Sparing Effect on Cell Survival Under Normoxia Using Ultra-high Dose Rate Proton Beams from a Compact Superconducting AVF Cyclotron

Abstract

Background/Aim: The purpose of this study was to evaluate whether the sparing effect on cell survival is observed under normoxia. Materials and Methods: A superconducting spiral sector-type azimuthally varying field (AVF) cyclotron produced 230 MeV proton beams at 250 Gy/s as ultra-high dose rate (uHDR) and 1 Gy/s as normal dose rate (NDR) to irradiate tumor and normal cell lines (HSGc-c5 and HDF up to 24 Gy at the center of spread-out Bragg peak (SOBP). The Advanced Markus chamber and Gafchromic film were used to measure the examined absolute dose and field sizes. Colony formation assay and immunofluorescence staining were conducted to evaluate the sparing effect. Results: A homogeneous field was achieved at the center of the SOBP for both uHDR and NDR scanned proton beams, and dose reproducibility and linearity were adequate for experiments. There were significant differences in cell surviving fractions of HSGc-C5 and HDF cells irradiated at uHDRs compared to NDRs at 20 Gy and 24 Gy. Increasing γ-H2AX foci were observed for both cell lines at NDR. Conclusion: The sparing effect on cell survival was first observed under normoxic conditions for tumor and normal cells with doses exceeding 20 Gy, using proton irradiation at 250 Gy/s extracted from a superconducting AVF cyclotron. This study marks a significant milestone in advancing our understanding of the underlying mechanism behind the sparing effect.