First in vitro cell co-culture experiments using laser-induced high-energy electron FLASH irradiation for the development of anti-cancer therapeutic strategies.

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.

The Effects of Electron Beam Irradiation on the Morphological and Physicochemical Properties of Magnesium-Doped Hydroxyapatite/Chitosan Composite Coatings.

This work reports on the influence of 5 MeV electron beam radiations on the morphological features and chemical structure of magnesium-doped hydroxyapatite/chitosan composite coatings generated by the magnetron sputtering technique. The exposure to ionizing radiation in a linear electron accelerator dedicated to medical use has been performed in a controllable manner by delivering up to 50 Gy radiation dose in fractions of 2 Gy radiation dose per 40 s. After the irradiation with electron beams, the surface of layers became nano-size structured. The partial detachment of irradiated layers from the substrates has been revealed only after visualizing their cross sections by scanning electron microscopy. The energy dispersive X-ray spectral analysis of layer cross-sections indicated that the distribution of chemical elements in the samples depends on the radiation dose. The X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and X-ray diffraction analysis have shown that the physicochemical processes induced by the ionizing radiation in the magnesium doped hydroxyapatite/chitosan composite coatings do not alter the apatite structure, and Mg remains bonded with the phosphate groups.

Y2O3 Nanoparticles and X-ray Radiation-Induced Effects in Melanoma Cells.

The innovative strategy of using nanoparticles in radiotherapy has become an exciting topic due to the possibility of simultaneously improving local efficiency of radiation in tumors and real-time monitoring of the delivered doses. Yttrium oxide (Y2O3) nanoparticles (NPs) are used in material science to prepare phosphors for various applications including X-ray induced photodynamic therapy and in situ nano-dosimetry, but few available reports only addressed the effect induced in cells by combined exposure to different doses of superficial X-ray radiation and nanoparticles. Herein, we analyzed changes induced in melanoma cells by exposure to different doses of X-ray radiation and various concentrations of Y2O3 NPs. By evaluation of cell mitochondrial activity and production of intracellular reactive oxygen species (ROS), we estimated that 2, 4, and 6 Gy X-ray radiation doses are visibly altering the cells by inducing ROS production with increasing the dose while at 6 Gy the mitochondrial activity is also affected. Separately, high-concentrated solutions of 25, 50, and 100 µg/mL Y2O3 NPs were also found to affect the cells by inducing ROS production with the increase of concentration. Additionally, the colony-forming units assay evidenced a rather synergic effect of NPs and radiation. By adding the NPs to cells before irradiation, a decrease of the number of proliferating cell colonies was observed with increase of X-ray dose. DNA damage was evidenced by quantifying the γ-H2AX foci for cells treated with Y2O3 NPs and exposed to superficial X-ray radiation. Proteomic profile confirmed that a combined effect of 50 µg/mL Y2O3 NPs and 6 Gy X-ray dose induced mitochondria alterations and DNA changes in melanoma cells.

On within sample homogeneity testing using gamma-ray spectrometry.

Several problems concerning (133)Ba activity distribution in a cylindrical source were addressed by measurements with a 47% n-type HPGe detector and by simulation. Within-sample homogeneity was tested using the count rates from normal and from pure sum peaks. The sensitivity of front versus back source measurements to deviations from uniform distribution was studied. In the case of distributions symmetric with respect to the median plane of the source quantities that can provide information on the distribution of the activity were proposed.