Abstract

The generation of a self-resolved radiation-induced oral mucositis (RIOM) mouse model using the highest possibly tolerable single ionizing radiation (RT) dose was needed in order to study RIOM management solutions. We used 10-week-old male BALB/c mice with average weight of 23 g for model production. Mice were treated with an orthovoltage X-ray irradiator to induce the RIOM ulceration at the intermolar eminence of the animal tongue. General anesthesia was injected intraperitoneally for proper animal immobilization during the procedure. Ten days after irradiation, a single RT dose of 10, 15, 18, 20, and 25 Gy generated a RIOM ulcer at the intermolar eminence (posterior upper tongue surface) with mean ulcer floor (posterior epithelium) heights of 190, 150, 25, 10, and 10 μm, respectively, compared to 200 μm in non-irradiated animals. The mean RIOM ulcer size % of the total epithelialized upper surface of the animal tongue was RT dose dependent. At day 10, the ulcer size % was 2, 5, 27, and 31% for 15, 18, 20, and 25 Gy RT, respectively. The mean relative surface area of the total epithelialized upper surface of the tongue was RT dose dependent, since it was significantly decreased to 97, 95, 88, and 38% with 15, 18, 20, and 25 Gy doses, respectively, at day 10 after RT. Subcutaneous injection of 1 mL of 0.9% saline/6 h for 24 h yielded a 100% survival only with 18 Gy self-resolved RIOM, which had 5.6 ± 0.3 days ulcer duration. In conclusion, we have generated a 100% survival self-resolved single-dose RIOM male mouse model with long enough duration for application in RIOM management research. Oral mucositis ulceration was radiation dose dependent. Sufficient hydration of animals after radiation exposure significantly improved their survival.

Highlights

  • Radiation-induced oral mucositis (RIOM) is a normal tissue injury side effect of ionizing radiation (RT) therapy with an 80% incidence in Head and Neck cancer patients [1, 2]

  • Radiation-induced oral mucositis ulceration was localized to the intermolar eminence of the animal tongue, which is located at the upper posterior surface of the tongue

  • The toluidine blue (TB)-stained RIOM ulceration was evident with all RT doses except 10 Gy, which produced a very limited epithelial loss at the eminence; it showed marked cellular infiltration similar to other RT doses

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Summary

Introduction

Radiation-induced oral mucositis (RIOM) is a normal tissue injury side effect of ionizing radiation (RT) therapy with an 80% incidence in Head and Neck cancer patients [1, 2]. A study had recorded a fractionated-dose RIOM ulcer duration mean of 2.9 ± 0.7 days [8] (M ± SD) and a single-dose RIOM ulcer duration of 2.0 ± 0.4 days (M ± SD) [15] For this reason, we were interested in generating a RIOM mouse model with longer inflammatory and ulcerative phase duration that will allow for better experimentation and investigation of many injury variables within the same experiment, especially in translational research. We were interested in generating a RIOM mouse model with longer inflammatory and ulcerative phase duration that will allow for better experimentation and investigation of many injury variables within the same experiment, especially in translational research This would lead to the generation of finer injury quantification and describing parameters to allow better RIOM injury control and therapy

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