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Multifocal Ductal Cell Hyperplasia in the Submandibular Salivary Glands of Wistar Rats Chronically Treated with a Novel Steroidal Compound
Eveline P.C.T. De Rijk
Organon, Department of Toxicology and Drug Disposition, 5340 BH Oss, The Netherlands, eveline.derijk{at}organon.com
Wilma T.M. Ravesloot
Organon, Department of Toxicology and Drug Disposition, 5340 BH Oss, The Netherlands
Theo G.M. Hafmans
University of Nijmegen, Department of Biochemistry, 6500 HB Nijmegen, The Netherlands
Eric Van Esch
Organon, Department of Toxicology and Drug Disposition, 5340 BH Oss, The Netherlands
A high incidence of multifocal ductal hyperplasia was observed in the submandibular salivary gland of rats treated for 26 weeks with a high dose of a novel synthetic steroid with combined estrogenic and progestagenic properties. Hyperplastic foci consisted of microcystic duct-like structures lined by a single or multilayered epithelium, sometimes showing a tendency towards a cribiform growth pattern. The hyperplastic ducts were embedded in a collagen-rich stroma and surrounded by numerous myoepithelial cells. Immunohistochemical methods used for the detection of estrogen- and progesterone receptors revealed that progesterone receptors were abundantly present in the nucleus of epithelial cells within the lesions, exclusively. Estrogen receptors could not be detected in both the normal tissue and hyperplasic foci. The morphological, ultrastructural, and immunohistochemical characteristics strongly suggest that these hyperplastic lesions originated from the intercalated ducts. The rodent-specific granular duct cell was not involved in the pathogenesis as was clearly demonstrated by the lack of immunoreactive epidermal growth factor within the lesions. Lesions were not observed in studies with progestagens and estrogens alone or with other combined estrogen/progestagen compounds, suggesting that the specific ratio of estrogenic and progestagenic activity of the present steroid had played an important role in the development of ductal hyperplasia in this study. Lesions of the intercalated ducts, as described in this study, have not been reported before in the literature.
Key Words: Rat • submandibular salivary gland • hyperplasia • intercalated duct • progestagen • estrogen • histopathology • immunohistochemistry • electron microscopy.
References
- Azumi N., Battifora H. (1987). The cellular composition of adenoid cystic carcinoma. An immunohistochemical study. Cancer 60: 1589—1598.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Bancroft JD, Stevens A. (1996). Hale's dialysed iron technique. In: Theory and Practice of Histological Techniques, Bancroft JD, Stevens A (eds). Churchill Livingstone, New York, pp 194—195.
- Barka T. (1980). Biologically active polypeptides in submandibular glands. J Histoch Cytochem 28: 836—859.[Abstract]
- Batsakis JG, Kraemer B., Sciubba JJ (1983). The pathology of head and neck tumors: The myoepithelial cell and its participation in salivary gland neoplasia, part 17. Head Neck Surg 5: 222—233.[Web of Science][Medline]
[Order article via Infotrieve]
- Burek JD (1976). Pathology of Aging Rats. CRC Press Inc, Boca Raton, FL, p 75.
- Campbell PS, Ben-Aryeh H., Swanson KA (1990). Differential distribution of an estrogen receptor in the submandibular and parotid glands of female rats. Endocr Res 16(3): 333—345.[Web of Science][Medline]
[Order article via Infotrieve]
- Capen CC, DeLellis RA, Yarrington JT (1991). Endocrine system. In: Handbook of Toxicologic Pathology, Haschek WM, Rousseaux CG (eds). Academic Press, San Diego, pp 675—751.
- Creasy DM, Foster PMD (1991). Male reproductive system. In: Handbook of Toxicologic Pathology, Haschek WM, Rousseaux CG (eds). Academic Press, San Diego, pp 829—887.
- Dardick I., Byard RW, Carnegie JA (1990). A review of the proliferative capacity of major salivary glands and the relationship to current concepts of neoplasia in salivary glands. Oral Surg Oral Med Oral Pathol 69: 53— 67.
- Dardick I., Burford-Mason A. (1994). Pathology of the salivary glands: The contribution of electron microscopy. Micr Res Techn 27: 46—60.[CrossRef]
- The Dutch Act on Animal Experimentation [Stb. 1977] (1991). In: Proefdieren en dierproeven, van Zutphen LFM, Baumans V, Beijnen AC (eds). Academic Press Bunge, Utrecht, pp 337—354.
- Emmiger A., Mohr U. ( 1982). Tumours of the oral cavity, check pouch, salivary glands, oesophagus, stomach and intestines. In: Pathology of Tumours in Laboratory Animals. Tumours of the hamster, Vol 3, Turusov VS (ed). IARC Scientific Publ No 34, Lyon, pp 45—68.
- Glucksmann A., Cherry CP (1973). Tumours ofthe salivary gland. In: Pathology of Tumours in Laboratory Animals. Tumours of the rat, Vol 1, Part 1, Turusov VS (ed). IARC Scientific Publ No 5, Lyon, pp 75—86.
- Gopinath C., Prentice DE, Lewis DJ (1987). The alimentary system and pancreas. In: Experimental Toxicological Pathology, Gopinath C, Prentice DE, Lewis DJ (eds), MTP Press Limited, Lancaster, pp 61—76.
