Abstract
BackgroundCellular responses to proton beam irradiation are not yet clearly understood, especially differences in the relative biological effectiveness (RBE) of high-energy proton beams depending on the position on the Spread-Out Bragg Peak (SOBP). Towards this end, we investigated the differences in the biological effect of a high-energy proton beam on the target cells placed at different positions on the SOBP, using two human esophageal cancer cell lines with differing radiosensitivities.MethodsTwo human esophageal cancer cell lines (OE21, KYSE450) with different radiosensitivities were irradiated with a 235-MeV proton beam at 4 different positions on the SOBP (position #1: At entry; position #2: At the proximal end of the SOBP; position #3: Center of the SOBP; position #4: At the distal end of the SOBP), and the cell survivals were assessed by the clonogenic assay. The RBE10 for each position of the target cell lines on the SOBP was determined based on the results of the cell survival assay conducted after photon beam irradiation. In addition, the number of DNA double-strand breaks was estimated by quantitating the number of phospho-histone H2AX (γH2AX) foci formed in the nuclei by immunofluorescence analysis.ResultsIn regard to differences in the RBE of a proton beam according to the position on the SOBP, the RBE value tended to increase as the position on the SOBP moved distally. Comparison of the residual number of γH2AX foci at the end 24 h after the irradiation revealed, for both cell lines, a higher number of foci in the cells irradiated at the distal end of the SOPB than in those irradiated at the proximal end or center of the SOBP.ConclusionsThe results of this study demonstrate that the RBE of a high-energy proton beam and the cellular responses, including the DNA damage repair processes, to high-energy proton beam irradiation, differ according to the position on the SOBP, irrespective of the radiosensitivity levels of the cell lines.
Highlights
Cellular responses to proton beam irradiation are not yet clearly understood, especially differences in the relative biological effectiveness (RBE) of high-energy proton beams depending on the position on the Spread-Out Bragg Peak (SOBP)
To evaluate the difference in the cellular responses to the proton beam irradiation according to the position on the SOBP, the cells were irradiated at 4 different positions on the SOBP, which was 8 cm in width At entry (49 mm); position # 2) Just proximal to the SOBP (107 mm); position #3) Center of the SOBP (135 mm); position #4) Distal end, at the fall-off, of the SOBP (163 mm), at the dose rate of 6 Gy/min
Our findings indicate that the RBE as well as the cellular responses, including Deoxyribonucleic acid (DNA) damage repair processes, in response to proton beam irradiation differed according to the position on the SOBP
Summary
Cellular responses to proton beam irradiation are not yet clearly understood, especially differences in the relative biological effectiveness (RBE) of high-energy proton beams depending on the position on the Spread-Out Bragg Peak (SOBP). PBT is expected to be associated with reduced treatment-related toxicities, because of the unique physical characteristic of the proton beam, wherein the peak energy, represented by the so-called Bragg peak, is delivered just before the particles come to rest, with the energy declining rapidly thereafter [2, 6]. This indicates that in PBT, a higher dose can be delivered to the tumor, while keeping the dose to the surrounding normal tissues within an acceptable level. Evaluation of the RBE using human malignant cell lines has been limited until now, and there are no reports yet of evaluation of the RBE using human cancer cell lines exhibiting different levels of radiosensitivity
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