The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model.
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.
Vitolo
Joseph M
JM
Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland 20892, USA.
Cotrim
Ana P
AP
Sowers
Anastasia L
AL
Russo
Angelo
A
Wellner
Robert B
RB
Pillemer
Stanley R
SR
Mitchell
James B
JB
Baum
Bruce J
BJ
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
D000975:Antioxidants; D003497:Cyclic N-Oxides; D011837:Radiation-Protective Agents; D013113:Spin Labels; C001803:tempol