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CC BY-NC-ND 4.0 · Eur J Dent 2020; 14(03): 440-447
DOI: 10.1055/s-0040-1713705
Original Article

Distribution of Cytokeratin 17 in the Parenchymal Elements of Rat’s Submandibular Glands Subjected to Fractionated Radiotherapy

Sherif S. Hassan
1   Department of Oral Biology and Dental Anatomy, Faculty of Dentistry, Al-Azhar University (Assiut), Egypt and, Umm Al-Qura University, Saudi Arabia
,
Mahmoud A. Attia
2   Department of Oral Pathology, Faculty of Dentistry, Al-Azhar University, (Assiut), Egypt and Faculty of Applied Medical Science, Al-Baha University, Saudi Arabia
,
Alaa M. Attia
3   Department of Oral Medicine and Periodontology, Faculty of Dentistry, Al-Azhar University (Assiut), Egypt and Umm Al-Qura University, Saudi Arabia
,
Reda A. Nofal
4   Department of Oral and Maxillofacial Surgery Faculty of Dentistry, Al-Azhar University (Assiut), Egypt
,
Adel Fathi
5   Department of Pedodontics and Oral Health, Faculty of Dentistry, Al-Azhar University (Cairo), Egypt and Umm Al-Qura University, Saudi Arabia
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Abstract

Objectives The aim of this research was to study the intensity of cytokeratin 17 (CK17) in the parenchymal elements of rat’s submandibular salivary glands subjected to fractionated radiotherapy regimen that used for treatment of head and neck malignancy.

Materials and Methods Twenty male albino rats were divided into two equal groups (normal and irradiated). The irradiated group received a radiation dose of 5 Grays daily for 5 days using therapeutic X-ray beam. Six months later, submandibular gland was dissected out and prepared for both histological and immunohistochemical studies.

Results Submandibular gland of irradiated group showed two different types of histological alterations. The first alteration showed severe gland atrophy replaced by either fibrous or fatty tissues. In some sections, the gland exhibited proliferating activity in the form of profuse amounts of mitotic figures. Immunohistochemical examination of control glands displayed a mild cytoplasmic expression of CK17 of duct cells as well as serous acini. The staining pattern was either diffused or concentrated at the basal part of the cell with negative expression at its apical part.

Statistical Analysis Expression of CK17 in submandibular gland of irradiated group displayed a highly significant differences (P < 0.001) in both intercalated and striated ducts. Many serous acini displayed a highly significant differences (P < 0.001) whereas, mucous acini were negatively stained.

Conclusions The intensity and diffusion of CK17 expression in our results foretell the pathological effect of radiotherapy on the intermediate filaments of salivary gland parenchyma that interfered with production and/or secretion of saliva leading to xerostomia.

