A cell-by-cell Monte Carlo simulation for assessing radiation-induced DNA double strand breaks

Brian HeeEun Lee*, C. K.Chris Wang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

This paper presents a cell-by-cell Monte Carlo simulation study that combines charged particle track structure data with an interphase cell nucleus model to quantify DNA double strand breaks (DSBs), spatial distribution of DSBs in a cell nucleus, and resulting potentially lethal or mutagenic events (PLMEs)between DSBs in close proximity. Cell nucleus is simulated according to the chromosome territory-interchromatin compartment (CT-IC)model in that chromatin content is unevenly distributed in chromatin domains (CDs)and IC with a chromatin compaction ratio of 22:1. A particle track structure coordinate (PTSC)library was first generated for each particle type, energy, and dose based on a large number of particle track data obtained by running the Monte Carlo track structure code Geant4-DNA. To assess the DNA DSBs of a cell for a specific particle type, energy, and dose, the corresponding PTSC was selected and “map overlaid” onto 960 unique cell nucleus data sets containing chromatin fiber (CF)locations. Clustering algorithm DBSCAN was next used to identify the clustered energy deposition events occurring inside the CF. These events were then converted to DNA DSBs using a probabilistic approach. The locations of the DSBs thus obtained were, in turn, used to calculate PLMEs within the cell nucleus that can result from DSB proximity and complexity. The results obtained from this simulation study are correctly correlated to the experimental data of DSB yield and the RBE-LET relationships for various types of charged particles and of various energies. The results show agreement with other published radiobiological models.

Original languageEnglish (US)
Pages (from-to)140-151
Number of pages12
JournalPhysica Medica
Volume62
DOIs
StatePublished - Jun 1 2019

Keywords

  • Chromatin domains
  • Chromatin fibers
  • DNA double strand breaks (DSB)
  • Monte Carlo method
  • Particle track structures
  • Relative biological effectiveness (RBE)

ASJC Scopus subject areas

  • Biophysics
  • Radiology Nuclear Medicine and imaging
  • Physics and Astronomy(all)

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