- Greaves P. (2000). Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation, 2nd ed., Elsevier, Amsterdam, pp 321—329.
- Gustafsson H., Carlsoo B., Kjorell U., Thornell L-E. (1986). Immunohistochemical and ultrastructural observations on adenoid cystic carcinoma of salivary glands. Acta Otolaryngol 102: 152—160.[CrossRef][Medline]
[Order article via Infotrieve]
- Heywood R., Wadsworth PF (1981). The experimental toxicology of estrogens. In: Pharmacology of Estrogens. International Encyclopedia of Pharmacology and Therapeutics, Section 106, Chaudhurry RR (ed). Pergamon Press, New York, p 68.
- Hiramatsu M., Kashimata M., Takayama F., Mirami N. (1994). Developmental changes in and hormonal modulation of epidermal growth factor concentration in the rat submandibular gland. J Endocrinol 140(3): 357—363.[Abstract/Free Full Text]
- Hully JR, Benton HP, Alison MR (1984). Isoprenaline-induced cell proliferation in mouse salivary glands: The effect of castration. Virchows Arch B: Zellpathol 47: 95—105.
- Kato K., Yokose S., Tajima Y. (1991). Use of silver enhancement technique for immunohistochemical detection of epidermal growth factor in rat submandibular gland. Biotech Histochem 1: 87—88.[Medline]
[Order article via Infotrieve]
- Long PL ( 1990). Spontaneous neoplastic lesions in the CDF (F-344)/ CrlBR Rat. In: Charles River Laboratories, On-line literature
 http://www.criver.com/techdocs/90febsn/n90tab01.htm . - Miller AS, Hartman GG, Chen S-Y., Edmonds PR, Brightman SA, Harwick RD (1994). Estrogen receptor assay in polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma of salivary gland origin. An immunohistochmical study. Oral Surg Oral Med Oral Pathol 77: 36—40.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Mori M., Hamada K., Naito R., Tsukitani K., Asano K. (1983). Immunohistochemical localization of epidermal growth factor in rodent submandibular glands. Acta Histochem Cytochem 16: 536—547.
- Ormos J., Halasz A. (1991). Electron microscopic study of adenoid cystic carcinoma. Ultrastruct Pathol 15: 149—157.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ozono S., OnozukaM., Sato K., Ito Y. (1991). Immunohistochemical evidence for the presence of progesterone receptor in rat submandibular glands. Cell Struct Funct 16: 511—513.[Web of Science][Medline]
[Order article via Infotrieve]
- Ozono S., Onozuka M., Sato K., Ito Y. (1992). Immunohistochemical localization of estradiol, progesterone, and progesterone receptor in human salivary glands and salivary adenoid cystic carcinomas. Cell Struct Funct 17: 169—175.[Web of Science][Medline]
[Order article via Infotrieve]
- Ozono S., Sato K., Ito Y., Kubota H., Hayashi H., Kato H., Yamamoto T., Watanabe K., Onozuka M. (1995). Immunochemical evidence that tumors elicit the synthesis of estrogen receptors in the submandibular gland of female rats. Experientia 51(3): 220—222.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Pinkstaff CA (1980). The cytology of salivary glands. Int Rev Cytol 63: 141—261.
- Pinkstaff CA (1998). Salivary gland sexual dimorphism: A brief review. Eur J Morphol (suppl.) 36: 31—34.[Web of Science][Medline]
[Order article via Infotrieve]
- Rins de David ML, Caceres A., Goldraij A. (1990). Sexual dimorphism in rat submaxillary gland. Acta Odontol Latinoam 5: 63—69.[Medline]
[Order article via Infotrieve]
- Sakabe K., Seiki K., Fujii-Hanamoto H., Kawashima I. (1988). Progestin and estrogen receptors: Characterization and localization in rat submandibular glands, with special reference to epidermal growth factor. Endocrinol Japan 35(5): 709—723.[Medline]
[Order article via Infotrieve]
- Schuurman H., Krajnc-Franken MAM, Kuper CF, van Loveren H., Vos JG (1991). Immune system. In: Handbook of Toxicologic Pathology, Haschek WM, Rousseaux CG (eds). Academic Press, San Diego, pp 421—483.
- Shick PC, Riordan GP, Foss RD ( 1995). Estrogen and progesterone receptors in salivary gland adenoid cystic carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 80: 440—444.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Tamarin A., Sreebny LM (1965). The rat submaxillary salivary gland, a correlative study by light and electron microscopy. J Morph 117: 295—352.[CrossRef][Medline]
[Order article via Infotrieve]
- Woods AE, Ellis RC (1996). Laboratory Histopathology, A Complete Reference. Churchill Livingstone, New York, p 23.
- Working Group on Animal Health (1994). Recommendations for the Health Monitoring of Mouse, Rat, Hamster, Guineapig and Rabbit Breeding Colonies. Report of the Federation of European Laboratory Animal Science Associations (FELASA) Working Group on Animal Health accepted by the FELASA Board of Management. Lab Anim 28: 1—12.[Medline]
[Order article via Infotrieve]
- Yuan Y. (1991). Female reproductive system. In: Handbook of Toxicologic Pathology, Haschek WM, Rousseaux CG (eds). Academic Press, San Diego, pp 891—931.
Toxicologic Pathology, Vol. 31, No. 1,
1-9 (2003)
DOI: 10.1080/01926230390173798
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