Efficient cell-by-cell simulation of DNA double strand breaks, chromosome aberrations, and cell survival for low- and high-LET radiation particles using TOPAS-nBio and MEDRAS

The increasing sophistication of Monte Carlo (MC)-based simulations, such as TOPAS-nBio for radiation track structure and DNA damage, and MEDRAS-MC for subsequent DNA repair and cell survival, has ushered in an era of in-silico single-cell radiobiology. However, these simulations remain computationally prohibitive. In this study, we introduce a novel method that significantly accelerates the integrated simulation process for in-silico single-cell radiobiology. Our approach centers on pre-calculating and constructing a single-particle-track (SPT) standard DNA damage (SDD) data library using TOPAS-nBio. Each SPT-SDD data entry in this library records the positions of various DNA damage types (e.g., base damage, single-strand breaks, and double-strand breaks) produced by a single particle track. The comprehensive library contains a massive amount of SPT-SDD data entries, covering a broad range of particle energies. This data library functions as a look-up table, allowing for rapid assembly of DNA damage data for any desired dose level. This is achieved by randomly fetching and superimposing many SPT-SDD data entries from the pre-calculated library. The resulting "composite" SDD data file then serves as input for MEDRAS-MC to simulate and compute DNA damage outcomes, including chromosome aberrations and cell lethality for each individual cell. Furthermore, "timestamps" can be added to the superimposed data to account for dose rate effects. This work presents the first integrated Monte Carlo framework that bridges track-structure simulation (TOPAS-nBio) with mechanistic repair-misrepair modeling (MEDRAS-MC) to predict chromosome aberrations and cell lethality on a cell-by-cell basis. In this paper, we first describe this novel methodology and then apply it to compute radiation-induced outcomes for three previously reported in vitro experiments. These applications involve 280-kVp X-rays, protons, and alpha particles, covering a broad spectrum of linear energy transfer (LET). Finally, we compare our in silico results with experimental data and provide a detailed discussion of any observed discrepancies.