Quantification of DNA double-strand breaks using Geant4-DNA

Med Phys. 2019 Jan;46(1):405-413. doi: 10.1002/mp.13290. Epub 2018 Dec 7.

Abstract

Purpose: This study aims to standardize the simulation procedure in measuring DNA double-strand breaks (DSBs), by using advanced Monte Carlo toolkits, and newly introduced experimental methods for DNA DSB measurement.

Methods: For the experimental quantification of DNA DSB, an innovative DNA dosimeter was used to produce experimental data. GATE in combination with Geant4-DNA toolkit were exploited to simulate the experimental environment. The PDB4DNA example of Geant4-DNA was upgraded and investigated. Parameters of the simulation such energy threshold (ET) for a strand break and base pair threshold (BPT) for a DSB were evaluated, depending on the dose.

Results: Simulations resulted to minimum differentiation in comparison to experimental data for ET = 19 ± 1 eV and BPT = 10 bp, and high differentiation for ET<17.5 eV or ET>22.5 eV and BPT = 10 bp. There was also small differentiation for ET = 17.5 eV and BPT = 6 bp. Uncertainty has been kept lower than 3%.

Conclusions: This study includes first results on the quantification of DNA double-strand breaks. The energy spectrum of a LINAC was simulated and used for the first time to irradiate DNA molecules. Simulation outcome was validated on experimental data that were produced by a prototype DNA dosimeter.

Keywords: DNA dosimetry; DNA double-strand breaks; Geant4-DNA; Monte Carlo simulations; radiobiology.

MeSH terms

  • DNA / genetics*
  • DNA Breaks, Double-Stranded / radiation effects*
  • Monte Carlo Method*
  • Probability

Substances

  • DNA