The Stable Nitroxide Tempol Facilitates Salivary Gland Protection during Head and Neck Irradiation in a Mouse Model

• Published in: Clinical cancer research Vol. 10; no. 5; pp. 1807 - 1812
• Main Authors: VITOLO, Joseph M, COTRIM, Ana P, SOWERS, Anastasia L, RUSSO, Angelo, WELLNER, Robert B, PILLEMER, Stanley R, MITCHELL, James B, BAUM, Bruce J
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.03.2004
• Subjects: Animals; Antineoplastic agents; Antioxidants - therapeutic use; Biological and medical sciences; Cyclic N-Oxides - therapeutic use; Disease Models, Animal; Female; Head and Neck Neoplasms - radiotherapy; Medical sciences; Mice; Mice, Inbred C3H; Pharmacology. Drug treatments; Radiation-Protective Agents - pharmacology; Radiotherapy - adverse effects; Salivary Glands - drug effects; Salivary Glands - radiation effects; Spin Labels; Tumors; Animal model; Vertebrata; Mammalia; Mouse; Digestive system; Rodentia; Irradiation; Head and neck; Salivary gland
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-03-0194

Purpose: 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. Experimental Design: 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 ∼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.