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X-Ray-Induced Damage to the Submandibular Salivary Glands in Mice: An Analysis of Strain-Specific Responses.

Kamiya M, Kawase T, Hayama K, Tsuchimochi M, Okuda K, Yoshie H - Biores Open Access (2015)

Bottom Line: By contrast, the mechanism underlying the X-ray-induced delayed salivary dysfunction is unknown and has attracted increasing attention.Three strains were irradiated with X-rays (25 Gy), and functional changes of the submandibular glands were examined by determining pilocarpine-induced saliva secretion.Fibrotic repair was observed at 16 weeks.

View Article: PubMed Central - PubMed

Affiliation: 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 .

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.

No MeSH data available.


Related in: MedlinePlus

Time course of morphological changes in the submandibular salivary glands in X-ray-irradiated mice (25 Gy). The salivary glands were retrieved at 4 days and 16 weeks postirradiation, and the paraffin sections were subjected to hematoxylin–eosin staining. Similar observations were obtained from two additional mice from each strain. Bar=20 μm.
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f4: Time course of morphological changes in the submandibular salivary glands in X-ray-irradiated mice (25 Gy). The salivary glands were retrieved at 4 days and 16 weeks postirradiation, and the paraffin sections were subjected to hematoxylin–eosin staining. Similar observations were obtained from two additional mice from each strain. Bar=20 μm.

Mentions: X-ray-induced acute and chronic inflammation was examined histologically using HE staining (Fig. 4). At day 4 in both C57BL/6 and ICR mice, X-ray irradiation caused acute inflammation with an increased infiltration of inflammatory cells, primarily T lymphocytes. Although inflammatory cells were abundant in C57BL/6 mice, they were observed in limited numbers around the intercalated ducts in ICR mice. These infiltrating cells were still present after the structural destruction of salivary glands at 16 weeks, indicating a shift to chronic inflammation in these mice. By contrast, no appreciable inflammatory response was observed in ICR-nu/nu mice, and the normal structure of salivary glands was preserved at 16 weeks.


X-Ray-Induced Damage to the Submandibular Salivary Glands in Mice: An Analysis of Strain-Specific Responses.

Kamiya M, Kawase T, Hayama K, Tsuchimochi M, Okuda K, Yoshie H - Biores Open Access (2015)

Time course of morphological changes in the submandibular salivary glands in X-ray-irradiated mice (25 Gy). The salivary glands were retrieved at 4 days and 16 weeks postirradiation, and the paraffin sections were subjected to hematoxylin–eosin staining. Similar observations were obtained from two additional mice from each strain. Bar=20 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4497710&req=5

f4: Time course of morphological changes in the submandibular salivary glands in X-ray-irradiated mice (25 Gy). The salivary glands were retrieved at 4 days and 16 weeks postirradiation, and the paraffin sections were subjected to hematoxylin–eosin staining. Similar observations were obtained from two additional mice from each strain. Bar=20 μm.
Mentions: X-ray-induced acute and chronic inflammation was examined histologically using HE staining (Fig. 4). At day 4 in both C57BL/6 and ICR mice, X-ray irradiation caused acute inflammation with an increased infiltration of inflammatory cells, primarily T lymphocytes. Although inflammatory cells were abundant in C57BL/6 mice, they were observed in limited numbers around the intercalated ducts in ICR mice. These infiltrating cells were still present after the structural destruction of salivary glands at 16 weeks, indicating a shift to chronic inflammation in these mice. By contrast, no appreciable inflammatory response was observed in ICR-nu/nu mice, and the normal structure of salivary glands was preserved at 16 weeks.

Bottom Line: By contrast, the mechanism underlying the X-ray-induced delayed salivary dysfunction is unknown and has attracted increasing attention.Three strains were irradiated with X-rays (25 Gy), and functional changes of the submandibular glands were examined by determining pilocarpine-induced saliva secretion.Fibrotic repair was observed at 16 weeks.

View Article: PubMed Central - PubMed

Affiliation: 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 .

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.

No MeSH data available.


Related in: MedlinePlus