摘要目的:模拟V79细胞在碳离子不同剂量平均LET（dose-averaged LET，LET d）下的细胞核DNA早期损伤和修复过程，并评估其对细胞存活率的影响。 方法:首先，基于Geant4-DNA建立V79细胞的细胞质、细胞核、以及基于分形几何结构排列的细胞核DNA模型。然后使用Geant4-DNA中三种物理模型（G4EmDNAPhysics_option2、_option4、_option6）模拟不同LET d的碳离子与细胞的相互作用，得到碳离子辐照下的细胞核DNA直接损伤和间接损伤产额。最后利用双损伤动力学模型（Two-Lesion Kinetics，TLK）计算细胞存活率，并以细胞辐射生物实验数据为依据，优化TLK模型参数。细胞入射前不同能量的碳离子LET d由GATE模拟可得。 结果:随着碳离子LET d的增加，DNA单链断裂（single--strand breaks，SSB）产额下降，DNA双链断裂（double-strand breaks，DSB）产额上升，表明高LET d碳离子更容易导致细胞死亡。通过对TLK模型损伤修复参数的优化，模拟得到其他LET d下的细胞存活分数与实验数据吻合程度较高，且模拟α值与实验α值平均相差1.555% ±2.464%，模拟 β值与文献 β 平均相差 1.468%±0.462%，模拟RBE值与实验RBE平均相差0.180±0.083。 结论:本研究通过模拟和实验验证，建立了可靠的V79细胞模型，能够预测碳离子不同LET d下的细胞存活率、α、β以及RBE值，为碳离子放射治疗的生物学效应研究提供了重要参考。尽管模型存在一定的局限性，如未能体现细胞周期的影响，但模拟结果与实验数据的一致性验证了模型的可靠性。

abstractsObjective:This study aims to simulate the early DNA damage and repair processes in V79 cells under different dose-averaged linear energy transfer (LET d) of carbon ions and to evaluate its impact on cell survival rates. Methods:First, a model of cytoplasm, nucleus, and nucleus DNA arranged based on fractal geometry was established for V79 cells using GEANT4-DNA. Then, the interaction between carbon ions with varying LET d and the cells was simulated using three physical models in Geant4-DNA (G4EmDNAPhysics_option2, _option4, and _option6), leading to the assessment of direct and indirect DNA damage yields under carbon ion irradiation. Finally, the cell survival rate was calculated using the Two-Lesion Kinetics (TLK) model, with the model parameters optimized based on experimental data from cellular radiation biology. LET d of carbon ions with different energies before cell entry was obtained through GATE simulations. Results:With the increase in the LETd of carbon ions, the yield of DNA single-strand breaks (SSBs) decreased, while the yield of DNA double-strand breaks (DSBs) increased, indicating that high-LETd carbon ions are more effective at inducing cell death. After optimizing the damage repair parameters of the TLK model, the simulated survival fractions at various LETd showed good agreement with the experimental data. The discrepancies between the simulations and experiments were minimal, with an average difference of 1.555% ± 2.464% for the α parameter, 1.468% ± 0.462% for the β parameter, and 0.180 ± 0.083 for the relative biological effectiveness (RBE) values.Conclusions:Through simulation and experimental validation, this study established a reliable V79 cell model that can predict cell survival rates, α, β, and RBE values under different LET d of carbon ions. This provides important references for the biological effects of carbon ion radiotherapy. Although the model has certain limitations, such as not accounting for cell cycle effects, the consistency of the simulation results with experimental data verifies the model's reliability.