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Published in: Clinical Oral Investigations 1/2004

01-03-2004 | Original Article

Early immunohistochemical and functional markers indicating radiation damage of the parotid gland

Authors: S. G. Hakim, H. Ch. Jacobsen, D. Hermes, H. Kosmehl, I. Lauer, R. Nadrowitz, P. Sieg

Published in: Clinical Oral Investigations | Issue 1/2004

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Abstract

In order to evaluate the correlation between functional impairment and changes in the expression pattern of immunohistochemical antibodies in the early phase of radiation-induced dysfunction of salivary glands, eight rabbits were scintigraphically examined prior to and 24 h after irradiation with 15 Gy. The parotid glands were studied using HE-staining, Ki-67, α-smooth muscle actin (ASMA) and tenascin-C antibodies at every scintigraphic examination. The results demonstrated a significant alteration in the 99mTc-pertechnetate uptake in all irradiated glands. HE-staining showed no relevant impairment of salivary gland tissue in this early phase. Immunohistochemically, we observed a marked re-distribution of ASMA and tenascin-C as well as a reduction of the proliferating rate of acinar cells. This immunohistochemical change correlated with the functional impairment manifested scintigraphically. This study proves the possibility to assess disorders of salivary gland function with immunohistological antibodies as early as 24 h after irradiation and yields the prerequisites to prove the effects of radioprotective agents on salivary gland tissues.
Literature
1.
go back to reference Albrecht HH, Creutzig H (1976) Salivary gland scintigraphy after radio-iodine therapy. Functional scintigraphy of the salivary gland after high dose radio-iodine therapy. ROFO Fortschr Geb Rontgenstr Nuklearmed 125:546–551PubMed Albrecht HH, Creutzig H (1976) Salivary gland scintigraphy after radio-iodine therapy. Functional scintigraphy of the salivary gland after high dose radio-iodine therapy. ROFO Fortschr Geb Rontgenstr Nuklearmed 125:546–551PubMed
2.
go back to reference Bartel-Friedrich S, Friedrich RE, Lautenschlager C, Holzhausen HJ (2000) Dose-response relationships and the effect of age and latency period on the expression profile of laminin in irradiated rat mandibular glands. Anticancer Res 20:5221–5228PubMed Bartel-Friedrich S, Friedrich RE, Lautenschlager C, Holzhausen HJ (2000) Dose-response relationships and the effect of age and latency period on the expression profile of laminin in irradiated rat mandibular glands. Anticancer Res 20:5221–5228PubMed
3.
go back to reference Blue PW, Jackson JH (1985) Stimulated salivary clearance of technetium-99m pertechnetate. J Nucl Med 26:308–311PubMed Blue PW, Jackson JH (1985) Stimulated salivary clearance of technetium-99m pertechnetate. J Nucl Med 26:308–311PubMed
4.
go back to reference Bohuslavizki KH, Klutmann S, Jenicke L, Brenner W, Feyerabend B, Henze E, Clausen M (1999) Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model. Int J Radiat Oncol Biol Phys 45:181–186PubMed Bohuslavizki KH, Klutmann S, Jenicke L, Brenner W, Feyerabend B, Henze E, Clausen M (1999) Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model. Int J Radiat Oncol Biol Phys 45:181–186PubMed
5.
go back to reference Dardick I, Rippstein P, Skimming L, Boivin M, Parks WR, Dairkee SH (1987) Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: histogenetic implications for salivary gland tumors. Oral Surg Oral Med Oral Pathol 64:703–715PubMed Dardick I, Rippstein P, Skimming L, Boivin M, Parks WR, Dairkee SH (1987) Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: histogenetic implications for salivary gland tumors. Oral Surg Oral Med Oral Pathol 64:703–715PubMed
6.
go back to reference Dreizen S, Brown LR, Handler S, Levy BM (1976) Radiation-induced xerostomia in cancer patients. Effect on salivary and serum electrolytes. Cancer 38:273–278PubMed Dreizen S, Brown LR, Handler S, Levy BM (1976) Radiation-induced xerostomia in cancer patients. Effect on salivary and serum electrolytes. Cancer 38:273–278PubMed
7.
go back to reference El-Mofty SK, Kahn AJ (1981) Early membrane injury in lethally irradiated salivary gland cells. Int J Radiat Biol Relat Stud Phys Chem Med 39:55–62PubMed El-Mofty SK, Kahn AJ (1981) Early membrane injury in lethally irradiated salivary gland cells. Int J Radiat Biol Relat Stud Phys Chem Med 39:55–62PubMed
8.
