title: A rat model of radiation injury in the mandibular area.
abstract: BACKGROUND
  Radiation technology focuses on delivering the radiation as precisely as possible to the tumor, nonetheless both acute and long-term damage to surrounding normal tissue may develop. Injuries to the surrounding normal tissue after radiotherapy of head and neck cancer are difficult to manage. An animal model is needed to elucidate good treatment modalities. The aim of this study was to establish a rat model where a certain radiation dose gives reproducible tissue reactions in the mandibular area corresponding to injuries obtained in humans.
  
  
  METHODS
  The left mandible of male Sprague Dawley rats was irradiated by external radiotherapy (single fraction 15 Gy, total dose 75 Gy) every second week five times. Endpoint was six weeks after last radiation treatment, and the test group was compared to non-irradiated controls. Morphological alterations of the soft tissues, bone and tooth formation, as well as alterations of salivation, vascularity and collagen content were assessed. An unpaired, non-parametric Mann-Whitney test was used to compare the statistical differences between the groups.
  
  
  RESULTS
  Analysis of the soft tissues and mandible within the radiation field revealed severe unilateral alopecia and dermatitis of the skin, extensive inflammation of the submandibular gland with loss of serous secretory cells, hyperkeratinization and dense connective fiber bundles of the gingival tissue, and disturbed tooth development with necrosis of the pulp. Production of saliva and the vascularity of the soft tissues were significantly reduced. Furthermore, the collagen fibril diameter was larger and the collagen network denser compared to non-irradiated control rats.
  
  
  CONCLUSIONS
  We have established an animal model of radiation injury demonstrating physiological and histological changes corresponding to human radiation injuries, which can be used for future therapeutic evaluations.
authors.affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry University of Bergen, Serviceboks 7804, N-5020, Bergen, Norway. Tonje.Sonstevold@uib.no.
authors.forename: Tonje
authors.initials: T
authors.lastname: Sønstevold
authors.affiliation: The Gade Laboratory for Pathology, Department of Clinical Medicine, Faculty of Medicine and Dentistry, University of Bergen, Bergen, Norway. Anne.Johannessen@uib.no.
authors.forename: Anne Christine
authors.initials: AC
authors.lastname: Johannessen
authors.affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry University of Bergen, Serviceboks 7804, N-5020, Bergen, Norway. Linda.Stuhr@uib.no.
authors.forename: Linda
authors.initials: L
authors.lastname: Stuhr
mesh_terms: D000505:Alopecia / Q000209:etiology; D000818:Animals; D002610:Cheek / Q000098:blood supply / Q000473:pathology / Q000528:radiation effects; D003094:Collagen / Q000528:radiation effects; D003238:Connective Tissue / Q000528:radiation effects / Q000648:ultrastructure; D003790:Dental Pulp Necrosis / Q000209:etiology / Q000473:pathology; D005720:Gamma Rays / Q000009:adverse effects*; D005881:Gingiva / Q000098:blood supply / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D008334:Mandible / Q000473:pathology / Q000528:radiation effects*; D008410:Masticatory Muscles / Q000473:pathology / Q000528:radiation effects*; D058958:Organs at Risk / Q000528:radiation effects*; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000209:etiology*; D011855:Radiodermatitis / Q000209:etiology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012469:Salivary Glands / Q000473:pathology / Q000528:radiation effects*; D012472:Salivation / Q000528:radiation effects; D013997:Time Factors; D014070:Tooth / Q000528:radiation effects*; D014987:Xerostomia / Q000209:etiology / Q000473:pathology
chemical_list: D003094:Collagen