Keywords

fractionated - radiotherapy - submandibular - Cytokeratin 17


Publication History

Article published online:
26 June 2020

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  • References

  • 1 Dodds MW, Johnson DA, Yeh CK. Health benefits of saliva: a review. J Dent 2005; 33 (03) 223-233
    CrossrefPubMedSearch in Google Scholar
  • 2 Schipper RG, Silletti E, Vingerhoeds MH. Saliva as research material: biochemical, physicochemical and practical aspects. Arch Oral Biol 2007; 52 (12) 1114-1135
    CrossrefPubMedSearch in Google Scholar
  • 3 Sreebny L, Vissink A. Dry Mouth, the Malevolent Symptom: A Clinical Guide. Singapore: Wiley-Blackwell; 2010: 212-223
    Search in Google Scholar
  • 4 Funegard U. Fractionated Irradiation of Salivary Glands, Loss and Protection of Function. Tryckeri: Umea University; 1995: 6-85
    Search in Google Scholar
  • 5 Krishnan M, Tennavan A, Saraswathy S, Sekhri T, Singh AK, Nair V. Acute radiation-induced changes in Sprague-Dawley rat submandibular glands: a histomorphometric analysis. World J Oncol 2017; 8 (02) 45-52
    CrossrefPubMedSearch in Google Scholar
  • 6 Zajicek G, Schwartz-Arad D, Arber N, Michaeli Y. The streaming of the submandibular gland. II: parenchyma and stroma advance at the same velocity. Cell Tissue Kinet 1989; 22 (05) 343-348
    PubMedSearch in Google Scholar
  • 7 De Felice F, Tombolini M, Musella A, Marampon F, Tombolini V, Musio D. Radiation therapy and serum salivary amylase in head and neck cancer. Oncotarget 2017; 8 (52) 90496-90500
    CrossrefPubMedSearch in Google Scholar
  • 8 Marmary Y, Adar R, Gaska S. et al. Radiation-induced loss of salivary gland function is driven by cellular senescence and prevented by IL6 modulation. Cancer Res 2016; 76 (05) 1170-1180
    CrossrefPubMedSearch in Google Scholar
  • 9 Weng PL, Aure MH, Maruyama T, Ovitt CE. Limited regeneration of adult salivary glands after severe injury involves cellular plasticity. Cell Rep 2018; 24 (06) 1464-1470.e3
    CrossrefPubMedSearch in Google Scholar
  • 10 Jensen SB, Pedersen AM, Reibel J, Nauntofte B. Xerostomia and hypofunction of the salivary glands in cancer therapy. Support Care Cancer 2003; 11 (04) 207-225
    CrossrefPubMedSearch in Google Scholar
  • 11 Pringle S, Van Os R, Coppes RP. Concise review: adult salivary gland stem cells and a potential therapy for xerostomia. Stem Cells 2013; 31 (04) 613-619
    CrossrefPubMedSearch in Google Scholar
  • 12 Hancock PJ, Epstein JB, Sadler GR. Oral and dental management related to radiation therapy for head and neck cancer. J Can Dent Assoc 2003; 69 (09) 585-590
    PubMedSearch in Google Scholar
  • 13 Nguyen NP, Smith HJ, Sallah S. Evaluation and management of swallowing dysfunction following chemoradiation for head and neck cancer. Curr Opin Otolaryngol Head Neck Surg 2007; 15 (02) 130-133
    CrossrefPubMedSearch in Google Scholar
  • 14 Grundmann O, Fillinger JL, Victory KR, Burd R, Limesand KH. Restoration of radiation therapy-induced salivary gland dysfunction in mice by post therapy IGF-1 administration. BMC Cancer 2010; 10: 417-426
    CrossrefPubMedSearch in Google Scholar
  • 15 Wu VWC, Leung KY. A review on the assessment of radiation induced salivary gland damage after radiotherapy. Front Oncol 2019; 9: 1090
    CrossrefPubMedSearch in Google Scholar
  • 16 Chambers MS, Garden AS, Kies MS, Martin JW. Radiation-induced xerostomia in patients with head and neck cancer: pathogenesis, impact on quality of life, and management. Head Neck 2004; 26 (09) 796-807
    CrossrefPubMedSearch in Google Scholar
  • 17 Coppes RP, Roffel AF, Zeilstra LJ, Vissink A, Konings AW. Early radiation effects on muscarinic receptor-induced secretory responsiveness of the parotid gland in the freely moving rat. Radiat Res 2000; 153 (03) 339-346
    CrossrefPubMedSearch in Google Scholar
  • 18 Jensen SB, Vissink A, Limesand KH, Reyland ME. Salivary gland hypofunction and xerostomia in head and neck radiation patients. J Natl Cancer Inst Monogr 2019; 2019 (53) lgz016
