Abstract
Laser-driven accelerators allow to generate ultrashort (from femto- to picoseconds) high peak dose-rate (up to tens of GGy/s) accelerated particle beams. However, the radiobiological effects of ultrashort pulsed irradiation are still poorly studied. The aim of this work was to compare the formation and elimination of γH2AX and 53BP1 foci (well known markers for DNA double-strand breaks (DSBs)) in Hela cells exposed to ultrashort pulsed electron beams generated by Advanced Research Electron Accelerator Laboratory (AREAL) accelerator (electron energy 3.6 MeV, pulse duration 450 fs, pulse repetition rates 2 or 20 Hz) and quasi-continuous radiation generated by Varian accelerator (electron energy 4 MeV) at doses of 250–1000 mGy. Additionally, a study on the dose–response relationships of changes in the number of residual γH2AX foci in HeLa and A549 cells 24 h after irradiation at doses of 500–10,000 mGy were performed. We found no statistically significant differences in γH2AX and 53BP1 foci yields at 1 h after exposure to 2 Hz ultrashort pulse vs. quasi-continuous radiations. In contrast, 20 Hz ultrashort pulse irradiation resulted in 1.27-fold higher foci yields as compared to the quasi-continuous one. After 24 h of pulse irradiation at doses of 500–10,000 mGy the number of residual γH2AX foci in Hela and A549 cells was 1.7–2.9 times higher compared to that of quasi-continuous irradiation. Overall, the obtained results suggest the slower repair rate for DSBs induced by ultrashort pulse irradiation in comparison to DSBs induced by quasi-continuous irradiation.
Highlights
In recent years, laser-generated particles’ acceleration technologies have been actively developed
Comparative analysis of γH2AX and 53BP1 foci yields was performed at 1 h post-irradiation and 0.25–1.0 Gy doses, following cells the irradiation on Advanced Research Electron Accelerator Laboratory (AREAL) and Varian accelerators
It has been shown that following irradiation using the AREAL accelerator at a 20 Hz repetition rate, a dose-dependent increase in foci numbers was described with a high fit (R2 = 0.99, p < 0.001) by y = 3.57 + 22.29 × x linear equation, where y is an average of foci numbers in a cell nucleus and x is an irradiation dose (Gy)
Summary
Laser-generated particles’ acceleration technologies have been actively developed. The duration of irradiation by single ultrashort pulse is far lower than the half-life (t1/2) of free radicals (e.g., hydroxyl radicals t1/2 is ~1 ns [7]), suggesting the appearance of previously unexplored physicochemical processes, which, in turn, can affect the radiobiological effectiveness of pulsed irradiation. From this perspective, the impact of ultrashort pulsed irradiation on DNA and on one of the most deleterious lesions, namely double strand breaks (DSBs) formation on both qualitative and quantitative levels is of high interest. Inability to repair of DSBs leads to cells death [12,13]
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