Ionising radiation induced DNA damage and subsequent biological responses to it depend on the radiation’s track-structure and its energy loss distribution pattern. To investigate the underlying biological mechanisms involved in such complex system, there is need of predicting biological response by integrated Monte Carlo (MC) simulations across physics, chemistry and biology. Hence, in this work, we have developed an application using the open source Geant4-DNA toolkit to propose a realistic “fully integrated” MC simulation to calculate both early DNA damage and subsequent biological responses with time. We had previously developed an application allowing simulations of radiation induced early DNA damage on a naked cell nucleus model. In the new version presented in this work, we have developed three additional important features: (1) modeling of a realistic cell geometry, (2) inclusion of a biological repair model, (3) refinement of DNA damage parameters for direct damage and indirect damage scoring. The simulation results are validated with experimental data in terms of Single Strand Break (SSB) yields for plasmid and Double Strand Break (DSB) yields for plasmid/human cell. In addition, the yields of indirect DSBs are compatible with the experimental scavengeable damage fraction. The simulation application also demonstrates agreement with experimental data of \(\gamma\)-H2AX yields for gamma ray irradiation. Using this application, it is now possible to predict biological response along time through track-structure MC simulations.

电离辐射诱导的DNA损伤及其后续的生物学反应取决于辐射的轨道结构及其能量损失分布模式。为了研究这种复杂系统中涉及的潜在生物学机制，需要通过跨物理，化学和生物学的综合蒙特卡罗（MC）模拟来预测生物学反应。因此，在这项工作中，我们开发了使用开源Geant4-DNA工具包的应用程序，提出了一个现实的“完全集成”的MC模拟，以计算早期DNA损伤和随后随时间的生物学反应。我们之前已经开发了一个应用程序，可以在裸细胞核模型上模拟辐射诱导的早期DNA损伤。在本文提出的新版本中，我们开发了三个附加的重要功能：（1）建模真实的细胞几何形状；（2）包含生物修复模型；（3）精炼DNA损伤参数以进行直接损伤和间接损伤评分。用质粒的单链断裂（SSB）产量和质粒/人细胞的双链断裂（DSB）产量的实验数据验证了模拟结果。此外，间接DSB的产量与实验可清除的损害分数兼容。仿真应用程序还证明了与实验数据的一致性。用质粒的单链断裂（SSB）产量和质粒/人细胞的双链断裂（DSB）产量的实验数据验证了模拟结果。此外，间接DSB的产量与实验可清除的损害分数兼容。仿真应用程序还证明了与实验数据的一致性。用质粒的单链断裂（SSB）产量和质粒/人细胞的双链断裂（DSB）产量的实验数据验证了模拟结果。此外，间接DSB的产量与实验可清除的损害分数兼容。仿真应用程序还证明了与实验数据的一致性。\（\ gamma \）- H2AX用于伽马射线辐照。使用此应用程序，现在可以通过轨道结构MC模拟来预测生物反应随时间的变化。