Effect of dose rate on antitumor activity in hypoxic cells by using flattening filter free beams

Background: recently, the flaening filter free (fff) beams, which allow a doserate increase of up to four times compared to the normal dose rate, have beenincorporated into radiation therapy machines. the aim of this study is to evaluateantitumor activity in hypoxic cells irradiated with different dose rates using fffbeams and to identify the casual mechanism for cellular damage during irradiation.materials and methods: emt6 cells were treated with 95% n2 and 5% co2 tomaintain a hypoxic condition. three dose rates, namely, 6.27 gy/min, 12.00 gy/min, and 18.82 gy/min, were used to deliver the prescribed dose of 2 to 4 gy usingthe truebeam linear accelerator. the number of colonies was counted to evaluatethe cell surviving fraction. to investigate the mode of action, additional experimentsto detect reactive oxygen species (ros) by aminophenyl fluorescein (apf) assay,and dna double-strand breaks (dsbs) by γh2ax assay were performed. results:irradiation of hypoxic cells using fff beams increases antitumor activity as afunction of dose rate. the fluorescence of the apf assay was significantlyincreased when high dose rates were used. in addition, results from ourγh2ax assays show that the number of dna dsbs increased as a function ofdose rate, in hypoxic cells. conclusion: we demonstrate that there is a significantdose rate-dependent difference in antitumor activity in hypoxic cells, when fffbeams are used.