Modeling double-strand breaks from direct and indirect action in a complete human genome single cell Geant4 model

Xiandong Zhao, Ruirui Liu, Tianyu Zhao, Francisco J. Reynoso

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The aim of this work is to develop and validate a computational model to investigate direct and indirect DNA damage by directly quantifying DNA strand breaks. A detailed geometrical target model was created in the Monte Carlo toolkit Geant4 to represent the nucleus of a single human cell with complete human genome. A calculation framework to simulate double-strand breaks (DSBs) was implemented using this single cell model in the Geant4-DNA extension. A detailed ellipsoidal single cell model was implemented using a compacted DNA structure representing the fibroblast cell in the G0/G1 phase of the cycle using a total of 6 Gbp within the nucleus to represent the complete human genome. This geometry was developed from the publicly available Geant4-DNA example (wholeNuclearDNA), and modified to record DNA damage for both the physical and chemical stages. A clustering algorithm was implemented in the analysis process in order to quantify direct, indirect, and mixed DSBs. The model was validated against published experimental and computational results for DSB Gy−1Gbp−1 and the relative biological effectiveness (RBE) values for 250 kVp and Co-60 photons, as well as 2-100 MeV mono-energetic protons. A general agreement was observed over the whole simulated proton energy range, Co-60 beam, and 250 kVp in terms of the yield of DSB Gy−1Gbp−1 and RBE. The DSB yield was 8.0 ± 0.3 DSB Gy−1Gbp−1 for Co-60, and 9.2 ± 0.2 DSB Gy−1Gbp−1 for 250 kVp, and between 11.1 ± 0.9 and 8.1 ± 0.5 DSB Gy−1Gbp−1 for 2-100 MeV protons. The results also show mixed DSBs composed of direct and indirect SSBs make up more than half of the total DSBs. The results presented indicate that the current model reliably predicts the DSB yield and RBE for proton and photon irradiations, and allows for the detailed computational investigation of direct and indirect effects in DNA damage.

Original languageEnglish
Article numberA10
JournalBiomedical Physics and Engineering Express
Volume6
Issue number6
DOIs
StatePublished - Nov 2020

Keywords

  • DBSCAN
  • DNA damage
  • DNA model
  • Geant4-DNA
  • Radiation therapy

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