title: X-Ray-Induced Damage to the Submandibular Salivary Glands in Mice: An Analysis of Strain-Specific Responses.
abstract: Radiation therapy for head and neck cancers often causes xerostomia (dry mouth) by acutely damaging the salivary 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 develop 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 responses to X-ray irradiation. Three strains were irradiated with X-rays (25 Gy), and functional changes of the submandibular 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 reduction 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 suggest that the X-ray-irradiated ICR-nu/nu mouse may be a useful animal model for developing more specific therapeutic methods for the delayed dysfunction of salivary glands.
authors: Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University , Niigata, Japan . ; Division of Periodontology, Department of Oral Biological Science, Institute of Medicine and Dentistry, Niigata University , Niigata, Japan .
authors: Mana
authors: M
authors: Kamiya
authors: Division of Oral Bioengineering, Department of Tissue Regeneration and Reconstitution, Institute of Medicine and Dentistry, Niigata University , Niigata, Japan . ; Advanced Research Center, The Nippon Dental University School of Life Dentistry at Niigata , Niigata, Japan .
authors: Tomoyuki
authors: T
authors: Kawase
authors: Department of Oral and Maxillofacial Radiology, The Nippon Dental University School of Life Dentistry at Niigata , Niigata, Japan .
authors: Kazuhide
authors: K
authors: Hayama
authors: Department of Oral and Maxillofacial Radiology, The Nippon Dental University School of Life Dentistry at Niigata , Niigata, Japan .
authors: Makoto
authors: M
authors: Tsuchimochi
authors: Division of Periodontology, Department of Oral Biological Science, Institute of Medicine and Dentistry, Niigata University , Niigata, Japan .
authors: Kazuhiro
authors: K
authors: Okuda
authors: Division of Periodontology, Department of Oral Biological Science, Institute of Medicine and Dentistry, Niigata University , Niigata, Japan .
authors: Hiromasa
authors: H
authors: Yoshie
keywords: T lymphocytes; X-ray; apoptosis; inflammation; saliva; submandibular gland