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Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland

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Virchows Archiv B

Summary

The submandibular glands of male rats were exposed to 50 Gy X-irradiation as a single dose, with or without pre-treatment with either alpha-adrenergic agonists (noradrenaline, phenylephrine) or a cholinergic antagonist (atropine). The effects were analyzed by morphometric, cytochemical and biophysical methods. When X-irradiated without drug pre-treatment, many serous epithelial cells of the intralobular convoluted ducts displayed morphologic evidence of irreversible radiation damage, in contrast to neighbouring mucous and other cells which were unaffected. The effect was maximal 96 h after irradiation. Serous cells from animals irradiated after pre-treatment with atropine showed much more wide-spread injury than those of animals exposed to X-irradiation only. In contrast, serous cells suffered considerably less damage if their secretory granules had been depleted 1 or 2 h before irradiation with either noradrenaline or phenylephrine. Other epithelial cells showed no modulation of their slight radioresponsiveness by these drugs. The observations were substantiated by morphometry of three cell types: (a) mucous cells, (b) non-granulated serous and intralobular striated duct cells, and (c) granulated serous cells. The findings suggest that the striking radiosensitivity of salivary gland serous epithelial cells is linked to their content of secretory granules. These granules are rich in heavy metals, as demonstrated cytochemically with the sulphide silver method (SSM). Using particle-induced X-ray emission (PIXE) spectroscopy, the principal metals were shown to be Zn, Mn and Fe. It is conceivable that membranes which enclose organelles rich in metals with the ability to form redox systems (e.g. Fe2+ ai Fe3+) show enhanced sensitity to radiation damage due to the metal-catalyzed induction of lipid peroxidation by ionizing radiation. Disruption of secretory granules would be expected to release lytic enzymes into the cell sap, resulting in autolysis. This hypothesis is supported by the findings that atropine-which increases the number of granulated serous cells-enhances radiosensitivity, while noradrenaline and phenylephrine-which cause degranulation of serous cells-decrease radiosensitivity.

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References

  • Abok K, Blomquist E, Ericsson J, Brunk U (1983) Macrophage radiosensitivity in culture as a function of exposure to ionic iron. Virchows Arch [Cell Pathol] 42:119–129

    CAS  Google Scholar 

  • Alno A (1961) Regeneration capacity of the submandibular gland in rat and mouse. Acta Pathol Microbiol Scand [suppl] 149:1–84

    Google Scholar 

  • Alper T (1977) The role of membrane damage in radiation-induced cell death. Adv Exp Med Biol 84:139–165

    PubMed  CAS  Google Scholar 

  • Arnold WH, Orstavik TB, Hoick M (1983) A 4-methoxy-2-naphthylamide substrate for the histochemical localization of esteroproteases in the submandibular gland of the rat. Histo-chemical J 15:139–146

    Article  CAS  Google Scholar 

  • Aust SD, Svingen BA (1982) The role of iron in enzymatic lipid peroxidation. In: Pryor WA (eds) Free radicals in biology. Academic Press, New York, pp 1–28

    Google Scholar 

  • Berdjis CC (1961) Irradiation as a cause of “masculinization” in submandibular glands. Br J Exptl Pathol 42:38–42

    CAS  Google Scholar 

  • Berdjis CC (1962) Cortisone and radiation. Strahlentherapie 119:545–556

    Google Scholar 

  • Bergonie J, Speder E (1911) Sur quelques formes de reactions precoces apres des irradiations Röntgen. Arch Elect Med 19:241–245

    Google Scholar 

  • Berkman MD, Kronman JH (1970) A histochemical study of the effects of castration and testosterone administration on the major salivary glands of Swiss mice. Acta Anat 76:200–219

    PubMed  CAS  Google Scholar 

  • Blozis GG, Robinson JE (1968) Oral tissue changes caused by radiation therapy and their management. Dent Clin N Am 12:643–657

    Google Scholar 

  • Brun A, