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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

The effects of X-ray irradiation on the infiltration of CD3+ T cells and the construction of the submandibular salivary glands. (A) Immunohistochemical data of 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 immunohistochemical staining. The negative control is shown at the bottom left of the figure. Bar=20 μm. (B) Time course of the changes in CD3+ T-cell infiltration in the submandibular salivary glands. These immunohistochemical data were quantified and plotted in a graph. n=3. *p<0.05 compared with each result obtained at 0 day (nonirradiated control).
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f5: The effects of X-ray irradiation on the infiltration of CD3+ T cells and the construction of the submandibular salivary glands. (A) Immunohistochemical data of 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 immunohistochemical staining. The negative control is shown at the bottom left of the figure. Bar=20 μm. (B) Time course of the changes in CD3+ T-cell infiltration in the submandibular salivary glands. These immunohistochemical data were quantified and plotted in a graph. n=3. *p<0.05 compared with each result obtained at 0 day (nonirradiated control).

Mentions: The X-ray-induced infiltration of CD3+ T cells was examined immunohistochemically using an anti-CD3 antibody (Fig. 5). C57BL/6 mice are known to exhibit the dominant Th1 cell activity,20,21 whereas ICR-nu/nu mice genetically lack thymi and, consequently, functional T cells.22 It was therefore predicted that CD3+ T cells would infiltrate during acute inflammation in C57BL/6, but not in ICR-nu/nu mice. In C57BL/6 mice, the number of CD3+ T cells dramatically increased immediately after X-ray irradiation, followed by a rapid decrease to near basal levels within 16 weeks. In ICR mice, the number of CD3+ T cells that infiltrated during acute inflammation did not substantially decrease to basal levels within 16 weeks, but were sustained in chronic inflammation. In contrast, no significant infiltration of CD3+ T cells was observed in ICR-nu/nu mice. The immunohistochemical data were quantitated and plotted (Fig. 5, bottom). At day 4, the extent of CD3+ T-cell infiltration was C57BL/6 >> ICR>ICR-nu/nu, and at 16 weeks, it was ICR>C57BL/6>ICR-nu/nu. These data are consistent with the HE-staining data.


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)

The effects of X-ray irradiation on the infiltration of CD3+ T cells and the construction of the submandibular salivary glands. (A) Immunohistochemical data of 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 immunohistochemical staining. The negative control is shown at the bottom left of the figure. Bar=20 μm. (B) Time course of the changes in CD3+ T-cell infiltration in the submandibular salivary glands. These immunohistochemical data were quantified and plotted in a graph. n=3. *p<0.05 compared with each result obtained at 0 day (nonirradiated control).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: The effects of X-ray irradiation on the infiltration of CD3+ T cells and the construction of the submandibular salivary glands. (A) Immunohistochemical data of 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 immunohistochemical staining. The negative control is shown at the bottom left of the figure. Bar=20 μm. (B) Time course of the changes in CD3+ T-cell infiltration in the submandibular salivary glands. These immunohistochemical data were quantified and plotted in a graph. n=3. *p<0.05 compared with each result obtained at 0 day (nonirradiated control).
Mentions: The X-ray-induced infiltration of CD3+ T cells was examined immunohistochemically using an anti-CD3 antibody (Fig. 5). C57BL/6 mice are known to exhibit the dominant Th1 cell activity,20,21 whereas ICR-nu/nu mice genetically lack thymi and, consequently, functional T cells.22 It was therefore predicted that CD3+ T cells would infiltrate during acute inflammation in C57BL/6, but not in ICR-nu/nu mice. In C57BL/6 mice, the number of CD3+ T cells dramatically increased immediately after X-ray irradiation, followed by a rapid decrease to near basal levels within 16 weeks. In ICR mice, the number of CD3+ T cells that infiltrated during acute inflammation did not substantially decrease to basal levels within 16 weeks, but were sustained in chronic inflammation. In contrast, no significant infiltration of CD3+ T cells was observed in ICR-nu/nu mice. The immunohistochemical data were quantitated and plotted (Fig. 5, bottom). At day 4, the extent of CD3+ T-cell infiltration was C57BL/6 >> ICR>ICR-nu/nu, and at 16 weeks, it was ICR>C57BL/6>ICR-nu/nu. These data are consistent with the HE-staining data.

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