Monte Carlo simulation of chemistry following radiolysis with TOPAS-nBio

Abstract

Simulation of water radiolysis and the subsequent chemistry provides important information on the effect of ionizing radiation on biological material. The Geant4 Monte Carlo toolkit has added chemical processes via the Geant4-DNA project. The TOPAS tool simplifies the modeling of complex radiotherapy applications with Geant4 without requiring advanced computational skills, extending the pool of users. Thus, a new extension to TOPAS, TOPAS-nBio, is under development to facilitate the configuration of track-structure simulations as well as water radiolysis simulations with Geant4-DNA for radiobiological studies. In this work, radiolysis simulations were implemented in TOPAS-nBio. Users may now easily add chemical species and their reactions, and set parameters including branching ratios, dissociation schemes, diffusion coefficients, and reaction rates. In addition, parameters for the chemical stage were re-evaluated and updated from those used by default in Geant4-DNA to improve the accuracy of chemical yields. Simulation results of time-dependent and LET-dependent primary yields G (chemical species per 100 eV deposited) produced at neutral pH and 25 °C by short track-segments of charged particles were compared to published measurements. The LET range was 0.05-230 keV µm. The calculated G values for electrons satisfied the material balance equation within 0.3%, similar for protons albeit with long calculation time. A smaller geometry was used to speed up proton and alpha simulations, with an acceptable difference in the balance equation of 1.3%. Available experimental data of time-dependent G-values for [Formula: see text] agreed with simulated results within 7% ± 8% over the entire time range; for [Formula: see text] over the full time range within 3% ± 4%; for HO from 49% ± 7% at earliest stages and 3% ± 12% at saturation. For the LET-dependent G, the mean ratios to the experimental data were 1.11 ± 0.98, 1.21 ± 1.11, 1.05 ± 0.52, 1.23 ± 0.59 and 1.49 ± 0.63 (1 standard deviation) for [Formula: see text], [Formula: see text], H, HO and [Formula: see text], respectively. In conclusion, radiolysis and subsequent chemistry with Geant4-DNA has been successfully incorporated in TOPAS-nBio. Results are in reasonable agreement with published measured and simulated data.

A new open‐source GPU‐based microscopic Monte Carlo simulation tool for the calculations of DNA damages caused by ionizing radiation — Part II: sensitivity and uncertainty analysis

“…While conducting this study, we noticed that the research group at the Massachusetts General Hospital (MGH) performed a similar research to investigate the impacts of different simulation parameters on DNA damages in the context of proton irradiation . They studied the effects of variation in physics model (G4EmDNAphysics opt2, opt4, and opt6), chemical stage model (TsEmchemistry model and G4Emchemistry model), energy model (threshold and linear‐probability damage models), chemical stage length (1, 2.5, 10 ns), and hydroxyl damage probability (0.4, 0.65) on SBs and DSBs under different linear energy transfer (LET) conditions. Our result generally agreed with theirs.…”

Cellular Response to Proton Irradiation: A Simulation Study with TOPAS-nBio

“…The TOPAS-nBio extension is an advanced, yet userfriendly, Monte Carlo track structure simulation tool based on Geant4-DNA (9,10). It offers an extensive library of advanced biological geometries ranging from the micrometer scale (e.g., cells and organelles) down to the nanometer scale (e.g., DNA molecules and proteins) (38) to support simulation studies at the cellular and subcellular levels with the goal of furthering our understanding of radiobiological effects at the DNA (nanometer) scale (38)(39)(40). A full nucleus model was developed based on folding chromatin fibers in a fractal as indicated by Lieberman-Aiden et al (41); the chromatin conformation is consistent with a knot-free fractal globule at the megabase scale.…”

“…The TsEmDNAChemistry model was validated by calculating time-dependent G values (number of molecular species per 100 eV of energy deposited) for electrons, protons and a particles for a wide range of LET (0.05-230 keV/lm). All details have been provided elsewhere (40).…”

Analysis in the generation of reactive oxygen species through the interaction between the secondary radiation of the compound system (cisplatin and silica nanoparticle) and intracellular water

“…These processes can generate different chemical species depending on the physical process, considering up to five internal atomic orbital levels of the atoms/molecules where the radiation occurs. In the chemical part of the simulation of water radiolysis (from 1 ps -1 µs), the Brownian Movement Theory is used, which requires diffusion constants [8]. For this study, secondary radiation is used, that occurs in the platinum atom, specifically the Auger electrons generated by applying external radiation (electrons with an energy of 5 keV) to the physical system shown in Fig.…”

“…This work simulates the production of reactive oxygen species generated when Auger electrons react with intracellular water. To do this, the TOPAS-nBio [8][9][10] code was used, which was efficient in quantifying the amount of ROS as a function of time and the energy spectrum of the Auger electrons. The reactive species e aq¯s olvated electron, OH * hydroxyl radical, H Hydrogen,…”