Irradiation at Ultra-High (FLASH) Dose Rates Reduces Acute Normal Tissue Toxicity in the Mouse Gastrointestinal System.
Journal
International journal of radiation oncology, biology, physics
ISSN: 1879-355X
Titre abrégé: Int J Radiat Oncol Biol Phys
Pays: United States
ID NLM: 7603616
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
received:
09
04
2021
revised:
03
08
2021
accepted:
04
08
2021
pubmed:
18
8
2021
medline:
26
2
2022
entrez:
17
8
2021
Statut:
ppublish
Résumé
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. 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 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. 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.
Identifiants
pubmed: 34400268
pii: S0360-3016(21)02643-2
doi: 10.1016/j.ijrobp.2021.08.004
pmc: PMC7612009
mid: EMS138176
pii:
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1250-1261Subventions
Organisme : Cancer Research UK
ID : 28736
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00001/8
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00001/9
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C6078/A28736
Pays : United Kingdom
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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