Response of Cancer Stem Cells and Human Skin Fibroblasts to Picosecond-Scale Electron Irradiation at 10 10 to 10 11 Gy/s

This study aimed to demonstrate for the first time the possibility of irradiating biological cells with gray (Gy)-scale doses delivered over single bursts of picosecond-scale electron beams, resulting in unprecedented dose rates of 10 to 10 Gy/s. Cancer stem cells and human skin fibroblasts were irradiated with MeV-scale electron beams from a laser-driven source. Doses up to 3 Gy per pulse with a high spatial uniformity (coefficient of variance, 3%-6%) and within a timescale range of 10 to 20 picoseconds were delivered. Doses were characterized during irradiation and were found to be in agreement with Monte Carlo simulations. Cell survival and DNA double-strand break repair dynamics were studied for both cell lines using clonogenic assay and 53BP1 foci formation. The results were compared with reference x-rays at a dose rate of 0.49 Gy/min. Results from clonogenic assays of both cell lines up to 3 Gy were well fitted by a linear quadratic model with α = (0.68 ± 0.08) Gy and β = (0.01 ± 0.01) Gy for human skin fibroblasts and α = (0.51 ± 0.14) Gy and β = (0.01 ± 0.01) Gy for cancer stem cells. Compared with irradiation at 0.49 Gy/min, our experimental results indicate no statistically significant difference in cell survival rate for doses up to 3 Gy despite a significant increase in the α parameter, which may reflect more complex damage. Foci measurements showed no significant difference between irradiation at 10 Gy/s and at 0.49 Gy/min. This study demonstrates the possibility of performing radiobiological studies with picosecond-scale laser-generated electron beams at ultrahigh dose rates of 10 to10 Gy/s. Preliminary results indicate, within statistical uncertainties, a significant increase of the α parameter, a possible indication of more complex damage induced by a higher density of ionizing tracks.