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Abstract Radiation delivery at ultrahigh dose rates (UHDRs) has potential for use as a new anticancer therapeutic strategy. The FLASH effect induced by UHDR irradiation has been shown to maintain antitumour efficacy with a reduction in normal tissue toxicity; however, the FLASH effect has been difficult to demonstrate in vitro. The objective to demonstrate the FLASH effect in vitro is challenging, aiming to reveal a differential response between cancer and normal cells to further identify cell molecular mechanisms. New high-intensity petawatt laser-driven accelerators can deliver very high-energy electrons (VHEEs) at dose rates as high as 1013 Gy/s in very short pulses (10–13 s). Here, we present the first in vitro experiments carried out on cancer cells and normal non-transformed cells concurrently exposed to laser-plasma accelerated (LPA) electrons. Specifically, melanoma cancer cells and normal melanocyte co-cultures grown on chamber slides were simultaneously irradiated with LPA electrons. A non-uniform dose distribution on the cell cultures was revealed by Gafchromic films placed behind the chamber slide supporting the cells. In parallel experiments, cell co-cultures were exposed to pulsed X-ray irradiation, which served as positive controls for radiation-induced nuclear DNA double-strand breaks. By measuring the impact on discrete areas of the cell monolayers, the greatest proportion of the damaged DNA-containing nuclei was attained by the LPA electrons at a cumulative dose one order of magnitude lower than the dose obtained by pulsed X-ray irradiation. Interestingly, in certain discrete areas, we observed that LPA electron exposure had a different effect on the DNA damage in healthy normal human epidermal melanocyte (NHEM) cells than in A375 melanoma cells; here, the normal cells were less affected by the LPA exposure than cancer cells. This result is the first in vitro demonstration of a differential response of tumour and normal cells exposed to FLASH irradiation and may contribute to the development of new cell culture strategies to explore fundamental understanding of FLASH-induced cell effect.

High-power pulsed lasers are used more and more as tools for particle acceleration. Characterization of the accelerated particles in real-time and monitoring of the electromagnetic pulses (EMPs) during particle acceleration are critical challenges in laser acceleration experiments. Here, we used the CETAL-PW laser facility at NILPRP for particle acceleration from different thin metallic targets, at laser intensities of the order of 3×1021 W/cm2. We investigated the dependence of EMP amplitude (EMPA) and the accelerated electrons’ maximal energy (AEME), on thickness, resistivity, and atomic number of the target. We have found a quasi-linear dependence between EMPA and AEME and propose an analytical model for the GHz EMP emission. The model considers the neutralization current flowing through the target stalk as the main source of the EMP in the GHz domain, the current being produced by the positive charge accumulated on the target after the electron’s acceleration from the rear side of a metallic target. The data presented here support the possibility of using EMP signals to characterize the laser-accelerated particles in a real-time non-invasive way.

An adequate simulation model has been used for the calculation of angular and energy distributions of electrons, protons, and photons emitted during a high-power laser, 5-µm thick Ag target interaction. Their energy spectra and fluencies have been calculated between 0 and 360 degrees around the interaction point with a step angle of five degrees. Thus, the contribution of each ionizing species to the total fluency value has been established. Considering the geometry of the experimental set-up, a map of the radiation dose inside the target vacuum chamber has been simulated, using the Geant4 General Particle Source code, and further compared with the experimental one. Maximum values of the measured dose of the order of tens of mGy per laser shot have been obtained in the direction normal to the target at about 30 cm from the interaction point.

We show that a spectral distribution of laser-accelerated protons can be extracted by analyzing the proton track diameters observed on the front side of a second CR-39 detector arranged in a stack. The correspondence between the proton track diameter and the incident energy on the second detector is established by knowing that protons with energies only higher than 10.5 MeV can fully deposit their energy in the second CR-39 detector. The correlation between the laser-accelerated proton track diameters observed on the front side of the second CR-39 detector and the proton incident energy on the detector stack is also presented. By calculating the proton number stopped in the CR-39 stack, we find out that its dependence on the proton energy in the 1−15 MeV range presents some discontinuities at energies higher than 9 MeV. Thus, we build a calibration curve of the track diameter as a function of the proton incident energy within the 1−9 MeV range, and we infer the associated analytical function as the calculations performed indicate best results for proton spectra within the 1−9 MeV range. The calibration curve is used as a tool to ascertain the pits identified on the surfaces of both CR-39 detectors to proton tracks. The proton tracks spatial distribution analyzed by optical and atomic force microscopy is correlated with the peculiarity of the used targets.

Abstract Intense electromagnetic fields (EMFs) induce DNA double stranded breaks (DSBs) in exposed lymphocytes.We study developing pre-B lymphocytes following V(D)J recombination at their Immunoglobulin light chain loci (IgL). Recombination physiologically induces DNA DSBs, and we tested if low doses of EMF irradiation affect this developmental stage. Recombining pre-B cells, were exposed for 48 h to low intensity EMFs (maximal radiative power density flux S of 9.5 µW/cm2 and electric field intensity 3 V/m) from waves of frequencies ranging from 720 to 1224 MHz. Irradiated pre-B cells show decreased levels of recombination, reduction which is dependent upon the power dose and most remarkably upon the frequency of the applied EMF. Although 50% recombination reduction cannot be obtained even for an S of 9.5 µW/cm2 in cells irradiated at 720 MHz, such an effect is reached in cells exposed to only 0.45 µW/cm2 power with 950 and 1000 MHz waves. A maximal four-fold recombination reduction was measured in cells exposed to 1000 MHz waves with S from 0.2 to 4.5 µW/cm2 displaying normal levels of γH2AX phosphorylated histone. Our findings show that developing B cells exposure to low intensity EMFs can affect the levels of production and diversity of their antibodies repertoire.