A functional immune system is required for the systemic genotoxic effects of localized irradiation

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dc.contributor.authorLobachevsky, PNen_AU
dc.contributor.authorVentura, Jen_AU
dc.contributor.authorGiannakandropoulou, Len_AU
dc.contributor.authorForrester, HBen_AU
dc.contributor.authorPalazzolo, JSen_AU
dc.contributor.authorHaynes, NMen_AU
dc.contributor.authorStevenson, AWen_AU
dc.contributor.authorHall, CJen_AU
dc.contributor.authorMason, Jen_AU
dc.contributor.authorPollakis, Gen_AU
dc.contributor.authorPateras, ISen_AU
dc.contributor.authorGorgoulis, Ven_AU
dc.contributor.authorTerzoudi, GIen_AU
dc.contributor.authorHamilton, JAen_AU
dc.contributor.authorSprung, CNen_AU
dc.contributor.authorGeorgakilas, AGen_AU
dc.contributor.authorMartin, OAen_AU
dc.date.accessioned2025-02-28T02:24:06Zen_AU
dc.date.available2025-02-28T02:24:06Zen_AU
dc.date.issued2019-04-01en_AU
dc.date.statistics2025-02-19en_AU
dc.description.abstractPurpose: 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. © 2018 Elsevier Incen_AU
dc.description.sponsorshipH.F. and C.N.S. were supported by the 2010 round of the priority-driven Collaborative Cancer Research Scheme (grant #1002743), by the Australian Government Department of Health and Ageing, with the assistance of Cancer Australia, and by the Victorian Government's Operational Infrastructure Support Program. A.W.S. and C.J.H. were supported by the Australian Synchrotron. J.V. was supported by the Felix Meyer Scholarship in Obstetrics and Gynecology, University of Melbourne. V.G. and I.S.P. received financial support by SARG-NKUA grants #70/3/12128 and 70/3/8916. A.G.G., L.G., and G.P. acknowledge the support by DAAD grant #57339330.en_AU
dc.format.mediumPrint-Electronicen_AU
dc.identifier.citationLobachevsky, P. N., Ventura, J., Giannakandropoulou, L., Forrester, H., Palazzolo, J. S., Haynes, N. M., Stevenson, A. W., Hall, C. J., Mason, J., Pollakis, G., Pateras, I. S., Gorgoulis, V., Terzoudi, G. I., Hamilton, J. A., Sprung, C. N., Georgakilas, A. G., & Martin, O. A. (2019). A functional immune system is required for the systemic genotoxic effects of localized irradiation. International Journal of Radiation Oncology*Biology*Physics, 103(5), 1184-1193. doi:10.1016/j.ijrobp.2018.11.066en_AU
dc.identifier.issn0360-3016en_AU
dc.identifier.issn1879-355Xen_AU
dc.identifier.issue5en_AU
dc.identifier.journaltitleInternational Journal of Radiation Oncology*Biology*Physicsen_AU
dc.identifier.pagination1184-1193en_AU
dc.identifier.urihttps://doi.org/10.1016/j.ijrobp.2018.11.066en_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/16009en_AU
dc.identifier.volume103en_AU
dc.languageEnglishen_AU
dc.language.isoenen_AU
dc.publisherElsevieren_AU
dc.subjectImmune Serumsen_AU
dc.subjectIrradiationen_AU
dc.subjectToxicityen_AU
dc.subjectDNA damagesen_AU
dc.subjectDose ratesen_AU
dc.subjectSynchrotronsen_AU
dc.subjectIonizing radiationsen_AU
dc.subjectImmune system diseasesen_AU
dc.subjectMiceen_AU
dc.subjectDNAen_AU
dc.subjectTumor cellsen_AU
dc.titleA functional immune system is required for the systemic genotoxic effects of localized irradiationen_AU
dc.typeJournal Articleen_AU
dcterms.dateAccepted2018-11-29en_AU
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