Biomedical subjects

K Spekl

Publications and source records attributed to K Spekl.

3 recordsLinked to original sources

PubMed2002

Radiation-induced oral mucositis in mice: strain differences.

The present study was initiated to investigate strain differences in oral mucosal radiosensitivity in mice with regard to induction of clinically manifest ulceration. Mouse ventral tongue epithelium was used as an established animal model for radiobiological studies of radiation-induced mucositis. Mice from two different strains, C3H/Neu (n = 40) from the Dresden colony, and B6D2F1 (n = 50) from the Harlan/Winkelmann UK colony were subjected to irradiation of tongue mucosa. Graded single doses were applied to a 3 x 3 mm2 test field in the centre of the lower tongue with 25 kV X-rays in order to generate full dose-effect curves for acute mucosal ulceration, as a clinically relevant reaction. For both groups, dose-effect curves were computed by logit analysis; comparison of the curves was by maximum-likelihood chi2 test. In addition, the time course of ulceration, i.e. latent time and individual ulcer duration, was analysed. In both mouse strains, a well-defined dose effect was observed. The ED50 values, i.e. the doses at which ulceration is expected in 50% of the animals irradiated, and their standard deviation sigma, calculated by logit analysis, can be used to describe radiosensitivity. The ED50 was 11.0 +/- 3.4 Gy (95% confidence interval (7.2; 15.4), P for dose dependence: 0.014) and 13.4 +/- 3.6 Gy (95% confidence interval (10.6; 16.1), P for dose dependence: 0.0002) in C3H and BDF1 mice, respectively. Hence, oral mucosa in BDF1 mice was found to be marginally more radioresistant (P = 0.1). The latent time to ulceration, i.e. the time between irradiation and first diagnosis of ulcer, was 11.6 +/- 0.2 days (mean +/- SEM, n = 18) in C3H mice and 5.6 +/- 0.1 days (n = 27) in BDF1 mice (P = 0.0001). Both were independent of dose (PC3H = 0.94, PBDF1 = 0.33) and hence were calculated for all responding animals of the respective strain. Ulcer duration was 2.8 +/- 0.2 days and 2.4 +/- 0.1 days in C3H and B6 mice, respectively, and was also independent of dose (PC3H = 0.25, PBDF1 = 0.99), but was dependent on the mouse strain (P = 0.036). In conclusion, no statistically significant difference in oral mucosal radiosensitivity was observed between the mouse strains. This, however, may be attributed to the small number of animals used per dose group. The time course data, with a shorter latency and ulcer duration in BDF1 mice, are in good accordance with the higher proliferation rates reported for oral mucosa in this mouse strain.

Animals↗

PubMed2002

The effect of keratinocyte growth factor on healing of manifest radiation ulcers in mouse tongue epithelium.

The purpose of this study was to examine the effect of recombinant human keratinocyte growth factor (rHuKGF) on clinically manifest acute oral mucositis. The animal model utilized in this investigation was ventral tongue epithelium of C3H/Neu mice. In a first experiment, graded single doses were applied in order to define dose effect and time course of acute mucosal ulceration, as a clinically relevant endpoint. Irradiation was given to a 3 x 3 mm2 test field in the centre of the ventral tongue with 25 kV X-rays. A single dose of 18 Gy, i.e. a dose after which ulceration is expected in more than 99% of the animals, was applied in subsequent experiments. In the study group of 20 animals, rHuKGF was applied at a daily dose of 5 mg/kg subcutaneously from the time of first diagnosis of ulcer for a maximum of 5 days. In the control group, phosphate-buffered saline was used as a placebo. The time course of ulceration, i.e. individual ulcer duration, was analysed in both the control group without rHuKGF and the study group. Irradiation with graded single doses yielded an ED50 of 11.5 +/- 0.7 Gy (logit analysis). In responding animals, the latent time to first diagnosis of ulceration and the individual ulcer duration were independent of dose. Mean latency (+/- standard deviation) was 10.5 +/- 0.5 days, mean ulcer duration 3.9 +/- 0.6 days for doses 11, 13 and 16 Gy. After a dose of 18 Gy, 39 animals developed ulceration after a mean latency of 9.3 +/- 0.3 days (control and KGF-treated). The average ulcer duration was 4.2 +/- 0.9 days in the placebo group and 4.8 +/- 0.8 days in the KGF group (P = 0.02). We conclude that when rHuKGF treatment is delayed until radiation-induced ulcers are manifest, the therapeutic activity previously reported with other treatment schedules was not observed and there was a slight prolongation of duration of ulceration. These data suggest that during tumour radiotherapy, effective rHuKGF therapy schedules should include administration before the onset of ulcerative mucositis.

Animals↗

PubMed2001

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

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.

Animals↗