ORIGINAL RESEARCH ARTICLE Open Access X-Ray-Induced Damage to the Submandibular Salivary Glands in Mice: An Analysis of Strain-Specific Responses

Radiation therapy for head and neck cancers often causes xerostomia (dry mouth) by acutely damaging the sal-ivary glands through the induction of severe acute inflammation. By contrast, the mechanism underlying the X-ray-induced delayed salivary dysfunction is unknown and has attracted increasing attention. To identify and de-velop a mouse model that distinguishes the delayed from the acute effects, we examined three different mouse strains (C57BL/6, ICR, and ICR-nu/nu) that showed distinct T-cell activities to comparatively analyze their re-sponses to X-ray irradiation. Three strains were irradiated with X-rays (25 Gy), and functional changes of the sub-mandibular glands were examined by determining pilocarpine-induced saliva secretion. Structural changes were evaluated using histopathological and immunohistochemical examinations of CD3, cleaved poly (ADP-ribose) polymerase (PARP), and Bcl-xL. In C57BL/6 mice, the X-ray irradiation induced acute inflammation accompanied by severe inflammatory cell infiltration at 4 days postirradiation, causing substantial destruction and significant dysfunction at 2 weeks. Fibrotic repair was observed at 16 weeks. In ICR-nu/nu mice, the inflammation and organ destruction were much milder than in the other mice strains, but increased apoptotic cells and a significant re-duction in salivary secretion were observed at 4 and 8 weeks and beyond, respectively. These results suggest that in C57BL/6 mice, X-ray-induced functional and structural damage to the salivary glands is caused mainly by acute inflammation. By contrast, although neither acute inflammation nor organ destruction was observed in ICR-nu/ nu mice, apoptotic cell death preceded the dysfunction in salivary secretion in the later phase. These data sug-gest that the X-ray-irradiated ICR-nu/nu mouse may be a useful animal model for developing more specific ther-apeutic methods for the delayed dysfunction of salivary glands. Key words: apoptosis; inflammation; saliva; submandibular gland; T lymphocytes; X-ra