A simulation approach for determining the spectrum of DNA damage induced by protons

Abstract

To study the molecular damage induced in the form of single-strand and double-strand breaks by ionizing radiation at the DNA level, the Geant4-DNA Monte Carlo simulation code for complete transportation of primary protons and other secondary particles in liquid water has been employed in this work. To this aim, a B-DNA model and a thorough classification of the complexity of the DNA damage were used. Strand breaks were assumed to have primarily originated by direct physical interactions via energy depositions, assuming a threshold energy of 17.5 eV, or indirect chemical reactions of hydroxyl radicals, assuming a probability of 0.13. The simulation results on the complexity and frequency of various damages are computed for proton energies of 0.5-20 MeV. The yield results for a cell (Gy cell) are presented, assuming 22 chromosomes per cell and a mean number of 245 Mbp per chromosome. The results show that for proton energies below 2 MeV, more than 50% of the energy depositions within the DNA volume resulted in strand breaks. For double-strand breaks (DSBs), there is considerable sensitivity of DSB frequency to the proton energy. A comparison of DSB frequencies predicted by different simulations and experiments is presented as a function of proton linear energy transfer (LET). We show that our yield results (Gy Gbp) are generally comparable with various experimental data and there seems to be a better agreement between our results and a number of experimental studies when compared to other simulations.

Cellular Response to Proton Irradiation: A Simulation Study with TOPAS-nBio

“…Following previous studies (43,(52)(53)(54), the chemical stage lasted up to 1 ns to mimic scavenging properties within the cell. To model the indirect DNA damages, all radiolysis products were simulated; however, only interactions between hydroxyl radicals ( OH) and the DNA backbone were assumed to induce indirect strand breaks (SB indir ) with a reaction probability of 0.4 (42,47).…”

A parameter sensitivity study for simulating DNA damage after proton irradiation using TOPAS-nBio

“…Furthermore, different studies adopted different parameter values, which could also significantly alter simulation results. For instance, some studies (Mokari et al, 2018;Lampe et al, 2018b;Meylan et al, 2017;Nikjoo et al, 2001) assumed that a direct strand break (SB) is formed with a fixed threshold of 17.5 eV, i.e., a direct SB will be formed if the accumulated energy deposition within one sugar phosphate or hydration shell exceeds this threshold. In contrast, other studies (Friedland et al, 2017;Friedland et al, 2011;Friedland et al, 2003;Sakata et al, 2019) used a linear acceptance threshold ranging from 5 to 37.5 eV, i.e., the probability to form a direct SB linearly increases from 0 when less than 5 eV energy deposition was accumulated to 1 when more than 37.5 eV energy deposition was accumulated in the target DNA volume.…”

“…However, the uncertainties due to the chosen DNA geometry was not considered in this work. •OH damage probability (c) Direct damage threshold (Nikjoo et al, 2001) PITS --1 ns 0.13 (a) 17.5 eV (Friedland et al, 2017) PARTRAC --100 ns 0.65 (b) 5-37.5 eV (Friedland et al, 2011) PARTRAC --2.5 ns 0.65 (b) 5-37.5 eV (Friedland et al, 2003) PARTRAC --10 ns 0.13 (a) 5-37.5 eV (Sakata et al, 2019) Geant4-DNA option4 2.5 ns 0.4 (b) 5-37.5 eV (Mokari et al, 2018) Geant4-DNA default 1 ns 0.65 (b) 17.5 eV (Lampe et al, 2018a) Geant4-DNA option4 1 ns 0.4 (b) 17.5 eV (Meylan et al, 2017) Geant4-DNA default 2.5 ns 0.4 (b) 17.5 eV (a). Defined between •OH and whole DNA volume (b).…”

DNA damage and microdosimetry for carbon ions: Track structure simulations as the key to quantitative modeling of radiation‐induced damage

“…The bottom panel shows the ratio of our SSB and DSB yields, in comparison with PARTRAC and Geant4‐DNA proton results of Sakata et al 55 . as well as the results extracted from our previous studies for protons 16 and alpha particles 17 …”