Program Information
A Mathematical Approach to Model Double Strand Break Repair Kinetics Induced by Proton and Carbon Ions
R Taleei1*, (1) UT Southwestern Medical Center, Dallas, TX
Presentations
MO-L-GePD-TT-1 (Monday, July 31, 2017) 1:15 PM - 1:45 PM Room: Therapy ePoster Theater
Purpose: Proton and carbon therapy are becoming the two main choices of particle therapy for cancer treatment, however the basic biology of cellular damage and cell death is not well understood. The aim of this work is to present a mechanistic model of double strand break (DSB) repair that predicts the repair kinetics damage induced by proton and carbon.
Methods: Monte Carlo Track Structure simulation was employed to model DNA damage in a cell model. Direct and indirect damage to a DNA model inside a cell was computed for different ions including proton, and carbon ions. The DSB were subjected to repair model to calculate the repair kinetics. Two distinct DSB repair models dependent on the cell cycle were proposed. The repair model was transformed to a set of differential equations. The model calculates the overall repair kinetics and protein temporal repair activity at the site of damage.
Results: The repair kinetics were calculated for proton, carbon ions and compared with experimental data. DSBs are repaired by non-homologous end joining (NHEJ), homologous recombination (HR), and back up non-homologous end joining (B-NHEJ). The DSB complexity results in switch in the repair pathway from NHEJ to a slower process that starts with DSB end resection. DSB end resection in early S and G1 phases of the cell cycle enhances the B-NHEJ repair pathway, while in late S and G2 phases of the cell cycle promotes HR repair pathway. The repair kinetics were in good agreement in comparison to the experiments.
Conclusion: The damage and repair model for proton and carbon ions provides a detailed and mechanistic understanding of all processes that are involved the damage induction. The agreement between the calculations and measurements confirmed the assumption that complex DSB play an essential role in cellular fate after radiation damage.
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