go back to reference Friedrich RE, Bartel-Friedrich S, Lautenschlager C, Holzhausen HJ, Moll R (2000) Dose response relations of collagen IV expression in irradiated submandibular gland of the rat. Mund Kiefer Gesichtschir 4:125–130CrossRefPubMed Friedrich RE, Bartel-Friedrich S, Lautenschlager C, Holzhausen HJ, Moll R (2000) Dose response relations of collagen IV expression in irradiated submandibular gland of the rat. Mund Kiefer Gesichtschir 4:125–130CrossRefPubMed
9.
go back to reference Garrett JR (1998) Myoepithelial activity in salivary glands. In: Garrett JR, Ekström J, Anderson LC (eds) Glandular mechanisms of salivary secretion. Karger, Basel, pp 132–152 Garrett JR (1998) Myoepithelial activity in salivary glands. In: Garrett JR, Ekström J, Anderson LC (eds) Glandular mechanisms of salivary secretion. Karger, Basel, pp 132–152
10.
go back to reference Gustafsson H, Aalto Y, Franzen L, Thornell LE, Henriksson R (1998) Effects of fractionated irradiation on the cytoskeleton and basal lamina in parotid glands—an immunohistochemical study. Acta Oncol 37:33–40CrossRefPubMed Gustafsson H, Aalto Y, Franzen L, Thornell LE, Henriksson R (1998) Effects of fractionated irradiation on the cytoskeleton and basal lamina in parotid glands—an immunohistochemical study. Acta Oncol 37:33–40CrossRefPubMed
11.
go back to reference Hakim SG, Lauer I, Kosmehl H, Sieg P (2002) The superficial mandibular gland of the rabbit: a new experimental model for scintigraphic evaluation of salivary glands. Int J Oral Maxillofac Surg 31:303–308CrossRefPubMed Hakim SG, Lauer I, Kosmehl H, Sieg P (2002) The superficial mandibular gland of the rabbit: a new experimental model for scintigraphic evaluation of salivary glands. Int J Oral Maxillofac Surg 31:303–308CrossRefPubMed
12.
go back to reference Heimann H, Coupland SE, Gochman R, Hellmich M, Foerster MH (2001) Alterations in expression of mucin, tenascin-c and syndecan-1 in the conjunctiva following retinal surgery and plaque radiotherapy. Graefes Arch Clin Exp Ophthalmol 239:488–495PubMed Heimann H, Coupland SE, Gochman R, Hellmich M, Foerster MH (2001) Alterations in expression of mucin, tenascin-c and syndecan-1 in the conjunctiva following retinal surgery and plaque radiotherapy. Graefes Arch Clin Exp Ophthalmol 239:488–495PubMed
13.
go back to reference Helman J, Turner RJ, Fox PC, Baum BJ (1987) 99mTc-pertechnetate uptake in parotid acinar cells by the Na+/K+/Cl- co-transport system. J Clin Invest 79:1310–1313PubMed Helman J, Turner RJ, Fox PC, Baum BJ (1987) 99mTc-pertechnetate uptake in parotid acinar cells by the Na+/K+/Cl- co-transport system. J Clin Invest 79:1310–1313PubMed
14.
go back to reference Jones PL, Jones FS (2000) Tenascin-C in development and disease: gene regulation and cell function. Matrix Biol 19:581–596CrossRefPubMed Jones PL, Jones FS (2000) Tenascin-C in development and disease: gene regulation and cell function. Matrix Biol 19:581–596CrossRefPubMed
15.
go back to reference Jones PL, Boudreau N, Myers CA, Erickson HP, Bissell MJ (1995) Tenascin-C inhibits extracellular matrix-dependent gene expression in mammary epithelial cells. Localization of active regions using recombinant tenascin fragments. J Cell Sci 108:519–527PubMed Jones PL, Boudreau N, Myers CA, Erickson HP, Bissell MJ (1995) Tenascin-C inhibits extracellular matrix-dependent gene expression in mammary epithelial cells. Localization of active regions using recombinant tenascin fragments. J Cell Sci 108:519–527PubMed
16.
go back to reference Jones PL, Crack J, Rabinovitch M (1997) Regulation of tenascin-C, a vascular smooth muscle cell survival factor that interacts with the alpha v beta 3 integrin to promote epidermal growth factor receptor phosphorylation and growth. J Cell Biol 139:279–293PubMed Jones PL, Crack J, Rabinovitch M (1997) Regulation of tenascin-C, a vascular smooth muscle cell survival factor that interacts with the alpha v beta 3 integrin to promote epidermal growth factor receptor phosphorylation and growth. J Cell Biol 139:279–293PubMed
17.
go back to reference Kohn WG, Ship JA, Atkinson JC, Patton LL, Fox PC (1992) Salivary gland 99mTc-scintigraphy: a grading scale and correlation with major salivary gland flow rates. J Oral Pathol Med 21:70–74PubMed Kohn WG, Ship JA, Atkinson JC, Patton LL, Fox PC (1992) Salivary gland 99mTc-scintigraphy: a grading scale and correlation with major salivary gland flow rates. J Oral Pathol Med 21:70–74PubMed
18.
go back to reference Liem IH, Olmos RA, Balm AJ, Keus RB, van Tinteren H, Takes RP, Muller SH, Bruce AM, Hoefnagel CA, Hilgers FJ (1996) Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours. Eur J Nucl Med 23:1485–1490PubMed Liem IH, Olmos RA, Balm AJ, Keus RB, van Tinteren H, Takes RP, Muller SH, Bruce AM, Hoefnagel CA, Hilgers FJ (1996) Evidence for early and persistent impairment of salivary gland excretion after irradiation of head and neck tumours. Eur J Nucl Med 23:1485–1490PubMed
