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- Title
Absence of Tissue-Sparing Effects in Partial Proton FLASH Irradiation in Murine Intestine.
- Authors
Zhang, Qixian; Gerweck, Leo E.; Cascio, Ethan; Gu, Liqun; Yang, Qingyuan; Dong, Xinyue; Huang, Peigen; Bertolet, Alejandro; Nesteruk, Konrad Pawel; Sung, Wonmo; McNamara, Aimee L.; Schuemann, Jan
- Abstract
Simple Summary: The normal tissue-sparing effect of ultra-high dose rate irradiation (i.e., FLASH effect) has been widely reported. However, our data suggest that not all irradiations with a dose rate above 40 Gy/s can confer benefits. We found that partial abdominal FLASH proton irradiation neither improved survival nor preserved circulating lymphocytes. These findings highlight the necessity to understand the conditions that induce the FLASH effect, for successful clinical translation. Ultra-high dose rate irradiation has been reported to protect normal tissues more than conventional dose rate irradiation. This tissue sparing has been termed the FLASH effect. We investigated the FLASH effect of proton irradiation on the intestine as well as the hypothesis that lymphocyte depletion is a cause of the FLASH effect. A 16 × 12 mm2 elliptical field with a dose rate of ~120 Gy/s was provided by a 228 MeV proton pencil beam. Partial abdominal irradiation was delivered to C57BL/6j and immunodeficient Rag1−/−/C57 mice. Proliferating crypt cells were counted at 2 days post exposure, and the thickness of the muscularis externa was measured at 280 days following irradiation. FLASH irradiation did not reduce the morbidity or mortality of conventional irradiation in either strain of mice; in fact, a tendency for worse survival in FLASH-irradiated mice was observed. There were no significant differences in lymphocyte numbers between FLASH and conventional-dose-rate mice. A similar number of proliferating crypt cells and a similar thickness of the muscularis externa following FLASH and conventional dose rate irradiation were observed. Partial abdominal FLASH proton irradiation at 120 Gy/s did not spare normal intestinal tissue, and no difference in lymphocyte depletion was observed. This study suggests that the effect of FLASH irradiation may depend on multiple factors, and in some cases dose rates of over 100 Gy/s do not induce a FLASH effect and can even result in worse outcomes.
- Subjects
ANIMAL experimentation; RADIATION; IMMUNOSUPPRESSION; PROTONS; RADIATION doses; HYPOTHESIS; RESEARCH funding; INTESTINES; MICE
- Publication
Cancers, 2023, Vol 15, Issue 8, p2269
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers15082269