The Relationship Between Mucosal COX-2 Expression and Experimental Radiation-induced Mucositis

Objective: COX-2 expression has been associated with angiogenesis and consequently may have opposite effects on the radiosensitivity of normal and tumor tissue. The objective of this study was to evaluate the kinetics of COX-2 expression in normal oral mucosa following acute radiation exposure and to assess the relationship between COX-2 expression and the development of oral mucositis. Methods: Sixteen male Golden Syrian hamsters, aged 6-8 weeks, were anesthetized with ketamine/xylaxine. The left buccal cheek pouch was everted and radiated with a single dose of 40 Gy XRT while the remainder of the animal was protected with a lead shield. Four animals, selected at random, were sacrificed 2, 10, 16, and 21 days following XRT and the left buccal pouch was excised. The right buccal pouch was excised from 4 animals to serve as a control. Following fixation in 10% formalin, tissue was embedded in paraffin. Five-micron sections were obtained from representative areas of the pouch. COX-2 expression was determined following indirect immunohistochemical staining. Results: As expected, little or no COX-2 expression was observed in unirradiated tissue. In contrast, COX-2 expression was noted in radiated tissues as a function of time. Whereas little staining was present on day 2, sections obtained from hamsters on days 10 and 16 demonstrated staining of fibroblasts, endothelium, and selected epithelial cells. The intensity and distribution of staining was most notable on day 16, corresponding to peak mucositis severity. By day 21, COX-2 expression and mucositis severity both decreased. Conclusions: The timing of COX-2 expression in radiated mucosa suggests that it is not a primary driver of mucositis. Rather, cellular and molecular events triggered by RT proceed and may result in its expression. Theoretically, the biological effect of COX-2 expression may be related to an attempt at angiogenesis associated with wound healing. Supported by Pharmacia Inc.