Mechanistic Modelling of Oxygen Enhancement Ratio with DNA Damage by GMicroMC
Y Lai1,2*, Y Chi2, X Jia1, (1) innovative Technology Of Radiotherapy Computation and Hardware (iTORCH) laboratory, Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75287, USA, (2) Department of Physics, University of Texas at Arlington, Arlington, TX 76019, USA
Presentations
TU-D-TRACK 6-3 (Tuesday, 7/27/2021) 2:00 PM - 3:00 PM [Eastern Time (GMT-4)]
Purpose: Oxygen plays an important role determining the radiobiological effects of ionizing radiation. It is understood that oxygen can fix damages to DNA, hence enhancing strand breaks. In this work, we used a GPU-based Monte Carlo (MC) simulation package to mechanistically model the oxygen fixation hypothesis and compute oxygen enhancement ratio (OER).
Methods: We implemented two kernel functions in gMicroMC to model the OER. The first one simulated the water radiolysis process in the presence of DNA and recorded the initial DNA damage. Chemical reactions involving oxygen was included in the simulation. The second one was a probabilistic model to capture the oxygen fixation effect on DNA damage sites. As cell survival fraction is mainly dominated by the number of DNA double strand break (DSB), we assume that the same number of DSB results in the same biological effect, OER was computed as the ratio of doses reaching the same level of DSB with and without having oxygen. We searched in the parameter space of reaction rate between damage site and oxygen, probability of repairing a damage site with/without oxygen fixation to match OER with published experimental results of photon irradiation. We applied the developed model to proton irradiation cases.
Results: Parameters was found to reaction rate 4.75×10^7 L/(mol∙s), probability of repairing with and without oxygen 0.72 and 0.92, respectively. The computed OER as a function of oxygen concentration matched with published experimental results of photon irradiation with a mean relative error 3.18%. The model gave OER of 3.04 for photon case and 2.93 for proton case at oxygen partial pressure of 15.2 mmHg.
Conclusion: We modelled OER in a mechanistic approach using microscropic MC simulations. The mechanistic modeling approach is expected to be important for understanding oxygen impacts in different scenarios, such as FLASH with multi pulses.
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