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Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model
Title: | Radiation-induced nitric oxide mitigates tumor hypoxia and radioresistance in a murine SCCVII tumor model |
Authors: | Nagane, Masaki Browse this author | Yasui, Hironobu Browse this author →KAKEN DB | Yamamori, Tohru Browse this author →KAKEN DB | Zhao, Songji Browse this author →KAKEN DB | Kuge, Yuji Browse this author →KAKEN DB | Tamaki, Nagara Browse this author →KAKEN DB | Kameya, Hiromi Browse this author | Nakamura, Hideo Browse this author →KAKEN DB | Fujii, Hirotada Browse this author →KAKEN DB | Inanami, Osamu Browse this author →KAKEN DB |
Keywords: | Ionizing radiation | Tumor reoxygenation | Electron spin resonance | Nitric oxide |
Issue Date: | 2-Aug-2013 |
Publisher: | Elsevier |
Journal Title: | Biochemical and biophysical research communications |
Volume: | 437 |
Issue: | 3 |
Start Page: | 420 |
End Page: | 425 |
Publisher DOI: | 10.1016/j.bbrc.2013.06.093 |
PMID: | 23831468 |
Abstract: | Tumor hypoxia, which occurs mainly as a result of inadequate tissue perfusion in solid tumors, is a well-known challenge for successful radiotherapy. Recent evidence suggests that ionizing radiation (IR) upregulates nitric oxide (NO) production and that IR-induced NO has the potential to increase intratumoral circulation. However, the kinetics of NO production and the responsible isoforms for NO synthase in tumors exposed to IR remain unclear. In this study, we aimed to elucidate the mechanism by which IR stimulates NO production in tumors and the effect of IR-induced NO on tumor radiosensitivity. Hoechst33342 perfusion assay and electron spin resonance oxymetry showed that IR increased tissue perfusion and pO(2) in tumor tissue. Immunohistochemical analysis using two different hypoxic probes showed that IR decreased hypoxic regions in tumors; treatment with a nitric oxide synthase (NOS) inhibitor, L-NAME, abrogated the effects of IR. Moreover, IR increased endothelial NOS (eNOS) activity without affecting its mRNA or protein expression levels in SCCVII-transplanted tumors. Tumor growth delay assay showed that L-NAME decreased the anti-tumor effect of fractionated radiation (10 Gy x 2). These results suggested that IR increased eNOS activity and subsequent tissue perfusion in tumors. Increases in intratumoral circulation simultaneously decreased tumor hypoxia. As a result, IR-induced NO increased tumor radiosensitivity. Our study provides a new insight into the NO-dependent mechanism for efficient fractionated radiotherapy. (C) 2013 Elsevier Inc. All rights reserved. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/53265 |
Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 稲波 修
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