Performance Evaluation for Repair of HSGc-C5 Carcinoma Cell Using Geant4-DNA

Abstract

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.

Simulation of DNA damage using Geant4‐DNA: an overview of the “molecularDNA” example application

“…The results of this simulation study were compared with both experimental [46][47][48][49][50][51][52][53][54][55] and other simulation data, 28,30,31,33 in terms of calculation of the number of strand breaks (SB) and of direct/indirect damage. To generate a direct DNA damage lesion, the energy deposited during a physical interaction should be closer than 3.5 Å to a DNA base (R dir ).…”

“…To validate the newly developed algorithm, the present study implemented the same parameter values adopted by Sakata et al 31 Additionally, L 1 (t) is the number of lesions per cell in the fastrepair process at a given time t after the beginning of the irradiation procedure. L 2 (t) is the number of lesions per cell in the slow-repair process at a given time t. L f (t) is the number of lethal lesions that may lead to cell death at time t. D(t) is the dose rate, Y is the size of the cell in Giga bp (Gbps).…”

“…This public version of "molecularDNA", based on a non-public prototype by Lampe et al, 26,27 has been significantly upgraded from its previous development iterations. [28][29][30][31][32][33][34] In particular, it includes the new chemistry model (Synchronous Independent Reaction Time model, socalled "IRT-sync"), 35 the "G4EmDNAChemistry_option3" Geant4-DNA chemistry list based on Plante and Devroye, 36 as well as an upgrade of computational tools to estimate DNA damage response (DDR), such as repair kinetics and survival probability of cells. In addition, in this study, simulation results are benchmarked against results available in the literature.…”

A double‐strand‐break model for the relative biological effectiveness of electrons based on ionization clustering

“…Since for ions their biological action is mainly mediated by secondary electrons, these aspects are also important for modeling the biological effects of ion beam radiation, where they are considered in different levels of detail. Models aiming at the explanation of radiation effects on a mechanistic basis, for example, Monte Carlo models based on the precise structural organization of the DNA molecule on an atomic level, take into account these processes in detail 45–50 . However, they are very time consuming and are thus not suitable for certain applications, for example, in biologically optimized treatment planning.…”

“…Models aiming at the explanation of radiation effects on a mechanistic basis, for example, Monte Carlo models based on the precise structural organization of the DNA molecule on an atomic level, take into account these processes in detail. [45][46][47][48][49][50] However, they are very time consuming and are thus not suitable for certain applications, for example, in biologically optimized treatment planning. More empirical models such as frequently used implementations of the microdosimetric kinetic model (MKM) 51,52 and the local effect model (LEM) [53][54][55] circumvent this problem by predicting the effects of ion beams with simplified representations of cell nuclei and amorphous track structure representations.…”