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Open AccessArticle

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

1
KBR, 2400 NASA Parkway, Houston, TX 77058, USA
2
NASA Langley Research Center, Hampton, VA 23681, USA
3
Radiation Institute for Science & Engineering, Prairie View A&M University, Prairie View, TX 77446, USA
*
Author to whom correspondence should be addressed.
Genes 2019, 10(11), 936; https://doi.org/10.3390/genes10110936
Received: 20 September 2019 / Revised: 1 November 2019 / Accepted: 12 November 2019 / Published: 16 November 2019
(This article belongs to the Special Issue DNA Damage and Repair after Radiation)
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. View Full-Text
Keywords: DNA double-strand breaks; ionizing radiation; repair kinetics; bi-exponential; chromosome aberrations DNA double-strand breaks; ionizing radiation; repair kinetics; bi-exponential; chromosome aberrations
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Plante, I.; Slaba, T.; Shavers, Z.; Hada, M. A Bi-Exponential Repair Algorithm for Radiation-Induced Double-Strand Breaks: Application to Simulation of Chromosome Aberrations. Genes 2019, 10, 936.

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