title: The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model.
abstract: OBJECTIVE
  Radiotherapy is commonly used to treat a majority of patients with head and neck cancers. The long-term radiation-induced reduction of saliva output significantly contributes to the posttreatment morbidity experienced by these patients. The purpose of this study was to test the ability of the stable-free radical Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), an established radioprotector, to prevent radiation-induced salivary hypofunction in mice.
  
  
  METHODS
  The heads of C3H mice were exposed to a range of single radiation doses with or without an i.p. injection of 275 mg/kg Tempol 10 min before treatment. Salivary gland output was assessed 8 weeks postirradiation.
  
  
  RESULTS
  Radiation caused a dose-dependent reduction in salivary flow in this model. Tempol treatment alone significantly reduced radiation-induced salivary hypofunction. The combination of Tempol with mouth/nose shielding showed essentially complete radiation protection at 15 Gy and approximately 75% protection at 17.5 Gy.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that significant radioprotection of the salivary glands is possible with Tempol in C3H mice.
authors.affiliation: Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Vitolo
authors.forename: Ana P
authors.initials: AP
authors.lastname: Cotrim
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Sowers
authors.forename: Angelo
authors.initials: A
authors.lastname: Russo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wellner
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Pillemer
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Baum
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D051379:Mice; D008809:Mice, Inbred C3H; D011837:Radiation-Protective Agents / Q000494:pharmacology; D011878:Radiotherapy / Q000009:adverse effects; D012469:Salivary Glands / Q000187:drug effects / Q000528:radiation effects*; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D011837:Radiation-Protective Agents; D013113:Spin Labels; C001803:tempol