A Bi-Exponential Repair Algorithm for Radiation-Induced Double-Strand Breaks: Application to Simulation of Chromosome Aberrations

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) = N(1)exp(−t/τ(1)) + N(2)exp(−t/τ(2)), where N(t) is the number of breaks at time t, and N(1), N(2), τ(1) and τ(2) 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.