W Dörr1, R Noack, K Spekl, C L Farrell. 1. Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Medizinische Fakultät Carl Gustav CArus der Technischen Universität, Dresden, Germany. doerr@rcs.urz.tu-dresden.de
Abstract
PURPOSE: 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. 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 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.
PURPOSE: The aim was to quantify the effect of recombinant humankeratinocyte growth factor (rhKGF) on acute oral mucositis induced by a single radiation 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 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.
Authors: Min Ho Jeong; Kwang Mo Yang; Dong Hyeok Jeong; Chang Geun Lee; Su Jung Oh; Soo Kyung Jeong; Ki Won Lee; Young Rae Jo; Wol Soon Jo Journal: J Radiat Res Date: 2014-01-07 Impact factor: 2.724
Authors: Andrea Hille; Susanne Grüger; Hans Christiansen; Hendrik A Wolff; Beate Volkmer; Jörg Lehmann; Wolfgang Dörr; Margret Rave-Fränk Journal: Radiat Environ Biophys Date: 2010-03-07 Impact factor: 1.925
Authors: C L Farrell; K L Rex; J N Chen; J V Bready; C R DiPalma; S A Kaufman; A Rattan; S Scully; D L Lacey Journal: Cell Prolif Date: 2002-08 Impact factor: 6.831