Modification of oral mucositis by keratinocyte growth factor: single radiation exposure

Purpose: The aim was to quantify the effect of recombinant human keratinocy te growth factor (rhKGF) on acute oral mucositis induced by a single radiat ion dose, simulating accidental radiation exposure. Material and methods: Tongue epithelium of the C3H/Neu mouse was irradiated with graded single doses of 25 kV X-rays to a 3 x 3 mm(2) ar ea in the cen tre of the lower tongue surface. Acute mucosal ulceration, as a clinically relevant reaction, was used as the quantal endpoint for dose-response analy ses by probit analysis. As a secondary endpoint the time-course, i.e. time to first diagnosis of ulcer (latent lime) and individual ulcer duration, wa s analysed. KGF was applied before, after or in combination before and afte r radiation exposure. Results: Administration of KGF in all protocols resulted in a significant r eduction of the incidence of oral mucosal ulceration, as illustrated by an increase in iso-effective dose from 10.9 to 24.9 Gy; the corresponding dose -modification factors ranged between 1.7 and 2.3. The effect was most prono unced when KGF was applied after irradiation. In all protocols where KGF wa s given after irradiation, a significant shortening of the latent time to u lceration from 11 to 6-8 days was observed. Conclusions: The mechanisms underlying the amelioration of the oral mucosal response to single-dose irradiation remain unclear. However, KGF represent s a premising approach for the effective management of acute radiation reac tions in oral, gastrointestinal and cutaneous epithelia after radiation exp osure.