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Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, and Divisions of Oral Medicine, Oral and Maxillofacial Surgery and Dentistry, Brigham and Women’s Hospital and the Dana Farber Cancer Institute, 75 Francis Street, Boston, MA 02115; Ssonis{at}partners.org
Oral mucosal barrier injury (mucositis) is a frequent, painful, serious, dose-limiting toxicity associated with many anti-neoplastic drugs and radiation to the head and neck. Results of recent studies suggest that mucositis is the result of a complex series of interactive biological events that take place in the submucosa and epithelium. The nuclear transcription factor NF-
B has been implicated in the control of a broad range of biological responses, the activation of a large number of specific cellular genes, and the determination of the fate of cells exposed to ionizing radiation and anti-neoplastic drugs. Of particular importance to mucositis is the fact that NF-B regulates key elements in the apparent sequence that leads to normal tissue toxicity. Not the least of these is the effect that NF-B activation has on apoptosis. In particular, a paradox exists between the potential pro-apoptotic effect NF-B exerts on normal cells, and the anti-apoptotic and cytoprotective effect it causes in tumor cells. This paper provides a review of the structure and function of NF-B and speculates how its apparent enigmatic effect on normal and tumor cells may occur.
Key words. Nuclear factor-kappaB, mucosal injury, anti-neoplastic therapy
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