
0:675
m and an interaction range of
0:5
m,