    CrossrefPubMedSearch in Google Scholar
  • 19 Fox PC, van der Ven PF, Sonies BC, Weiffenbach JM, Baum BJ. Xerostomia: evaluation of a symptom with increasing significance. J Am Dent Assoc 1985; 110 (04) 519-525
    CrossrefPubMedSearch in Google Scholar
  • 20 El-Mofty SK, Kahn AJ. Early membrane injury in lethally irradiated salivary gland cells. Int J Radiat Biol Relat Stud Phys Chem Med 1981; 39 (01) 55-62
    CrossrefSearch in Google Scholar
  • 21 Stephens LC, King GK, Peters LJ, Ang KK, Schultheiss TE, Jardine JH. Acute and late radiation injury in rhesus monkey parotid glands. Evidence of interphase cell death. Am J Pathol 1986; 124 (03) 469-478
    PubMedSearch in Google Scholar
  • 22 Robar JL, Day A, Clancey J. et al. Spatial and dosimetric variability of organs at risk in head-and-neck intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 2007; 68 (04) 1121-1130
    CrossrefPubMedSearch in Google Scholar
  • 23 Saad S, Sohair S. Tumor Markers. 1st ed. London, New York, Tokyo, Madras: Chapman & Hall, Poka Raton Florida; 1998: 1-16
    Search in Google Scholar
  • 24 Bancroft J, Gamble M. Theory and Practice of Histological Techniques. 5th ed. London, NY: Churchill Livingstone; 2002: 593-598
    Search in Google Scholar
  • 25 Franke WW, Schiller DL, Moll R. et al. Diversity of cytokeratins. Differentiation specific expression of cytokeratin polypeptides in epithelial cells and tissues. J Mol Biol 1981; 153 (04) 933-959
    CrossrefPubMedSearch in Google Scholar
  • 26 Sozmen M, Brown PJ, Eveson JW. Cytokeratin immunostaining in normal dog major and minor salivary glands. Vet Res 1998; 29 (05) 457-465
    PubMedSearch in Google Scholar
  • 27 Burns BF, Dardick I, Parks WR. Intermediate filament expression in normal parotid glands and pleomorphic adenomas. Virchows Arch A Pathol Anat Histopathol 1988; 413 (02) 103-112
    CrossrefPubMedSearch in Google Scholar
  • 28 Bartel-Friedrich S, Friedrich R, Lautenschlager C, Moll R, Holzhausen H. Dose-response relationships on the expression profile of cytokeratin and vimentin in rats following fractionated irradiation. Anticancer Res 2000; 20: 4917-4926
    Search in Google Scholar
  • 29 Bartel-Friedrich S, Friedrich RE, Moll R, Lautenschläger C. Immunohistochemical detection of cytokeratins in the irradiated rat mandibular gland. Anticancer Res 1999; 19 (4A) 2405-2409
    Search in Google Scholar
  • 30 Emmerson E, May AJ, Berthoin L. et al. Salivary glands regenerate after radiation injury through SOX2-mediated secretory cell replacement. EMBO Mol Med 2018; 10 (03) 1-18
    CrossrefPubMedSearch in Google Scholar
  • 31 Hosseinimehr SJ. Trends in the development of radioprotective agents. Drug Discov Today 2007; 12 (19-20) 794-805
    CrossrefPubMedSearch in Google Scholar
  • 32 Hiramatsu Y, Nagler RM, Fox PC, Baum BJ. Rat salivary gland blood flow and blood-to-tissue partition coefficients following X-irradiation. Arch Oral Biol 1994; 39 (01) 77-80
    CrossrefPubMedSearch in Google Scholar
  • 33 Spraggs PD, Rose DS, Grant HR, Gallimore AP. Post-irradiation carcinosarcoma of the parotid gland. J Laryngol Otol 1994; 108 (05) 443-445
    CrossrefPubMedSearch in Google Scholar
  • 34 Fajardo LF, Berthrong M. Radiation injury in surgical pathology. Part III. Salivary glands, pancreas and skin. Am J Surg Pathol 1981; 5 (03) 279-296
    CrossrefPubMedSearch in Google Scholar
  • 35 Gustafsson H, Aalto Y, Franzén L, Thornell LE, Henriksson R. Effects of fractionated irradiation on the cytoskeleton and basal lamina in parotid glands—an immunohistochemical study. Acta Oncol 1998; 37 (01) 33-40
    CrossrefPubMedSearch in Google Scholar
  • 36 Bonan PR, Kaminagakura E, Pires FR, Vargas PA, Almeida OP. Cytokeratin expression in initial oral mucositis of head and neck irradiated patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006; 101 (02) 205-211
    CrossrefPubMedSearch in Google Scholar