A Mechanistic Model for the Calculation of Oxygen Dependent DNA Damage After Radiation Exposure
H Zhu1*, J Li2, X Deng1, R Qiu2, Z Wu2, H Zhang2, (1) Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Gangzhou, Guangdong, CN, (2) Department of Engineering Physics, Tsinghua University, Beijing, CN,
Presentations
WE-IePD-TRACK 5-4 (Wednesday, 7/28/2021) 12:30 PM - 1:00 PM [Eastern Time (GMT-4)]
Purpose: Cellular responses at different oxygen concentrations (OCs) continues to be of significant research interest in cancer radiobiology. Therefore, this study aimed to develop a mechanistic model for the analysis of cellular responses at various OCs.
Methods: A DNA damage model (the different cell oxygen level DNA damage [DICOLDD] model) that examines the oxygen effect was developed based on the oxygen fixation hypothesis, which states that dissolved oxygen can alter the reaction kinetics of DNA-derived radicals generated by ionizing radiation. Radiation induced DNA-derived radicals were simulated using the Monte Carlo method, and the decay of DNA-derived radicals was described using differential equations. The DICOLDD model was fitted to previously published experimental data obtained under different irradiation configurations. Furthermore, the DICOLDD model was validated by calculating yields of DNA double strand breaks (DSBs) after exposure to 137Cs as well as cell survival fractions (SFs) after exposure to different particles.
Results: Generally, DSB yields calculated after exposure to 137Cs at different OCs correspond to statistical uncertainties of previous experimental results. Calculated cell SFs exposed to photons, protons, and alpha particles at different OCs concur with those obtained in previous studies. Moreover, the DICOLDD model was applied for the calculation of DNA damage yields after irradiation with 0.5–50 MeV protons. Our results demonstrated that the variation in DSB yields was less than 10% when the cellular OC decreased from 21% to 5%. Additionally, DSB yields changed drastically when OC dropped below 1%.
Conclusion: We developed a DNA damage model to evaluate the oxygen effect and evidenced that it provides a mechanistic description of the reaction kinetics of DNA-derived radicals induced by ionizing radiation. Therefore, the DICOLDD model could be a powerful tool for the analysis of cellular responses at different OCs after exposure to different types of radiation.
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Taxonomy
TH- Radiobiology(RBio)/Biology(Bio): RBio- general
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