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Updated: Oct 22, 2025
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Published on: May 27, 2016
Modeling of cellular response after FLASH irradiation: a quantitative analysis based on the radiolytic oxygen
Hongyu Zhu1,2,3, Junli Li2,3, Xiaowu Deng1
1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People's Republic of China.
Abstract:
Purpose.Recent studies suggest ultra-high dose rate (FLASH) irradiation can spare normal tissues from radiotoxicity, while efficiently controlling the tumor, and this is known as the 'FLASH effect'. This study performed theoretical analyses about the impact of radiolytic oxygen depletion (ROD) on the cellular responses after FLASH irradiation.Methods.Monte Carlo simulation was used to model the ROD process, determine the DNA damage, and calculate the amount of oxygen depleted (LROD) during FLASH exposure. A mathematical model was applied to analyze oxygen tension (pO2) distribution in human tissues and the recovery of pO2after FLASH irradiation. DNA damage and cell survival fractions (SFs) after FLASH irradiation were calculated. The impact of initial cellular pO2, FLASH pulse number, pulse interval, and radiation quality of the source particles on ROD and subsequent cellular responses were systematically evaluated.Results.The simulated electronLRODrange was 0.38-0.43μM Gy-1when pO2ranged from 7.5 to 160 mmHg. The calculated DNA damage and SFs show that the radioprotective effect is only evident in cells with a low pO2. Different irradiation setups alter the cellular responses by modifying the pO2. Single pulse delivery or multi-pulse delivery with pulse intervals shorter than 10-50 ms resulted in fewer DNA damages and higher SFs. Source particles with a low linear energy transfer (LET) have a higher capacity to deplete oxygen, and thus, lead to a more conspicuous radioprotective effect.Conclusions. A systematic analysis of the cellular response following FLASH irradiation was performed to provided suggestions for future FLASH applications. The FLASH radioprotective effect due to ROD may only be observed in cells with a low pO2. Single pulse delivery or multi-pulse delivery with short pulse intervals are suggested for FLASH irradiation to avoid oxygen tension recovery during pulse intervals. Source particles with low LET are preferred for their conspicuous radioprotective effects.
