title: On the consistency of Monte Carlo track structure DNA damage simulations.
abstract: OBJECTIVE
  Monte Carlo track structures (MCTS) simulations have been recognized as useful tools for radiobiological modeling. However, the authors noticed several issues regarding the consistency of reported data. Therefore, in this work, they analyze the impact of various user defined parameters on simulated direct DNA damage yields. In addition, they draw attention to discrepancies in published literature in DNA strand break (SB) yields and selected methodologies.
  
  
  METHODS
  The MCTS code Geant4-DNA was used to compare radial dose profiles in a nanometer-scale region of interest (ROI) for photon sources of varying sizes and energies. Then, electron tracks of 0.28 keV-220 keV were superimposed on a geometric DNA model composed of 2.7 × 10(6) nucleosomes, and SBs were simulated according to four definitions based on energy deposits or energy transfers in DNA strand targets compared to a threshold energy ETH. The SB frequencies and complexities in nucleosomes as a function of incident electron energies were obtained. SBs were classified into higher order clusters such as single and double strand breaks (SSBs and DSBs) based on inter-SB distances and on the number of affected strands.
  
  
  RESULTS
  Comparisons of different nonuniform dose distributions lacking charged particle equilibrium may lead to erroneous conclusions regarding the effect of energy on relative biological effectiveness. The energy transfer-based SB definitions give similar SB yields as the one based on energy deposit when ETH ≈ 10.79 eV, but deviate significantly for higher ETH values. Between 30 and 40 nucleosomes/Gy show at least one SB in the ROI. The number of nucleosomes that present a complex damage pattern of more than 2 SBs and the degree of complexity of the damage in these nucleosomes diminish as the incident electron energy increases. DNA damage classification into SSB and DSB is highly dependent on the definitions of these higher order structures and their implementations. The authors' show that, for the four studied models, different yields are expected by up to 54% for SSBs and by up to 32% for DSBs, as a function of the incident electrons energy and of the models being compared.
  
  
  CONCLUSIONS
  MCTS simulations allow to compare direct DNA damage types and complexities induced by ionizing radiation. However, simulation results depend to a large degree on user-defined parameters, definitions, and algorithms such as: DNA model, dose distribution, SB definition, and the DNA damage clustering algorithm. These interdependencies should be well controlled during the simulations and explicitly reported when comparing results to experiments or calculations.
authors.affiliation: McGill University, Montreal, Quebec H3G 1A4, Canada.
authors.forename: Piotr
authors.initials: P
authors.lastname: Pater
authors.affiliation: McGill University, Montreal, Quebec H3G 1A4, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Seuntjens
authors.affiliation: McGill University, Montreal, Quebec H3G 1A4, Canada.
authors.forename: Issam
authors.initials: I
authors.lastname: El Naqa
authors.affiliation: Instituto de Fisica Gleb Wataghin, Universidade Estadual de Campinas, Campinas 13083-859, Brazil.
authors.forename: Mario A
authors.initials: MA
authors.lastname: Bernal
mesh_terms: D000465:Algorithms; D055592:Biophysical Phenomena; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded; D053904:DNA Breaks, Single-Stranded; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004583:Electrons; D008956:Models, Chemical; D015394:Molecular Structure; D009010:Monte Carlo Method; D009707:Nucleosomes / Q000737:chemistry / Q000528:radiation effects; D017785:Photons; D012062:Relative Biological Effectiveness
chemical_list: D009707:Nucleosomes; D004247:DNA