scholarly journals Can We Assess Early DNA Damage at the Molecular Scale by Radiation Track Structure Simulations? A Tetranucleosome Scenario in Geant4-DNA

2020 ◽  
Vol 8 ◽  
Author(s):  
Lorenzo Petrolli ◽  
Francesco Tommasino ◽  
Emanuele Scifoni ◽  
Gianluca Lattanzi
Keyword(s):  
Dna Damage ◽  
Track Structure ◽  
Molecular Scale

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

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6046
Author(s):  
Dousatsu Sakata ◽  
Masao Suzuki ◽  
Ryoichi Hirayama ◽  
Yasushi Abe ◽  
Masayuki Muramatsu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radiation Treatment ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Model Parameters ◽  
Track Structure ◽  
V79 Cells ◽  
Damage Repair ◽  
Kinetics Of ◽  
Mev Protons

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.

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

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Dousatsu Sakata ◽  
Oleg Belov ◽  
Marie-Claude Bordage ◽  
Dimitris Emfietzoglou ◽  
Susanna Guatelli ◽  
...  
Keyword(s):  
Experimental Data ◽  
Dna Damage ◽  
Monte Carlo ◽  
Biological Response ◽  
Strand Break ◽  
Track Structure ◽  
Single Strand Break ◽  
Fully Integrated ◽  
Biological Responses ◽  
Radiation Induced

AbstractIonising radiation induced DNA damage and subsequent biological responses to it 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. 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. We had previously developed an application allowing simulations of radiation induced early DNA damage on a naked cell nucleus model. In the new version presented in this work, we have developed three additional important features: (1) modeling of a realistic cell geometry, (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 Single Strand Break (SSB) yields for plasmid and Double Strand Break (DSB) yields for plasmid/human cell. In addition, the yields of indirect DSBs are compatible with the experimental scavengeable damage fraction. The simulation application also demonstrates agreement with experimental data of $$\gamma$$ γ -H2AX yields for gamma ray irradiation. Using this application, it is now possible to predict biological response along time through track-structure MC simulations.

Quantitative modelling of DNA damage using Monte Carlo track structure method

1999 ◽  
Vol 38 (1) ◽  
pp. 31-38 ◽  
Author(s):  
H. Nikjoo ◽  
P. O'Neill ◽  
M. Terrissol ◽  
D. T. Goodhead
Keyword(s):  
Dna Damage ◽  
Monte Carlo ◽  
Track Structure ◽  
Quantitative Modelling

scholarly journals Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Pavel Kundrát ◽  
Werner Friedland ◽  
Janine Becker ◽  
Markus Eidemüller ◽  
Andrea Ottolenghi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radiation Transport ◽  
Biological Effects ◽  
Spatial Scales ◽  
Track Structure ◽  
Monte Carlo Code ◽  
Strand Breaks ◽  
Light Ions ◽  
Analytical Formulas ◽  
Mixed Radiation Field

Abstract Track structure based simulations valuably complement experimental research on biological effects of ionizing radiation. They provide information at the highest level of detail on initial DNA damage induced by diverse types of radiation. Simulations with the biophysical Monte Carlo code PARTRAC have been used for testing working hypotheses on radiation action mechanisms, for benchmarking other damage codes and as input for modelling subsequent biological processes. To facilitate such applications and in particular to enable extending the simulations to mixed radiation field conditions, we present analytical formulas that capture PARTRAC simulation results on DNA single- and double-strand breaks and their clusters induced in cells irradiated by ions ranging from hydrogen to neon at energies from 0.5 GeV/u down to their stopping. These functions offer a means by which radiation transport codes at the macroscopic scale could easily be extended to predict biological effects, exploiting a large database of results from micro-/nanoscale simulations, without having to deal with the coupling of spatial scales and running full track-structure calculations.

From track structure to stochastic chemistry and DNA damage: Microdosimetric perspective

2000 ◽  
Vol 80 (3) ◽  
pp. 327-340 ◽  
Author(s):  
Marco Zaider ◽  
Albert Y. C. Fung ◽  
Jingdong Li ◽  
J. Ladik
Keyword(s):  
Dna Damage ◽  
Track Structure

On the consistency of Monte Carlo track structure DNA damage simulations

2014 ◽  
Vol 41 (12) ◽  
pp. 121708 ◽  
Author(s):  
Piotr Pater ◽  
Jan Seuntjens ◽  
Issam El Naqa ◽  
Mario A. Bernal
Keyword(s):  
Dna Damage ◽  
Monte Carlo ◽  
Track Structure

Can Monte Carlo track structure codes reveal reaction mechanism in DNA damage and improve radiation therapy?

2008 ◽  
Vol 77 (10-12) ◽  
pp. 1270-1279 ◽  
Author(s):  
Hooshang Nikjoo ◽  
Dimitris Emfietzoglou ◽  
Ritsuko Watanabe ◽  
Shuzo Uehara
Keyword(s):  
Dna Damage ◽  
Monte Carlo ◽  
Radiation Therapy ◽  
Reaction Mechanism ◽  
Track Structure

scholarly journals Performance Evaluation for Repair of Hsgc-c5 Carcinoma Cell Using geant4-Dna

2021 ◽  
Author(s):  
Dousatsu Sakata ◽  
Masao Suzuki ◽  
Ryoichi Hirayama ◽  
Yasushi Abe ◽  
Masayuki Muramatsu ◽  
...  
Keyword(s):  
Dna Damage ◽  
Radiation Treatment ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Model Parameters ◽  
Track Structure ◽  
Experimental Measurements ◽  
V79 Cells ◽  
Damage Repair ◽  
Kinetics Of

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 the different cell lines. Thus, we extended the Geant4-DNA application with an updated 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-C5s cells. Concerning fast- and slow-DNA rejoining, the TLK model parameters were adequately optimized with the simulated initial DNA damage. Using the optimized TLK model, the Geant4-DNA simulation is now able to predict cell survival and DNA-rejoining kinetics for HSGc-C5s cells.

scholarly journals A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields

2020 ◽  
Vol 21 (5) ◽  
pp. 1701 ◽  
Author(s):  
Yusuke Matsuya ◽  
Toshiaki Nakano ◽  
Takeshi Kai ◽  
Naoya Shikazono ◽  
Ken Akamatsu ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Dna Damage ◽  
Detection Efficiency ◽  
Complex Form ◽  
Track Structure ◽  
Computational Results ◽  
X Ray ◽  
Electron Track ◽  
Experimental Complex

Complex DNA damage, defined as at least two vicinal lesions within 10–20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations.

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