Abstract
Simple SummaryTo evaluate the repair performance of HSGc-C5 carcinoma cell against radiation-induced DNA damage, a Geant4-DNA application for radiobiological research was extended by using newly measured experimental data acquired in this study. Concerning fast- and slow-DNA rejoining, the two-lesion kinetics (TLK) model parameters were adequately optimized (the repair speeds of each process were reasonably close to the DNA rejoining speed of the nonhomologous end-joining and homologous recombination pathways). The lethality probabilities of the DNA damage induced by complex double strand breaks (DSBs) and binary repair were approximately and , respectively. Using the optimized repair parameters, the Geant4-DNA simulation was able to predict the cell surviving fraction (SF) and the DNA repair kinetics.Track-structure Monte Carlo simulations are useful tools to evaluate initial DNA damage induced by irradiation. In the previous study, we have developed a Gean4-DNA-based application to estimate the cell surviving fraction of V79 cells after irradiation, bridging the gap between the initial DNA damage and the DNA rejoining kinetics by means of the two-lesion kinetics (TLK) model. However, since the DNA repair performance depends on cell line, the same model parameters cannot be used for different cell lines. Thus, we extended the Geant4-DNA application with a TLK model for the evaluation of DNA damage repair performance in HSGc-C5 carcinoma cells which are typically used for evaluating proton/carbon radiation treatment effects. For this evaluation, we also performed experimental measurements for cell surviving fractions and DNA rejoining kinetics of the HSGc-C5 cells irradiated by 70 MeV protons at the cyclotron facility at the National Institutes for Quantum and Radiological Science and Technology (QST). Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. The optimized DNA rejoining speeds were reasonably agreed with the experimental DNA rejoining speeds. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5 cells.
Highlights
Radiation treatment is one of the most widely used therapeutic techniques for cancer treatment aiming at depriving tumor cells of their reproductive potential [1]
This study is comprised of two parts: The first part is an experimental study to measure cell surviving fractions (SFs) and DNA rejoining kinetics as the reference data for the optimization of the two-lesion kinetics (TLK) model parameters of HSGc-C5
We considered that all simple double-strand breaks (DSBs) are repaired by the fast-repair process, and all complex DSBs are repaired by the slow-repair process
Summary
Radiation treatment is one of the most widely used therapeutic techniques for cancer treatment aiming at depriving tumor cells of their reproductive potential [1]. Radiation-induced crucial DNA damage represented by double-strand breaks (DSBs) can be a cause of reproductive cell death [1,2]. Because of the experimental requirements, it is difficult to directly observe and quantify the details of such microscopic lesions. Due to this difficulty, indirect measurements of features related to initial DNA damage, such as physical disconnection of DNA fiber [3,4], chromosomal aberrations [5], and phosphorylated H2AX as a marker for DSBs [6,7,8], have been attempted to further investigate radiation-induced. Many MC codes have achieved successful outcomes for quantitative investigation of radiation-induced initial DNA damage within cellular domains and subcellular biological components [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]
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