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Objective . To study the effect of dose-rate in the time evolution of chemical yields produced in pure water versus a cellular-like environment for FLASH radiotherapy research. Approach. A version of TOPAS-nBio with Tau-Leaping algorithm was used to simulate the homogenous chemistry stage of water radiolysis using three chemical models: (1) liquid water model that considered scavenging of e aq - , H • by dissolved oxygen; (2) Michaels & Hunt model that considered scavenging of • OH, e aq ‒ , and H • by biomolecules existing in cellular environment; (3) Wardman model that considered model 2) and the non-enzymatic antioxidant glutathione (GSH). H 2 O 2 concentrations at conventional and FLASH dose-rates were compared with published measurements. Model 3) was used to estimate DNA single-strand break (SSB) yields and compared with published data. SSBs were estimated from simulated yields of DNA hydrogen abstraction and attenuation factors to account for the scavenging capacity of the medium. The simulation setup consisted of monoenergetic protons (100 MeV) delivered in pulses at conventional (0.2857Gy s -1 ) and FLASH (500Gy s -1 ) dose rates. Dose varied from 5-20 Gy, and oxygen concentration from 10 µ M-1 mM. Main Results. At the steady state, for model (1), H 2 O 2 concentration differed by 81.5%± 4.0% between FLASH and conventional dose-rates. For models (2) and (3) the differences were within 8.0%± 4.8%, and calculated SSB yields agreed with published data within 3.8%± 1.2%. A maximum oxygen concentration difference of 60% and 50% for models (2) and (3) between conventional and FLASH dose-rates was found between 2 × 10 6 and 9 × 10 13 ps for 20 Gy of absorbed dose. Significance. The findings highlight the importance of developing more advanced cellular models to account for both the chemical and biological factors that comprise the FLASH effect. It was found that differences between pure water and cellular environment models were significant and extrapolating results between the two should be avoided. Observed differences call for further experimental investigation., (© 2025 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

To better assess the potential biological consequences of diagnostic x-rays and selected gamma-emitting radioisotopes used in brachytherapy, we used the PENELOPE Monte Carlo radiation transport code to estimate the spectrum of initial electrons produced by photons in single cells and in an irradiation geometry similar to those used in cell culture experiments. We then combined estimates of the initial spectrum of electrons from PENELOPE with DNA damage yields for monoenergetic electrons from the fast Monte Carlo damage simulation (MCDS). The predicted absolute yields (Gbp(-1) Gy(-1)) and RBE values for single-strand break (SSB) and double-strand break (DSB) induction by 220 kVp x-rays are within 1% of the results from detailed track-structure simulations (Friedland et al 1999 Radiat. Environ. Biophys. 38 39). The measured RBE for DSB induction reported by Kühne et al (2005 Radiat. Res. 164 669) for gamma-rays from (60)Co and for 29 kVp x-rays with a 50 microm Rh (mammography) filter are in excellent agreement (1.15 versus 1.16). DSB yields predicted by the MCDS also agree to within 7% with the absolute DSB yields reported by de Lara et al (2001 Radiat. Res. 155 440) and Botchway et al (1997 Radiat. Res. 148 317) for the irradiation of V79 cells by low energy (<2 keV) characteristic x-rays. The predicted RBE for DSB induction by gamma-rays from bare (169)Yb and (131)Cs to (60)Co are 1.06 and 1.14, respectively. Tabulated RBE values for the single-cell and monolayer cell culture geometries differ by at most 15%. The proposed methodology is computationally efficient and may also be useful for the prediction of damage yields for mixtures of other types of charged particles, such as those found in proton therapy, space applications or internal dosimetry.

The aim of this study was to investigate the effect of static magnetic field (SMF) exposure in antioxidant enzyme activity, the labile zinc fraction and DNA damage in THP1 cells (monocyte line). Cell culture flasks were exposed to SMF (250 mT) during 1 h (group 1), 2 h (group 2) and 3 h (group 3). Our results showed that cell viability was slightly lower in SMF-exposed groups compared to a sham exposed group. However, SMF exposure failed to alter malondialdehyde (MDA) concentration (+6%, p>0.05) and glutathione peroxidase (GPx) (-5%, p>0.05), catalase (CAT) (-6%, p>0.05) and superoxide dismutase (SOD) activities (+38%, p>0.05) in group 3 compared to the sham exposed group. DNA analysis by single cell gel electrophoresis (comet assay) revealed that SMF exposure did not exert any DNA damage in groups 1 and 2. However, it induced a low level of DNA single strand breaks in cells of group 3. To further explore the oxidative DNA damage, cellular DNA for group 3 was isolated, hydrolyzed and analysed by HPLC-EC. The level of 8-oxodGuo in this group remained unchanged compared to the sham exposed group (+6.5%, p>0.05). Cells stained with zinc-specific fluorescent probes zinpyr-1 showed a decrease of labile zinc fraction in all groups exposed to SMF. Our data showed that SMF exposure (250 mT, during 3 h) did not cause oxidative stress and DNA damage in THP1 cells. However, SMF could alter the intracellular labile zinc fraction.