Spatio-temporal localization of HIF-1alpha and COX-2 during irradiation-induced oral mucositis in a rat model system.
PURPOSE: Oral mucositis is a common side effect of radiotherapy for head and neck cancer. The purpose of this study was to examine the significance of and the relationship between hypoxia inducible factor-1alpha (HIF-1alpha) and cyclooxygenase-2 (COX-2) gene expression and the corresponding protein levels in irradiated rat mucosa. MATERIAL AND METHODS: A Sprague-Dawley rat model of irradiation-induced oral mucositis was generated. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the HIF-1alpha and COX-2 mRNA level in rat buccal mucosa exposed to a fractionated irradiation regime. The Streptavidin-Biotin-Complex method was applied to delineate the in situ localization, intensity, and distribution of both proteins. The right buccal mucosa was not irradiated and used as control tissue. RESULTS: The RT-PCR analyses demonstrated that, upon irradiation, HIF-1alpha and COX-2 expression was significantly induced in the left buccal mucosa in contrast to control buccal mucosa. Based on immunohistochemical analyses, the HIF-1alpha and COX-2 level, in situ localization, and the type of cells exhibiting the highest HIF-1alpha and COX-2 amounts appear to correlate. CONCLUSIONS: The expression and protein levels of HIF-1alpha and COX-2 are substantially enhanced in irradiated rat mucosa and correlate with each other and with the severity of irradiation-induced oral mucositis.
Feng, C-J; Guo, J-B; Jiang, H-W; Zhu, S-X; Li, C-Y; Cheng, B; Chen, Y; Wang, H-Y
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