Fully integrated Monte Carlo simulation for evaluating radiation induced DNA damage and subsequent repair using Geant4-DNA

1. Introduction Ionising radiation induced DNA damage and subsequent biological responses 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. Typically, modeling of survival fraction and/or kinetics of repair proteins attracts interests of researchers in the fields of radiobiology including medical physics. 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. 2. Materials and Methods We had previously developed an application allowing simulations of radiation induced early DNA damage on a naked cell nucleus model and its sub-components model (shown in top panels of Fig.1) [1]. In the new version presented in this work [2], we have developed three additional important features: (1) modeling of a realistic cell geometry including cytoplasm and the materials surrounding irradiated cells (shown in bottom panels of Fig.1), (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 Double Strand Break (DSB) yields for human fibroblast cell as well as yield of accumulated γ-H2AX. In addition, the yields of indirect DSBs are compatible with the experimental scavengeable damage fraction. 3. Results and Discussion The simulated quantities are showing good agreements with the reference experimental quantities. For instance, as shown in Fig.2, the simulation application also demonstrates agreement with experimental data of γ-H2AX yields for gamma ray irradiation. 4. Conclusion As a new important step for radiobiological simulation using Geant4-DNA, the first fully integrated simulation chain has been developed across the physical, chemical and biological stages of cellular radiation action in a single application. The application is validated with the reference experimental results.
第121回 日本医学物理学会学術大会