Biomedical Engineering Reference
In-Depth Information
modelled as 3-
m radius spheres. The 46 chromosome territories are described
as (irregular) intra-nuclear domains with volume proportional to the chromosome
DNA content, and each territory consists of the union of small adjacent cubic
boxes. Repetition of chromosome territory construction with different chromosome
positions provides different configurations for lymphocyte nuclei in the G
0
phase of
the cell cycle.
The yield of induced CL
cell
1
is the starting point for dose-response-
curve simulations. While for photons the lesions are randomly distributed in the
cell nucleus, for light ions they are located along straight lines representing the cell
nucleus traversals. Concerning heavy ions, which are still “work in progress”, as a
first approach a fraction of the lesions induced by a heavy ion are “shifted” radially
to model the effects of the so-called “delta rays”, which play a significant role in
determining the features of heavy particle tracks. For a given dose
Gy
1
D
(in Gy), the
n D D r
2
/(0.16 LET)
average number of cell nucleus traversals
n
is calculated by
where the LET is expressed in keV/
m) represents either the cell
nucleus radius (for light ions), or the nucleus radius plus the maximum range of delta
rays (for heavier ions). An actual number is extracted from a Poisson distribution.
For each cell nucleus traversal, random extraction of the point where the particle
enters the nucleus provides the traversal length, being the direction fixed (parallel
irradiation).
The average number of CLs per unit length along a cell nucleus traversal is
calculated as CL/
mand
r
(in
Gy
1
cell
1
V
1
, where V is the cell
m
D 0:16
CL
LET
m
3
. For each nucleus traversal, a Poisson distribution provides
an actual number of lesions. Comparison of the CL positions to those of the boxes
constituting the chromosome territories allows association of the lesions to the vari-
ous chromosomes. Specific background (i.e. prior to irradiation) yields for different
aberration types (typically 0.001 dicentrics/cell and 0.005 translocations/cell) can
be included. Both Giemsa staining and whole-chromosome FISH painting can be
simulated, and the implementation of multi-FISH is in progress. Small fragments,
i.e. with size of about 10 Mbp, are not scored when the simulation outcomes are to
be compared with experimental data, since these fragments can hardly be detected
in experiments. Simulation of CL induction and rejoining for a sufficiently high
number of times provides statistically significant aberration yields. Repetition of
the process for different dose values allows obtaining dose-response curves for the
main aberration types, directly comparable with experimental data.
In previous works the model has been tested for gamma rays, protons and He ions
by comparing simulated dose-response curves with experimental data available in
the literature, without performing any fit
a posteriori.
The good agreement between
model prediction and experimental data for the induction of different aberration
types allowed for model validation regarding both the adopted assumptions and
the simulation techniques. Furthermore, the model has been applied to evaluate
the induction of Chronic Myeloid Leukaemia [
54
] and to estimate dicentric
chromosomes observed in lymphocytes of astronauts following long-term missions
onboard the Mir space station and the International Space Station, on the basis of
simulated gamma-ray dose response weighted by the space radiation quality factor
nucleus volume in
