Modification of oral mucositis by keratinocyte growth factor: single radiation exposure.
OBJECTIVE
The aim was to quantify the effect of recombinant human keratinocyte growth factor (rhKGF) on acute oral mucositis induced by a single radiation dose, simulating accidental radiation exposure.


METHODS
Tongue epithelium of the C3H/Neu mouse was irradiated with graded single doses of 25 kV X-rays to a 3 x 3 mm2 area in the centre of the lower tongue surface. Acute mucosal ulceration, as a clinically relevant reaction, was used as the quantal endpoint for dose response analyses by probit analysis. As a secondary endpoint the time-course, i.e. time to first diagnosis of ulcer (latent time) and individual ulcer duration, was analysed. KGF was applied before, after or in combination before and after radiation exposure.


RESULTS
Administration of KGF in all protocols resulted in a significant reduction 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 pronounced when KGF was applied after irradiation. In all protocols where KGF was given after irradiation, a significant shortening of the latent time to ulceration 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 represents a promising approach for the effective management of acute radiation reactions in oral, gastrointestinal and cutaneous epithelia after radiation exposure.
Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Medizinische Fakultät Carl Gustav CArus der Technischen Universität, Dresden, Germany. doerr@rcs.urz.tu-dresden.de
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Dörr
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Noack
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Spekl
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Farrell
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009061:Mouth Mucosa / Q000187:drug effects* / Q000528:radiation effects*; D019226:Oral Ulcer / Q000188:drug therapy / Q000209:etiology; D011833:Radiation Injuries, Experimental / Q000150:complications / Q000188:drug therapy*; D011930:Reaction Time / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D014059:Tongue / Q000187:drug effects / Q000528:radiation effects
C496454:Fgf7 protein, mouse; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors