| 韩旭,刘志强,张庆华,等.基于Geant4-DNA碳离子辐照A549细胞损伤模拟和存活率预测研究[J].中华放射医学与防护杂志,2026,46(3):246-255.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].Chin J Radiol Med Prot,2026,46(3):246-255 |
| 基于Geant4-DNA碳离子辐照A549细胞损伤模拟和存活率预测研究 |
| Prediction of DNA damage and cell survival rate after carbon ion irradiation for A549 cells using Geant4-DNA |
| 投稿时间：2024-11-06 |
| DOI：10.3760/cma.j.cn112271-20241106-00427 |
| 中文关键词: Geant4-DNA 碳离子 DNA损伤 细胞存活率预测 相对生物效能 |
| 英文关键词:Geant4-DNA Carbon ions DNA damage Cell survival rate prediction Relative biological effects (RBE) |
| 基金项目: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) |
| 作者 | 单位 | E-mail | | 韩旭 | 中国科学院近代物理研究所, 兰州 730000
兰州大学核科学与技术学院, 兰州 730000 | | | 刘志强 | 中国科学院近代物理研究所, 兰州 730000
兰州大学核科学与技术学院, 兰州 730000
兰州泰基离子技术有限公司, 兰州 730000 | | | 张庆华 | 中国科学院近代物理研究所, 兰州 730000
兰州大学核科学与技术学院, 兰州 730000 | | | 左子杰 | 中国科学院近代物理研究所, 兰州 730000
兰州大学核科学与技术学院, 兰州 730000 | | | 杨震 | 中国科学院近代物理研究所, 兰州 730000
甘肃中医药大学, 兰州 730000 | | | 罗宏涛 | 甘肃中医药大学, 兰州 730000 | | | 孙世龙 | 中国科学院近代物理研究所, 兰州 730000 | | | 张秋宁 | 中国科学院近代物理研究所, 兰州 730000
兰州泰基离子技术有限公司, 兰州 730000
中国科学院大学, 北京 100049 | zhangqn@impcas.ac.cn |
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| 中文摘要: |
| 目的 通过蒙特卡罗方法模拟碳离子辐照对A549细胞的早期DNA损伤以及预测细胞的存活率,建立一套实验数据驱动的碳离子辐照A549细胞生物学效应预测框架。方法 首先,基于蒙特卡罗工具Geant4-DNA,建立A549细胞及核DNA模型,并通过希尔伯特曲线迭代生成6.4 Gbp的分形染色质纤维结构。利用GATE模拟120.26 MeV/u单能碳离子束在不同水模体厚度下的能谱和剂量平均LET(LETd)分布。根据碳离子能谱信息,通过Geant4-DNA模拟不同LETd条件下的细胞辐照损伤。最后,基于细胞的实验数据对损伤修复参数进行优化,并使用双损伤动力学修复模型(TLK)计算不同LETd下的细胞存活率、α、β和相对生物效能(RBE)值。结果 碳离子能量5.21~110.63 MeV/u对应的LETd范围为24.30~310.355 keV/μm。碳离子的高LETd特性导致A549细胞DNA损伤较难修复,DNA单链断裂(SSB)产率随LETd升高而下降,损伤产率为118.428~160.401 Gy-1·Gbp-1,DNA双链断裂(DSB)产率随LETd升高而升高,损伤产率为7.235~10.435 Gy-1·Gbp-1。模拟得到的存活率与实验数据较为一致,表明优化后的参数适用于模拟其他碳离子LETd下的细胞存活分数。此外,通过LQ模型计算了不同LETd下的RBE,在24.30~81.61 keV/μm LETd范围内,RBE随LETd升高而升高,RBE值为1.01~1.89。结论 该研究采用Geant4-DNA对碳离子辐照A549细胞实验进行模拟,评估和量化了细胞早期碳离子辐照DNA损伤,并通过TLK模型将细胞早期DNA损伤修复过程与细胞存活率联系起来,成功预测不同LETd下细胞存活率、RBE、α和β值,为碳离子治疗非小细胞肺癌的生物学效应评估提供细胞特异性参考数据。 |
| 英文摘要: |
| 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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