TRANSFORMING GROWTH FACTOR-BETA-3 MEDIATED MODULATION OF CELL CYCLINGAND ATTENUATION OF 5-FLUOROURACIL INDUCED ORAL MUCOSITIS

Mucositis is a common, dose-limiting complication in patients receivin g cancer chemotherapy, which derives from damage to the epithelial cel l layer. We have shown that transforming growth factor-beta 3 (TGF-bet a 3) negatively regulates epithelial cell proliferation and reduces th e incidence of oral mucositis. Here, we report the findings of a large study examining the effects of TGF-beta 3 administration in a hamster model on oral epithelial cell cycling in vivo, on oral mucositis, on weight retention and on survival. Topical application of TGF-beta 3 to the buccal mucosa significantly reduced basal cell proliferation, as measured by proliferating cell. nuclear antigen (PCNA) immunohistochem istry and DNA ploidy. Administration of topical TGF-beta 3 prior to ch emotherapy with 5-fluorouracil (5-FU) significantly reduced the severi ty of mucositis with respect to time, reduced chemotherapy-associated weight loss and increased survival. (C) 1997 Elsevier Science Ltd. All rights reserved.