Quantification of Differential Response of Tumour and Normal Cells to Microbeam Radiation in the Absence of FLASH Effects
Open Access
- 29 June 2021
- Vol. 13 (13), 3238
- https://doi.org/10.3390/cancers13133238
Abstract
Microbeam radiotherapy (MRT) is a preclinical method of delivering spatially-fractionated radiotherapy aiming to improve the therapeutic window between normal tissue complication and tumour control. Previously, MRT was limited to ultra-high dose rate synchrotron facilities. The aim of this study was to investigate in vitro effects of MRT on tumour and normal cells at conventional dose rates produced by a bench-top X-ray source. Two normal and two tumour cell lines were exposed to homogeneous broad beam (BB) radiation, MRT, or were separately irradiated with peak or valley doses before being mixed. Clonogenic survival was assessed and compared to BB-estimated surviving fractions calculated by the linear-quadratic (LQ)-model. All cell lines showed similar BB sensitivity. BB LQ-model predictions exceeded the survival of cell lines following MRT or mixed beam irradiation. This effect was stronger in tumour compared to normal cell lines. Dose mixing experiments could reproduce MRT survival. We observed a differential response of tumour and normal cells to spatially fractionated irradiations in vitro, indicating increased tumour cell sensitivity. Importantly, this was observed at dose rates precluding the presence of FLASH effects. The LQ-model did not predict cell survival when the cell population received split irradiation doses, indicating that factors other than local dose influenced survival after irradiation.Funding Information
- Cancer Research UK (C33589/A1972, C57410/A21787, S1456)
This publication has 50 references indexed in Scilit:
- Response of the rat spinal cord to X-ray microbeamsRadiotherapy and Oncology, 2013
- Susceptibility to bystander DNA damage is influenced by replication and transcriptional activityNucleic Acids Research, 2012
- Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluationBMC Biology, 2012
- Detailed interrogation of trypanosome cell biology via differential organelle staining and automated image analysisBMC Biology, 2012
- Effects of pulsed, spatially fractionated, microscopic synchrotron X-ray beams on normal and tumoral brain tissueMutation research. Reviews in mutation research, 2010
- Radiation-induced bystander signalling in cancer therapyNature Reviews Cancer, 2009
- Predicting the clonogenic survival of A549 cells after modulated x-ray irradiation using the linear quadratic modelPhysics in Medicine & Biology, 2008
- Irradiation of intracerebral 9L gliosarcoma by a single array of microplanar x-ray beams from a synchrotron: balance between curing and sparingPhysics in Medicine & Biology, 2008
- The third dimension bridges the gap between cell culture and live tissueNature Reviews Molecular Cell Biology, 2007
- The linear-quadratic formula and progress in fractionated radiotherapyThe British Journal of Radiology, 1989