TOPAS-nBio simulation of temperature-dependent indirect DNA strand break yields

Abstract

Current Monte Carlo simulations of DNA damage have been reported only at ambient temperature. The aim of this work is to use TOPAS-nBio to simulate the yields of DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) produced in plasmids under low-LET irradiation incorporating the effect of the temperature changes in the environment. A new feature was implemented in TOPAS-nBio to incorporate reaction rates used in the simulation of the chemical stage of water radiolysis as a function of temperature. The implemented feature was verified by simulating temperature-dependent G-values of chemical species in liquid water from 20oC to 90oC. For radiobiology applications, temperature-dependent SSB and DSB yields were calculated from 0oC to 42oC, the range of available published measured data. For that, supercoiled DNA plasmid dissolved in aerated solutions containing EDTA irradiated by Cobalt-60 gamma-rays were simulated. TOPAS-nBio well reproduced published temperature-dependent G-values in liquid water and the yields of SSB and DSB for the temperature range considered. For strand break simulations, the model shows that the yield of SSB and DSB increased linearly with the temperature at a rate of (2.94±0.17)x10–10 Gy–1Da–1 oC–1 (R2=0.99) and (0.13±0.01)x10–10 Gy–1Da–1 oC–1 (R2=0.99), respectively. The extended capability of TOPAS-nBio is a complementary tool to simulate realistic conditions for a large range of environmental temperatures, allowing refined investigations of the biological effects of radiation.

Estimation of the relative biological effectiveness for double strand break induction of clinical kilovoltage beams using Monte Carlo simulations

“…The observations in this work reflect the results from a number of publications regarding the range of electrons in liquid water, as a function of electron energy 11,26–30 . In particular, it is evident that the majority of DNA damage is indirect which is in agreement with the results of Ramos et al., 31 who reported that the chemical processes are responsible for $$\approx 80\%$$ of the DNA damage.…”

“…The free radical probability of 0.4, DSB separation of 10 bp, and the ionization and damage energy thresholds (12.6 and 17.5 eV, respectively) adopted in our damage estimation algorithm are all based on values utilized in previously published works 23,36 . While some authors noted a dependence of DNA damage on temperature for TOPAS‐nBio simulations, 31 deviation from the default simulation parameters were beyond the scope of this work but should be investigated further.…”

Radical Production with Pulsed Beams: Understanding the Transition to FLASH

“…More recently, Mendez et al [ 60 ] conducted a simulation study on the temperature dependance of single (SSB) and double (DDB) indirect DNA strand breaks. Their results were compared to experimental data, showing a linear relation between the yield of SSB and DDB with temperature and dose.…”

Accessing radiation damage to biomolecules on the nanoscale by particle-scattering simulations

“…TOPAS-nBio allows for simulation of an extended list of chemical species such as O 2 (2.4), -O 2 (1.75), HO 2 (2.3) and -HO 2 (1.4) [40]. These models were successfully applied to predict temperature dependent DNA strand-break yields in plasmid DNA [127]. However, in general it has to be noted, that the simulation of the chemical stage with extended time scales up to the microseconds and short time steps is comparatively slower than the simulation of the scattering processes during the physical stage.…”