| Han Xu,Liu Zhiqiang,Zhang Qinghua,et al.Prediction of DNA damage and cell survival rate after carbon ion irradiation for A549 cells using Geant4-DNA[J].Chinese Journal of Radiological Medicine and Protection,2026,46(3):246-255 |
| Prediction of DNA damage and cell survival rate after carbon ion irradiation for A549 cells using Geant4-DNA |
| Received:November 06, 2024 |
| DOI：10.3760/cma.j.cn112271-20241106-00427 |
| KeyWords:Geant4-DNA Carbon ions DNA damage Cell survival rate prediction Relative biological effects (RBE) |
| FundProject:中央引导地方科技发展资金项目(24ZYQA029);兰州市科技计划项目(2025-4-026,2023-1-9);甘肃省科技计划项目(22CX8JA149);国家自然科学基金青年学生基础研究项目(123B2090) |
| Author Name | Affiliation | E-mail | | Han Xu | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000, China | | | Liu Zhiqiang | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000, China
Lanzhou Taiji Ion Technology Co., Ltd., Lanzhou 730000, China | | | Zhang Qinghua | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000, China | | | Zuo Zijie | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000, China | | | Yang Zhen | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
University of Chinese Academy of Sciences, Beijing 100049, China | | | Luo Hongtao | University of Chinese Academy of Sciences, Beijing 100049, China | | | Sun Shilong | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China | | | Zhang Qiuning | Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
Lanzhou Taiji Ion Technology Co., Ltd., Lanzhou 730000, China
Gansu University of Chinese Medicine, Lanzhou 730000, China | zhangqn@impcas.ac.cn |
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| Abstract:: |
| Objective To establish an experimental data-driven framework for predicting the biological effects of carbon ion irradiation on A549 cells by modeling early DNA damage and predicting cell survival rates through Monte Carlo simulations. Methods Firstly, based on the Monte Carlo tool Geant4-DNA, a A549 cell and nuclear DNA model was established, and a 6.4 Gbp chromatin fiber structure was generated through Hilbert curve iteration. GATE was then used to simulate the energy spectrum and dose-averaged linear energy transfer (LETd) distribution of a 120.26 MeV/u monoenergetic carbon ion beam in water phantoms of various thicknesses. Based on the carbon ion energy spectrum information, the cell irradiation damage under different LETd conditions was simulated using Geant4-DNA. Finally, based on the experimental data of A549 cells, the damage repair parameters were optimized, and the two-lesion kinetics model (TLK) was used to calculate the cell survival rate, α, β, and relative biological effects (RBE) values under different LETd. Results LETd for carbon ions ranged from 24.30 to 310.355 keV/μm, corresponding to ion energies of 5.21-110.63 MeV/u. The DNA damage in A549 cells caused by the high LETd carbon ions was less repairable. The yield of single-strand breaks (SSB) decreased with increasing LETd, ranging from 118.428 to 160.401 Gy-1·Gbp-1. The yield of double-strand breaks (DSB) increased with increasing LETd, ranging from 7.235 to 10.435 Gy-1·Gbp-1. The simulated survival rate was consistent with the experimental data, indicating that the optimized parameters were suitable for simulating cell survival fractions under other carbon ion LETd conditions. In addition, the RBE values under different LETd were calculated using the linear-quadratic (LQ) model. Within the LETd range of 24.30-81.61 keV/μm, RBE increased with LETd, and the RBE values ranged from 1.01 to 1.89. Conclusions This study successfully used Geant4-DNA to simulate early DNA damage in A549 cells caused by carbon ion irradiation. By integrating the TLK model, the study linked early DNA damage repair processes to cell survival rates, successfully predicting cell survival rates, RBE, α, and β values under different LETd conditions. These findings provide a reference for molecular experiments on cellular damage and facilitate studies on biological effects in carbon ion radiotherapy. |
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