Pavel N Lobachevsky1, Jessica Ventura2, Lina Giannakandropoulou3, Helen Forrester4, Jason S Palazzolo5, Nicole M Haynes6, Andrew W Stevenson7, Christopher J Hall8, Joel Mason5, Gerasimos Pollakis3, Ioannis S Pateras9, Vassilis Gorgoulis10, Georgia I Terzoudi11, John A Hamilton12, Carl N Sprung4, Alexandros G Georgakilas3, Olga A Martin13. 1. Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia. 2. University of Melbourne Department of Obstetrics & Gynaecology and Royal Women's Hospital. 3. School of Applied Mathematical & Physical Sciences, National Technical University of Athens, Athens, Greece. 4. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research and Monash University, Clayton, Victoria, Australia. 5. Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 6. Cancer Therapeutics Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 7. Commonwealth Scientific and Industrial Research Organisation, Clayton, Victoria, Australia; Australian Synchrotron, Clayton, Victoria, Australia. 8. Australian Synchrotron, Clayton, Victoria, Australia. 9. Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece. 10. Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Athens, Greece; Biomedical Research Foundation, Academy of Athens, Athens, Greece; Institute for Cancer Sciences and Manchester Centre for Cellular Metabolism, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom. 11. Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research 'Demokritos', Athens, Greece. 12. Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia; Australian Institute for Musculoskeletal Science (AIMSS), University of Melbourne and Western Health, St. Albans, Victoria, Australia. 13. Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Electronic address: olga.martin@petermac.org.
Abstract
PURPOSE: Nontargeted effects of ionizing radiation, by which unirradiated cells and tissues are also damaged, are a relatively new paradigm in radiobiology. We recently reported radiation-induced abscopal effects (RIAEs) in normal tissues; namely, DNA damage, apoptosis, and activation of the local and systemic immune responses in C57BL6/J mice after irradiation of a small region of the body. High-dose-rate, synchrotron-generated broad beam or multiplanar x-ray microbeam radiation therapy was used with various field sizes and doses. This study explores components of the immune system involved in the generation of these abscopal effects. METHODS AND MATERIALS: The following mice with various immune deficiencies were irradiated with the microbeam radiation therapy beam: (1) SCID/IL2γR-/- (NOD SCID gamma, NSG) mice, (2) wild-type C57BL6/J mice treated with an antibody-blocking macrophage colony-stimulating factor 1 receptor, which depletes and alters the function of macrophages, and (3) chemokine ligand 2/monocyte chemotactic protein 1 null mice. Complex DNA damage (ie, DNA double-strand breaks), oxidatively induced clustered DNA lesions, and apoptotic cells in tissues distant from the irradiation site were measured as RIAE endpoints and compared with those in wild-type C57BL6/J mice. RESULTS: Wild-type mice accumulated double-strand breaks, oxidatively induced clustered DNA lesions, and apoptosis, enforcing our RIAE model. However, these effects were completely or partially abrogated in mice with immune disruption, highlighting the pivotal role of the immune system in propagation of systemic genotoxic effects after localized irradiation. CONCLUSIONS: These results underline the importance of not only delineating the best strategies for tumor control but also mitigating systemic radiation toxicity.
PURPOSE: Nontargeted effects of ionizing radiation, by which unirradiated cells and tissues are also damaged, are a relatively new paradigm in radiobiology. We recently reported radiation-induced abscopal effects (RIAEs) in normal tissues; namely, DNA damage, apoptosis, and activation of the local and systemic immune responses in C57BL6/J mice after irradiation of a small region of the body. High-dose-rate, synchrotron-generated broad beam or multiplanar x-ray microbeam radiation therapy was used with various field sizes and doses. This study explores components of the immune system involved in the generation of these abscopal effects. METHODS AND MATERIALS: The following mice with various immune deficiencies were irradiated with the microbeam radiation therapy beam: (1) SCID/IL2γR-/- (NOD SCID gamma, NSG) mice, (2) wild-type C57BL6/J mice treated with an antibody-blocking macrophage colony-stimulating factor 1 receptor, which depletes and alters the function of macrophages, and (3) chemokine ligand 2/monocyte chemotactic protein 1 null mice. Complex DNA damage (ie, DNA double-strand breaks), oxidatively induced clustered DNA lesions, and apoptotic cells in tissues distant from the irradiation site were measured as RIAE endpoints and compared with those in wild-type C57BL6/J mice. RESULTS: Wild-type mice accumulated double-strand breaks, oxidatively induced clustered DNA lesions, and apoptosis, enforcing our RIAE model. However, these effects were completely or partially abrogated in mice with immune disruption, highlighting the pivotal role of the immune system in propagation of systemic genotoxic effects after localized irradiation. CONCLUSIONS: These results underline the importance of not only delineating the best strategies for tumor control but also mitigating systemic radiation toxicity.
Authors: B Frey; J Mika; K Jelonek; L Cruz-Garcia; C Roelants; I Testard; N Cherradi; K Lumniczky; S Polozov; A Napieralska; P Widlak; U S Gaipl; C Badie; J Polanska; S M Candéias Journal: Strahlenther Onkol Date: 2020-06-09 Impact factor: 3.621
Authors: Pavel Lobachevsky; Helen B Forrester; Alesia Ivashkevich; Joel Mason; Andrew W Stevenson; Chris J Hall; Carl N Sprung; Valentin G Djonov; Olga A Martin Journal: Front Oncol Date: 2021-05-21 Impact factor: 6.244