Radiation-induced oral mucositis in mice: strain differences.

Abstract

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.