Jérémy Lavigne1, Alexandra Suissa2, Nicolas Verger2, Morgane Dos Santos3, Mohamedamine Benadjaoud4, Laurence Mille-Hamard5, Iman Momken5, Frédéric Soysouvanh1, Valérie Buard2, Olivier Guipaud2, Vincent Paget2, Georges Tarlet2, Fabien Milliat2, Agnès François6. 1. Institut de Radioprotection et de Sûreté Nucléaire, Service de Recherche en Radiobiologie et en Médecine régénérative, Laboratoire de Radiobiologie des expositions Médicales, Fontenay-aux-Roses, France; Sorbonne Université, Collège Doctoral, Paris, France. 2. Institut de Radioprotection et de Sûreté Nucléaire, Service de Recherche en Radiobiologie et en Médecine régénérative, Laboratoire de Radiobiologie des expositions Médicales, Fontenay-aux-Roses, France. 3. Institut de Radioprotection et de Sûreté Nucléaire, Service de Recherche en Radiobiologie et en Médecine régénérative, Laboratoire de Radiobiologie des expositions Accidentelles, Fontenay-aux-Roses, France. 4. Institut de Radioprotection et de Sûreté Nucléaire, Service de Recherche en Radiobiologie et en Médecine régénérative, Fontenay-aux-Roses, France. 5. Unité de Biologie Intégrative des Adaptations à l'Exercice, Université Évry-Val-d'Essonne, Université Paris-Saclay, Evry, France. 6. Institut de Radioprotection et de Sûreté Nucléaire, Service de Recherche en Radiobiologie et en Médecine régénérative, Laboratoire de Radiobiologie des expositions Médicales, Fontenay-aux-Roses, France. Electronic address: Agnes.francois@irsn.fr.
Abstract
PURPOSE: Stereotactic body radiation therapy offers good lung local tumor control by the administration of a high dose per fraction in small volumes. Stereotactic body radiation therapy preclinical modeling is now possible, and our aim was to develop a model of focal irradiation of the mouse lung and to investigate the impact of conditional hypoxia-inducible factor 1α (HIF-1α) deletion in the endothelium on radiation-induced tissue damage. METHODS AND MATERIALS: The Small Animal Radiation Research Platform was used to create a mouse model of focal irradiation of the lung using arc therapy. HIF-1α conditional deletion was obtained by crossing mice expressing Cre recombinase under the endothelial promoter VE-cadherin (VECad-Cre+/+ mice) with HIF-1α floxed mice. RESULTS: Lung stereotactic arc therapy allows thoracic wall sparing and long-term studies. However, isodose curves showed that neighboring organs received significant doses of radiation, as revealed by ipsilateral lung acute red hepatization and major gene expression level modifications. Conditional HIF-1α deletion reduced acute lung edema and tended to diminish neutrophil infiltrate, but it had no impact on long-term global tissue damage. CONCLUSIONS: Arc therapy for focal high-dose irradiation of mouse lung is an efficient model for long-term studies. However, irradiation may have a strong impact on the structure and function of neighboring organs, which must be considered. HIF-1α conditional deletion has no beneficial impact on lung damage in this irradiation schedule.
PURPOSE: Stereotactic body radiation therapy offers good lung local tumor control by the administration of a high dose per fraction in small volumes. Stereotactic body radiation therapy preclinical modeling is now possible, and our aim was to develop a model of focal irradiation of the mouse lung and to investigate the impact of conditional hypoxia-inducible factor 1α (HIF-1α) deletion in the endothelium on radiation-induced tissue damage. METHODS AND MATERIALS: The Small Animal Radiation Research Platform was used to create a mouse model of focal irradiation of the lung using arc therapy. HIF-1α conditional deletion was obtained by crossing mice expressing Cre recombinase under the endothelial promoter VE-cadherin (VECad-Cre+/+ mice) with HIF-1α floxed mice. RESULTS: Lung stereotactic arc therapy allows thoracic wall sparing and long-term studies. However, isodose curves showed that neighboring organs received significant doses of radiation, as revealed by ipsilateral lung acute red hepatization and major gene expression level modifications. Conditional HIF-1α deletion reduced acute lung edema and tended to diminish neutrophil infiltrate, but it had no impact on long-term global tissue damage. CONCLUSIONS: Arc therapy for focal high-dose irradiation of mouse lung is an efficient model for long-term studies. However, irradiation may have a strong impact on the structure and function of neighboring organs, which must be considered. HIF-1α conditional deletion has no beneficial impact on lung damage in this irradiation schedule.
Authors: M Protopapa; V Kouloulias; A Kougioumtzopoulou; Z Liakouli; C Papadimitriou; A Zygogianni Journal: Clin Transl Oncol Date: 2019-06-28 Impact factor: 3.405
Authors: Annaïg Bertho; Morgane Dos Santos; Sarah Braga-Cohen; Valérie Buard; Vincent Paget; Olivier Guipaud; Georges Tarlet; Fabien Milliat; Agnès François Journal: Front Med (Lausanne) Date: 2021-12-24