AUTHOR=Adrian Gabriel , Konradsson Elise , Beyer Sarah , Wittrup Anders , Butterworth Karl T. , McMahon Stephen J. , Ghita Mihaela , Petersson Kristoffer , Ceberg Crister 

TITLE=Cancer Cells Can Exhibit a Sparing FLASH Effect at Low Doses Under Normoxic In Vitro-Conditions

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.686142

DOI=10.3389/fonc.2021.686142

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Irradiation with ultra-high dose rate (FLASH) has been shown to spare normal tissue without hampering tumor control in several <italic>in vivo</italic> studies. Few cell lines have been investigated <italic>in vitro</italic>, and previous results are inconsistent. Assuming that oxygen depletion accounts for the FLASH sparing effect, no sparing should appear for cells irradiated with low doses in normoxia.</p></sec><sec><title>Methods</title><p>Seven cancer cell lines (MDA-MB-231, MCF7, WiDr, LU-HNSCC4, HeLa [early passage and subclone]) and normal lung fibroblasts (MRC-5) were irradiated with doses ranging from 0 to 12 Gy using FLASH (≥800 Gy/s) or conventional dose rates (CONV, 14 Gy/min), with a 10 MeV electron beam from a clinical linear accelerator. Surviving fraction (SF) was determined with clonogenic assays. Three cell lines were further studied for radiation-induced DNA-damage foci using a 53BP1-marker and for cell cycle synchronization after irradiation.</p></sec><sec><title>Results</title><p>A tendency of increased survival following FLASH compared with CONV was suggested for all cell lines, with significant differences for 4/7 cell lines. The magnitude of the FLASH-sparing expressed as a dose-modifying factor at SF=0.1 was around 1.1 for 6/7 cell lines and around 1.3 for the HeLa<sub>subclone</sub>. Similar cell cycle distributions and 53BP1-foci numbers were found comparing FLASH to CONV.</p></sec><sec><title>Conclusion</title><p>We have found a FLASH effect appearing at low doses under normoxic conditions for several cell lines <italic>in vitro</italic>. The magnitude of the FLASH effect differed between the cell lines, suggesting inherited biological susceptibilities for FLASH irradiation.</p></sec>