Abstract
Background: Radiation induces DNA double-strand breaks (DSBs), and chromosome aberrations (CA) form during the DSBs repair process. Several methods have been used to model the repair kinetics of DSBs including the bi-exponential model, i.e., N(t) = N1exp(−t/τ1) + N2exp(−t/τ2), where N(t) is the number of breaks at time t, and N1, N2, τ1 and τ2 are parameters. This bi-exponential fit for DSB decay suggests that some breaks are repaired rapidly and other, more complex breaks, take longer to repair. Methods: The bi-exponential repair kinetics model is implemented into a recent simulation code called RITCARD (Radiation Induced Tracks, Chromosome Aberrations, Repair, and Damage). RITCARD simulates the geometric configuration of human chromosomes, radiation-induced breaks, their repair, and the creation of various categories of CAs. The bi-exponential repair relies on a computational algorithm that is shown to be mathematically exact. To categorize breaks as complex or simple, a threshold for the local (voxel) dose was used. Results: The main findings are: i) the curves for the kinetics of restitution of DSBs are mostly independent of dose; ii) the fraction of unrepaired breaks increases with the linear energy transfer (LET) of the incident radiation; iii) the simulated dose–response curves for simple reciprocal chromosome exchanges that are linear-quadratic; iv) the alpha coefficient of the dose–response curve peaks at about 100 keV/µm.
Highlights
The RITCARD model first simulates the chromosomes using a random walk (RW) algorithm, identical to the process used in NASA Radiation Track Image (NASARTI), and simulates voxel dose in the irradiated volume using the RITRACKS (Relativistic Ion Tracks) code
The NASARTI program and the previous version of RITCARD used time steps of 5.18 s, for 24 hours. This time step was determined from prior calibration of the model, during which the double-strand breaks (DSBs) repair kinetics were fitted as a bimodal exponential curve [7]
When the repair kinetics curves are normalized to the initial number of breaks as shown in Figures 5 and 6, they essentially follow the theoretical bi-exponential curve
Summary
Ionizing radiation creates various types of DNA breaks in cells, notably double-strand breaks (DSBs). Many theories have been proposed to explain the biphasic-like shape of repair curves observed experimentally (reviewed in [1]) These theories hypothesize that two types of DNA damage exists, each characterized by a single and constant repair half-life. Aberrations, Repair, and Damage) [6] to simulate radiation-induced CAs. RITCARD uses a repair kinetics model that was carried over from the code NASA Radiation Track Image (NASARTI) [7,8]. RITCARD uses a repair kinetics model that was carried over from the code NASA Radiation Track Image (NASARTI) [7,8] This algorithm effectively simulates DSB repair, so that the number of DSBs decays as a function of time, that decay is not bi-exponential. The linear coefficient of the dose–response curve peaks at 100 keV/μm
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