Titre

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice.

Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Favaudon, V.
Auteure/Auteur
Caplier, L.
Auteure/Auteur
Monceau, V.
Auteure/Auteur
Pouzoulet, F.
Auteure/Auteur
Sayarath, M.
Auteure/Auteur
Fouillade, C.
Auteure/Auteur
Poupon, M.F.
Auteure/Auteur
Brito, I.
Auteure/Auteur
Hupé, P.
Auteure/Auteur
Bourhis, J.
Auteure/Auteur
Hall, J.
Auteure/Auteur
Fontaine, J.J.
Auteure/Auteur
Vozenin, M.C.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1946-6242
Statut éditorial
Publié
Date de publication
2014
Volume
6
Numéro
245
Première page
245ra93
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish, pdf : Research Article
Résumé
In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.
PID Serval
serval:BIB_6BEAFB335D2A
DOI
PMID
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Date de création
2014-12-01T15:37:47.737Z
Date de création dans IRIS
2025-05-21T03:34:08Z