Abstract:

Objective

To improve the existing animal models （mice， rats， and hamsters）for radiotherapy-induced oral mucositis （RTOM）， thereby establish a radiotherapy-induced glossitis（RTG） Sprague-Dawley （SD） rat model.

Methods

A cone-shaped lead device was designed in our laboratory and used to limit radiation exposure to a 1 cm × 1 cm area of a rat's local dorsal anterior tongue.This area was exposed to a single 30 Gy dose of X-ray radiation in six rats using the following experimental parameters： an accelerating voltage of 220 V， an operating current of 12 mA， a source-skin distance of 40 cm， an irradiation field of 10 cm × 15 cm， a 4 mm lead filter， and an absorbed dosage rate of 100.75 cGy/min.The general conditions of the irradiated rats， such as body-weight and behavior， were observed.The oral mucositis indices （OMI） of the RTG rats were measured daily using a previously reported scoring system.Histological changes in the irradiated tissues were assayed by H&E staining.

Results

No significant changes were clinically observed 3 to 4 days after the 30 Gy radiation dose was applied.According to microscopic analyses， the epithelial lamina was observed to be intact and partial epithelial proliferation was visible.There was a marked increase in the thickness of the prickle cell layer with very little inflammatory cell infiltration.Capillary extension and engorgement were observed.Five to 6 days after irradiation， punctuation and confluenced redness of the irradiated tongue mucosa were observed.Histologically， the small blood vessels in the submucosal lamina propria were observed to have become more extensive and engorged， and the vessel walls had become thin.More infiltrating cells were observable， the epithelial layer became more attenuated， necrosis and exfoliation of the squamous cells appeared， and the formation of an ulcerative lesion could be observed at the end of this stage.Seven to 8 days after irradiation， scattered ulcerative lesions could be observed with the naked eye.Furthermore， more necrosis and exfoliation of the squamous cells， a large number of infiltrating cells， and capillary extension and engorgement could be observed by optical microscopy.Nine to 12 days after irradiation， the exfoliated epithelial layer was observed to have formed an ulcerative lesion.Twelve to 14 days after irradiation， aggravated ulcerative lesions consisting of pseudomembranous filament exudates could be observed.Fourteen days after irradiation， the entire irradiated area had become a coherent ulcer.At this point， the structure of the epithelium had become completely disaggregated， forming deep， microscopic ulcerative lesions.Twenty-one days after irradiation， the periphery of the ulcer was observed to have begun to heal， and granulation tissue could be observed at the bottom of the ulceration.Twenty-eight to 35 days after irradiation， the irradiated area was observed to have undergone gradual healing.At this point， the epithelial structure presented again， but the epithelium was very thin.

Conclusions

An RTG animal model was successfully established in SD rats， which provides a new research platform for the study of RTOM pathogenesis.

Key words: Radiotherapy, Oral mucositis, Glossitis, Animal model