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Irradiation at Ultra-High (FLASH) Dose Rates Reduces Acute Normal Tissue Toxicity in the Mouse Gastrointestinal System.

التفاصيل البيبلوغرافية
العنوان: Irradiation at Ultra-High (FLASH) Dose Rates Reduces Acute Normal Tissue Toxicity in the Mouse Gastrointestinal System.
المؤلفون: Ruan JL; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom., Lee C; Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, United Kingdom., Wouters S; Interdisciplinary Biosciences Group, Belgian Nuclear Research Center (SCK CEN), Mol, Belgium; Molecular Pathology Group, Cell Biology and Histology and Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Campus Drie Eiken, University of Antwerp, Antwerp, Belgium., Tullis IDC; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom., Verslegers M; Interdisciplinary Biosciences Group, Belgian Nuclear Research Center (SCK CEN), Mol, Belgium., Mysara M; Interdisciplinary Biosciences Group, Belgian Nuclear Research Center (SCK CEN), Mol, Belgium., Then CK; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom., Smart SC; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom., Hill MA; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom., Muschel RJ; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom., Giaccia AJ; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom., Vojnovic B; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom., Kiltie AE; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom., Petersson K; MRC Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom; Radiation Physics, Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden. Electronic address: kristoffer.petersson@oncology.ox.ac.uk.
المصدر: International journal of radiation oncology, biology, physics [Int J Radiat Oncol Biol Phys] 2021 Dec 01; Vol. 111 (5), pp. 1250-1261. Date of Electronic Publication: 2021 Aug 14.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier, Inc Country of Publication: United States NLM ID: 7603616 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-355X (Electronic) Linking ISSN: 03603016 NLM ISO Abbreviation: Int J Radiat Oncol Biol Phys Subsets: MEDLINE
أسماء مطبوعة: Publication: New York, NY : Elsevier, Inc
Original Publication: Elmsford, N. Y., Pergamon Press.
مواضيع طبية MeSH: Gastrointestinal Tract* , Particle Accelerators*, Animals ; Mice ; Mice, Inbred C3H ; RNA, Ribosomal, 16S ; Radiotherapy Dosage
مستخلص: Purpose: Preclinical studies using ultra-high dose rate (FLASH) irradiation have demonstrated reduced normal tissue toxicity compared with conventional dose rate (CONV) irradiation, although this finding is not universal. We investigated the effect of temporal pulse structure and average dose rate of FLASH compared with CONV irradiation on acute intestinal toxicity.
Materials and Methods: Whole abdomens of C3H mice were irradiated with a single fraction to various doses, using a 6 MeV electron linear accelerator with single pulse FLASH (dose rate = 2-6 × 10 6 Gy/s) or conventional (CONV; 0.25 Gy/s) irradiation. At 3.75 days postirradiation, fresh feces were collected for 16S rRNA sequencing to assess changes in the gut microbiota. A Swiss roll-based crypt assay was used to quantify acute damage to the intestinal crypts to determine how tissue toxicity was affected by the different temporal pulse structures of FLASH delivery.
Results: We found statistically significant improvements in crypt survival for mice irradiated with FLASH at doses between 7.5 and 12.5 Gy, with a dose modifying factor of 1.1 for FLASH (7.5 Gy, P < .01; 10 Gy, P < .05; 12.5 Gy, P < .01). This sparing effect was lost when the delivery time was increased, either by increasing the number of irradiation pulses or by prolonging the time between 2 successive pulses. Sparing was observed for average dose rates of ≥280 Gy/s. Fecal microbiome analysis showed that FLASH irradiation caused fewer changes to the microbiota than CONV irradiation.
Conclusions: This study demonstrates that FLASH irradiation can spare mouse small intestinal crypts and reduce changes in gut microbiome composition compared with CONV irradiation. The higher the average dose rate, the larger the FLASH effect, which is also influenced by temporal pulse structure of the delivery.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
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معلومات مُعتمدة: C6078/A28736 United Kingdom CRUK_ Cancer Research UK; MC_UU_00001/8 United Kingdom MRC_ Medical Research Council; MC_UU_00001/9 United Kingdom MRC_ Medical Research Council; 23279 United Kingdom CRUK_ Cancer Research UK; 28736 United Kingdom CRUK_ Cancer Research UK
المشرفين على المادة: 0 (RNA, Ribosomal, 16S)
تواريخ الأحداث: Date Created: 20210817 Date Completed: 20220225 Latest Revision: 20240403
رمز التحديث: 20240403
مُعرف محوري في PubMed: PMC7612009
DOI: 10.1016/j.ijrobp.2021.08.004
PMID: 34400268
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-355X
DOI:10.1016/j.ijrobp.2021.08.004