Sylvia Gruber1, Daniel Hamedinger2, Eva Bozsaky1, Margret Schmidt3, Kathrin Wolfram4, Julia Haagen4, Bettina Habelt4, Martin Puttrich4, Wolfgang Dörr5. 1. Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Comprehensive Cancer Center, Medical University/AKH Vienna, Austria. 2. Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Comprehensive Cancer Center, Medical University/AKH Vienna, Austria; Department of Radiation Oncology, Krankenhaus der Barmherzigen Schwestern Linz, Austria. 3. Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, Germany; German Cancer Consortium (DKTK) partner site Dresden and German Cancer Center (DKFZ) Heidelberg, Germany. 4. Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, Germany. 5. Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Comprehensive Cancer Center, Medical University/AKH Vienna, Austria; Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, Germany; German Cancer Consortium (DKTK) partner site Dresden and German Cancer Center (DKFZ) Heidelberg, Germany. Electronic address: Wolfgang.Doerr@meduniwien.ac.at.
Abstract
PURPOSE: A significant reduction of radiation-induced oral mucositis by systemic application of pentoxifylline has been demonstrated in a mouse tongue model. However, the underlying mechanisms remain unclear. The present study focuses on the development of local hypoxia in mouse tongue during daily fractionated irradiation and a potential modulation by pentoxifylline. MATERIALS AND METHODS: Daily fractionated irradiation with 5×3Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 3 animals per day were sacrificed between day 0 and 14. Pentoxifylline (15mg/kg, s.c.) was administered daily from day -5 to the day before the mice were sacrificed. The expression of intrinsic hypoxia markers HIF-1α and GLUT1 in the epithelium of the lower tongue surface was analysed by immunohistochemistry in 3 animals per day; the percentage of positive epithelial cells and the staining intensity were analysed as endpoints. RESULTS: Compared to untreated control tissue, fractionated irradiation resulted in a progressive increase in the expression of both hypoxia markers. This effect was significantly reduced by pentoxifylline. CONCLUSION: An early onset of local hypoxia occurs during fractionated irradiation in mouse tongue epithelium. The effect is markedly reduced by the mucoprotective agent pentoxifylline, suggesting a mucositis-promoting role of hypoxia; this, however, deserves further investigation.
PURPOSE: A significant reduction of radiation-induced oral mucositis by systemic application of pentoxifylline has been demonstrated in a mouse tongue model. However, the underlying mechanisms remain unclear. The present study focuses on the development of local hypoxia in mouse tongue during daily fractionated irradiation and a potential modulation by pentoxifylline. MATERIALS AND METHODS: Daily fractionated irradiation with 5×3Gy/week (days 0-4, 7-11) was given to the snouts of mice. Groups of 3 animals per day were sacrificed between day 0 and 14. Pentoxifylline (15mg/kg, s.c.) was administered daily from day -5 to the day before the mice were sacrificed. The expression of intrinsic hypoxia markers HIF-1α and GLUT1 in the epithelium of the lower tongue surface was analysed by immunohistochemistry in 3 animals per day; the percentage of positive epithelial cells and the staining intensity were analysed as endpoints. RESULTS: Compared to untreated control tissue, fractionated irradiation resulted in a progressive increase in the expression of both hypoxia markers. This effect was significantly reduced by pentoxifylline. CONCLUSION: An early onset of local hypoxia occurs during fractionated irradiation in mouse tongue epithelium. The effect is markedly reduced by the mucoprotective agent pentoxifylline, suggesting a mucositis-promoting role of hypoxia; this, however, deserves further investigation.
Authors: J Bowen; N Al-Dasooqi; P Bossi; H Wardill; Y Van Sebille; A Al-Azri; E Bateman; M E Correa; J Raber-Durlacher; A Kandwal; B Mayo; R G Nair; A Stringer; K Ten Bohmer; D Thorpe; R V Lalla; S Sonis; K Cheng; S Elad Journal: Support Care Cancer Date: 2019-07-08 Impact factor: 3.603
Authors: Jon Kirk; Nirav Shah; Braxton Noll; Craig B Stevens; Marshall Lawler; Farah B Mougeot; Jean-Luc C Mougeot Journal: Support Care Cancer Date: 2018-02-23 Impact factor: 3.603