19.
go back to reference Mossman KL (1983) Quantitative radiation dose-response relationships for normal tissues in man. II. Response of the salivary glands during radiotherapy. Radiat Res 95:392–398PubMed Mossman KL (1983) Quantitative radiation dose-response relationships for normal tissues in man. II. Response of the salivary glands during radiotherapy. Radiat Res 95:392–398PubMed
20.
go back to reference Riekki R, Jukkola A, Oikarinen A, Kallioinen M (2001) Radiation therapy induces tenascin expression and angiogenesis in human skin. Acta Derm Venereol 81:329–333CrossRefPubMed Riekki R, Jukkola A, Oikarinen A, Kallioinen M (2001) Radiation therapy induces tenascin expression and angiogenesis in human skin. Acta Derm Venereol 81:329–333CrossRefPubMed
21.
go back to reference Shintani S, Alcalde RE, Matsumura T, Terakado N (1997) Extracellular matrices expression in invasion area of adenoid cystic carcinoma of salivary glands. Cancer Lett 116:9–14CrossRefPubMed Shintani S, Alcalde RE, Matsumura T, Terakado N (1997) Extracellular matrices expression in invasion area of adenoid cystic carcinoma of salivary glands. Cancer Lett 116:9–14CrossRefPubMed
22.
go back to reference Shrestha P, Sumitomo S, Ogata K, Yamada K, Takai Y, Yang L, Mori M (1994) Immunoreactive tenascin in tumours of salivary glands: evidence for enhanced expression in tumour stroma and production by tumour cells. Eur J Cancer B Oral Oncol 30B: 393–399PubMed Shrestha P, Sumitomo S, Ogata K, Yamada K, Takai Y, Yang L, Mori M (1994) Immunoreactive tenascin in tumours of salivary glands: evidence for enhanced expression in tumour stroma and production by tumour cells. Eur J Cancer B Oral Oncol 30B: 393–399PubMed
23.
go back to reference Stephens LC, Ang KK, Schultheiss TE, King GK, Brock WA, Peters LJ (1986) Target cell and mode of radiation injury in rhesus salivary glands. Radiother Oncol 7:165–174PubMed Stephens LC, Ang KK, Schultheiss TE, King GK, Brock WA, Peters LJ (1986) Target cell and mode of radiation injury in rhesus salivary glands. Radiother Oncol 7:165–174PubMed
24.
go back to reference Streuli CH, Bissell MJ (1990) Expression of extracellular matrix components is regulated by substratum. J Cell Biol 110:1405–1415PubMed Streuli CH, Bissell MJ (1990) Expression of extracellular matrix components is regulated by substratum. J Cell Biol 110:1405–1415PubMed
25.
go back to reference Sunardhi-Widyaputra S, van Damme B (1993) Immunohistochemical expression of tenascin in normal human salivary glands and in pleomorphic adenomas. Pathol Res Pract 189:138–143PubMed Sunardhi-Widyaputra S, van Damme B (1993) Immunohistochemical expression of tenascin in normal human salivary glands and in pleomorphic adenomas. Pathol Res Pract 189:138–143PubMed
26.
go back to reference Talhouk RS, Bissell MJ, Werb Z (1992) Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol 118:1271–1282PubMed Talhouk RS, Bissell MJ, Werb Z (1992) Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol 118:1271–1282PubMed
27.
go back to reference van Acker F, Flamen P, Lambin P, Maes A, Kutcher GJ, Weltens C, Hermans R, Baetens J, Dupont P, Rijnders A, Maes A, van den Bogaert W, Mortelmans L (2001) The utility of SPECT in determining the relationship between radiation dose and salivary gland dysfunction after radiotherapy. Nucl Med Commun 22:225–231CrossRefPubMed van Acker F, Flamen P, Lambin P, Maes A, Kutcher GJ, Weltens C, Hermans R, Baetens J, Dupont P, Rijnders A, Maes A, van den Bogaert W, Mortelmans L (2001) The utility of SPECT in determining the relationship between radiation dose and salivary gland dysfunction after radiotherapy. Nucl Med Commun 22:225–231CrossRefPubMed
28.
go back to reference Vissink A, Kalicharan D, S-Gravenmade EJ, Jongebloed WL, Ligeon EE, Nieuwenhuis P, Konings AW (1991) Acute irradiation effects on morphology and function of rat submandibular glands. J Oral Pathol Med 20:449–456PubMed Vissink A, Kalicharan D, S-Gravenmade EJ, Jongebloed WL, Ligeon EE, Nieuwenhuis P, Konings AW (1991) Acute irradiation effects on morphology and function of rat submandibular glands. J Oral Pathol Med 20:449–456PubMed
Metadata
Title
Early immunohistochemical and functional markers indicating radiation damage of the parotid gland
Authors
S. G. Hakim
H. Ch. Jacobsen
D. Hermes
H. Kosmehl
I. Lauer
R. Nadrowitz
P. Sieg
Publication date
01-03-2004
Publisher
Springer-Verlag
Published in
Clinical Oral Investigations / Issue 1/2004
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-003-0249-9

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