Abstract
The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in order to assess the yields of early DNA damage, in particular of double-strand breaks (DSBs). The simulation of these irradiations was set in order to understand the differences in the obtained experimental results. Hence, simulated results in terms of microdosimetric spectra and early DSB induction were analyzed and compared to the experimental data. Human umbilical vein endothelial cells (HUVECs) were irradiated with 40, 220 kVp, and 4 MV X-rays. The Geant4 Monte Carlo simulation toolkit and its extension Geant4-DNA were used for the simulations. Microdosimetric calculations aiming to determine possible differences in the variability of the energy absorbed by the irradiated cell population for those photon spectra were performed on 10,000 endothelial cell nuclei representing a cell monolayer. Nanodosimetric simulations were also carried out using a computation chain that allowed the simulation of physical, physico-chemical, and chemical stages on a single realistic endothelial cell nucleus model including both heterochromatin and euchromatin. DNA damage was scored in terms of yields of prompt DSBs per Gray (Gy) and per giga (109) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (γ-H2AX) foci per cell. The calculated microdosimetric spread in the irradiated cell population was similar when comparing between 40 and 220 kVp X-rays and higher when comparing with 4 MV X-rays. Simulated yields of induced DSB/Gy/Gbp were found to be equivalent to those for 40 and 220 kVp but larger than those for 4 MV, resulting in a relative biological effectiveness (RBE) of 1.3. Additionally, DSB complexity was similar between the considered photon spectra. Simulated results were in good agreement with experimental data obtained by IRSN (Institut de radioprotection et de sûreté nucléaire) radiobiologists. Despite differences in photon energy, few differences were observed when comparing between 40 and 220 kVp X-rays in microdosimetric and nanodosimetric calculations. Nevertheless, variations were observed when comparing between 40/220 kVp and 4 MV X-rays. Thanks to the simulation results, these variations were able to be explained by the differences in the production of secondary electrons with energies below 10 keV.
Highlights
For the evaluation of DNA damage induced by photon irradiation, most radiobiological experiments rely on the mean absorbed dose [1]
It could be assumed that these variations could lead to differences in terms of energy depositions because this could give rise to different secondary electron spectra
The photon spectra are different, but we can observe that the distributions of secondary electrons resulting from both 40 and 220 kVp X-rays are quite similar, as well as their mean energies (9.8 and 18.4 keV, respectively), if we account for the fact that the acceleration potential increases almost six times
Summary
For the evaluation of DNA damage induced by photon irradiation, most radiobiological experiments rely on the mean absorbed dose [1]. Very low energy X-rays may lead to higher risk estimates at low doses for many biological endpoints such as double-strand breaks (DSBs), chromosome aberrations, micronucleus formation, and cell survival [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22] This could be explained by the fact that energy depositions vary between these different photon energies since the type of interaction (photoelectric effect, Compton effect, or pair production), which causes the energy deposition depends on the photon energy [23]. The stochastic nature of the radiation–tissue interaction leads to differences in terms of energy received by each cell nucleus in a cell population [1], which can be analyzed through microdosimetry
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