title: Local hypoxia in oral mucosa (mouse) during daily fractionated irradiation - Effect of pentoxifylline.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Comprehensive Cancer Center, Medical University/AKH Vienna, Austria.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Gruber
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hamedinger
authors.affiliation: Dept. Radiation Oncology/CD Lab. Med. Radiation Research for Radiation Oncology, Comprehensive Cancer Center, Medical University/AKH Vienna, Austria.
authors.forename: Eva
authors.initials: E
authors.lastname: Bozsaky
authors.affiliation: 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.
authors.forename: Margret
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Wolfram
authors.affiliation: Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Haagen
authors.affiliation: Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Habelt
authors.affiliation: Dept. Radiotherapy and Radiation Oncology, OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Technical University of Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Puttrich
authors.affiliation: 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.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dörr
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D065106:Demulcents / Q000494:pharmacology*; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D000860:Hypoxia / Q000209:etiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D008809:Mice, Inbred C3H; D009061:Mouth Mucosa / Q000528:radiation effects*; D010431:Pentoxifylline / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013280:Stomatitis / Q000150:complications / Q000517:prevention & control*; D014059:Tongue / Q000528:radiation effects
chemical_list: D065106:Demulcents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011837:Radiation-Protective Agents; D010431:Pentoxifylline
keywords: fractionated irradiation; hypoxia; mouse model; oral mucositis; pentoxifylline