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

Adrian, Gabriel (författare)
Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
Konradsson, Elise (författare)
Lund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Radiotherapy Physics,Forskargrupper vid Lunds universitet,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
Beyer, Sarah (författare)
Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumörmikromiljön,Forskargrupper vid Lunds universitet,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Skåne University Hospital
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Wittrup, Anders (författare)
Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,WCMM- Wallenberg center för molekylär medicinsk forskning,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,WCMM-Wallenberg Centre for Molecular Medicine,Skåne University Hospital
Butterworth, Karl T. (författare)
Queen's University Belfast
McMahon, Stephen J. (författare)
Queen's University Belfast
Ghita, Mihaela (författare)
Queen's University Belfast
Petersson, Kristoffer (författare)
Skåne University Hospital,University of Oxford
Ceberg, Crister (författare)
Lund University,Lunds universitet,Medicinsk strålningsfysik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Radiotherapy Physics,Forskargrupper vid Lunds universitet,Rausinglaboratoriet i Lund - Tumörsektionen,Medical Radiation Physics, Lund,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,Rausing laboratory of Lund - Tumor section
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 (creator_code:org_t)
2021-07-29
2021
Engelska.
Ingår i: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 11
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • Background: Irradiation with ultra-high dose rate (FLASH) has been shown to spare normal tissue without hampering tumor control in several in vivo studies. Few cell lines have been investigated in vitro, 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. Methods: 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. Results: 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 HeLasubclone. Similar cell cycle distributions and 53BP1-foci numbers were found comparing FLASH to CONV. Conclusion: We have found a FLASH effect appearing at low doses under normoxic conditions for several cell lines in vitro. The magnitude of the FLASH effect differed between the cell lines, suggesting inherited biological susceptibilities for FLASH irradiation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
NATURVETENSKAP  -- Fysik -- Annan fysik (hsv//swe)
NATURAL SCIENCES  -- Physical Sciences -- Other Physics Topics (hsv//eng)

Nyckelord

cancer cell lines
clonogenic assay
FLASH
normoxia
radiobiology
radioresistance
radiotherapy
ultra-high dose rate irradiation

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