Low-Dose Hypersensitivity and Bystander Effect are Not Mutually Exclusive in A549 Lung Carcinoma Cells after Irradiation with Charged Particles.

The purpose of this study was to measure survival fraction of A549 lung carcinoma cells irradiated with charged particles of various LET and to determine mechanisms responsible for enhanced cell killing in the low-dose region. A549 cells were irradiated with a broadbeam of either 10 and 25 keV/μm protons or 100 keV/μm alpha particles and then processed for clonogenic assays and phospho-histone H3 staining. The survival fraction of unirradiated A549 cells co-cultured with irradiated cells was also evaluated. A549 cells were shown to exhibit low-dose hypersensitivity (HRS) for both protons and alpha particles. The dose threshold at which HRS occurs decreased with increasing linear energy transfer (LET), whereas αs, the initial survival curve slope, increased with increasing LET. In addition, the enhanced cell killing observed after irradiation with alpha particles was partly attributed to the bystander effect, due to the low proportion of hit cells at very low doses. Co-culture experiments suggest a gap junction-mediated bystander signal. Our results indicate that HRS is likely to be dependent on LET, and that a bystander effect and low-dose hypersensitivity may co-exist within a given cell line

Low-LET Proton Irradiation of A549 Non-small Cell Lung Adenocarcinoma Cells: Dose Response and RBE Determination.

Since 1957, broad proton beam radiotherapy with a spread out Bragg peak has been used for cancer treatment. More recently, studies on the use of proton therapy in the treatment of non-small cell lung cancer (NSCLC) were performed and although the benefit of using protons for the treatment of NSCLC is recognized, more work is needed to gather additional data for the understanding of cell response. Human A549 cell survival was evaluated by colony forming assay 11 days after 10 keV/μm proton beam irradiation at 0.1 and 1 Gy/min. The residual energy of the proton beam at the location of the irradiated cells was 3.9 MeV. In parallel, early effects on the cell viability and DNA damage were assessed and DNA synthesis was measured. The survival curve obtained was fitted with both the linear and the induced-repair models, as a hyper-radiosensitivity was evidenced at very low doses. Above 0.5 Gy, a linear shape was observed with the α parameter equal to 0.824 ± 0.029 Gy(-1). In addition, early cell death and cell proliferation arrest were enhanced. Moreover, a clear correlation between DNA damage and surviving fraction was observed. Finally, comparisons with X and γ ray results indicate that proton irradiation at 10 keV/μm enhanced the tumor radiosensitivity with a significant dose-dependent decrease in the survival fraction. The RBE value of 1.9 ± 0.4 obtained for a 10% survival support this observation

Comparison of X-ray and alpha particle effects on a human cancer and endothelial cells: Survival curves and gene expression profiles.

Tumours are now considered as complex tissues including endothelial cells of the tumour vasculature, which can decrease radiotherapy efficacy. It is thus important to better characterise the response of both types of cells to irradiation. This study investigated the effects of X-ray and alpha particle irradiation on cancer and endothelial cells

Effects of Alpha Particle and Proton Beam Irradiation as Putative Cross-Talk between A549 Cancer Cells and the Endothelial Cells in a Co-Culture System.

High-LET ion irradiation is being more and more often used to control tumors in patients. Given that tumors are now considered as complex organs composed of multiple cell types that can influence radiosensitivity, we investigated the effects of proton and alpha particle irradiation on the possible radioprotective cross-talk between cancer and endothelial cells

On the comparison of three methods of assessing beam quality for broad beam in vitro cell irradiation

The interaction of charged particles with living matter has recently attracted increasing interest in the field of biomedical applications such as hadron therapy, radioprotection and space radiation biology. Particle accelerators are particularly useful in this area. In vitro radiobiological studies with a broad beam configuration require beam homogeneity. The goal is to produce a dose distribution given to a cell population that is as close to uniform as possible. In this paper, we compare the results of three devices used to assess the beam quality for broad beam irradiation: a passivated implanted planar silicon (PIPS) particle detector, a position-sensitive solid state detector, which is camera-like, and a solid state nuclear track detector (CR39). The first device is a PIPS detector of 300 μm nominal depletion depth and an entrance window with a thickness of about 500 . It is collimated with a 0.5 mm aperture and mounted in air on an XY moving table as close as possible to the exit window of the beam line. The second device is a CMOS position-sensitive detector (technological process 0.6 μm AMS CUA), 112 × 112 pixels, with 153 × 153 μm2 pixel size. It allows the user to rapidly obtain dose uniformity over a surface of 1 × 1 cm2. During uniformity and dose rate assessment it is placed in air at the PIPS location. For both detectors, beam profile was obtained for various proton fluxes (from ∼5 × 104 to 106 particles cm-2 s -1). Preliminary tests were made with CR39 using 4 MeV He ++ ions. Results are analysed using Poisson distribution and cell hit probability. © 2011 Elsevier B.V. All rights reserved