| 1217 Development of radiation-induced mucositis model with single and fractionated irradiation | ||
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A.P. COTRIM1, A. VOUTETAKIS1, Y. SAMUNI1, A. SOWERS2, J.B. MITCHELL2, and B.J. BAUM1, 1NIDCR NIH, Bethesda, MD, USA, 2NIH - NCI, bethesda, MD, USA Severe mucositis is not only a frequent (~97%) consequence of irradiation (IR) therapy in patients treated for head and neck cancer, but also one causing considerable morbidity. Objectives: We have evaluated two drugs for their ability to prevent the onset of IR-induced mucositis: the FDA-approved, yet still controversial agent, Amifostine, and the stable nitroxide Tempol, which we previously showed prevented IR-induced salivary hypofunction (Cotrim et al, Clin Cancer Res.2005). Methods: To test the potential of both radio-protectors, we developed a mouse model for IR-induced mucositis. The heads of C3H mice were exposed to a range of single (0-25Gy) IR doses or a regimen of fractionated IR doses (5x10.3Gy) after administration of either saline (control group), Amifostine [400 mg/kg, i.v.] or Tempol [275 mg/kg i.p.]. Animals were sacrificed and samples from both tongue and oral mucosa were obtained on days 0, 1, 3, 5, 7 and 10 post-IR for histolopathological evaluation. Results: A single dose >15 Gy led to erythema, which was first noticed at the base of the tongue on day 7. Upon staining with toluidine blue, ulcers at the base of the tongue became readily visible and their size was measured. Administration of Tempol did not prevent the ulcers from forming or diminish their size, while Amifostine treatment was apparently effective. The fractionated IR dose regimen resulted in severe ulcers that could not be prevented with either Amifostine or Tempol. Additionally, optical coherence tomographic (OCT) imaging was used throughout the experiment prior to sampling in an attempt to monitor IR-induced mucosal damage in a non-invasive manner (i.e., in real-time). OCT results were compared to histopathological findings and were found to be equally informative. Conclusion: Under single IR dose conditions, Amifostine treatment was beneficial. However, neither drug was useful to prevent IR damage with the present fractionated IR regimen. | ||
| Seq #129 - Clinical Diseases and Pathogenesis 3:30 PM-4:45 PM, Thursday, March 22, 2007 Ernest N. Morial Convention Center Exhibit Hall I2-J | ||
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