Monte Carlo Simulation of the Production of Short DNA Fragments by Low-Linear Energy Transfer Radiation Using Higher-Order DNA Models

Abstract

A realistic DNA target model has been developed and implemented in the biophysical simulation code PARTRAC. It describes five levels of the B-DNA structure (nucleotides, DNA helices, nucleosomes, chromatin fiber structure and chromatin fiber loops) on an atomic level for the whole genome inside a mammalian cell nucleus. The model is capable of describing regular solenoidal, crossed-linker or zigzag structures as well as repeating stochastic arrangements of nucleosomes in the chromatin fiber. Electron tracks resulting from monoenergetic electrons with energies up to 100 keV and from 220 kVp X rays, starting at random positions in the cell, were superimposed on four DNA target models with different chromatin fiber structures. The yields of SSBs, DSBs and short single- and double-stranded DNA fragments were determined from spatial coincidences with strand atoms. Two parameters of the model-the energy necessary to create an SSB and the distance between two breaks that would be scored as a DSB-were adapted to equate simulated and measured strand break yields after X irradiation of human fibroblast cells. The integral fractions of short single- and double-stranded fragments were rather similar for all condensed chromatin fiber structures; they agreed with experimental data for DNA fragments below 2 kbp. The simulated fragment size distributions in the range from 0.1 to 1.5 kbp reflected the fiber structure irrespective of strandedness or electron energy. The distributions using a stochastic arrangement of nucleosomes in the chromatin fiber were found to be in better accordance with experimental data than those obtained with regular fiber structures.

Electron emission from amorphous solid water after proton impact: Benchmarking PTra and Geant4 track structure Monte Carlo simulations

“…In the simulation, the particles are transported until their energy falls below a certain limit, generally given by the lower limit of the interaction cross section data, and are then assumed to deposit their remaining energy at the position of their last interaction. Detailed descriptions regarding the principle of track structure simulations can be found in Friedland et al (1998), Grosswendt (2002), Zaider et al (1994) as well as in Nikjoo et al (2006), where also a comprehensive overview of existing codes is provided.…”

“…Monte Carlo simulations of the track structure of ionising radiation in water medium are traditionally applied to estimate direct DNA damage (Francis et al, 2011;Friedland et al, 1998;Grosswendt, 2002;Nikjoo et al, 2006). Clustered damage occurring on short segments of the DNA (length of a few nanometres) is assumed to be the actuator for subsequent radiobiological effects, such as carcinogenesis or cell death (Goodhead, 2006;Khanna and Jackson, 2001).…”

Influence of the chromatin density on the number of direct clustered damages calculated for proton and alpha irradiations using a Monte Carlo code

“…The relative volume occupied by DNA is then 1.43% for the endothelium nucleus and 0.42% for the fibroblast. The geometry of the total DNA molecule (about 6 Gbp) within the cell nucleus is divided in five compaction levels based on the PARTRAC geometrical model [9,10]: DNA double helix, nucleosomes, chromatin fiber, chromatin fiber loop and chromosome territories.…”

Ionization cross section data of nitrogen, methane, and propane for light ions and electrons and their suitability for use in track structure simulations

“…Particle-track simulation codes can, however, be benchmarked with measured data by modeling a micro-or nanodosimetric experiment, which is performed in millimeter-sized volumes of low-pressure gas [7,8]. To simulate the particle track, the history of an incident projectile is followed interaction by interaction through the medium [3,8,9]. For such detailed simulations, the cross sections for the physical interactions of the incident particles with the molecules comprising the medium are essential input data.…”

“…Micro-and nanodosimetric approaches have been under development for several years [1][2][3][4][5][6] as a means to characterize the track structure of ionizing radiation. This characterization is particularly important for an estimation of initial radiationinduced biological effects on the microscopic scale.…”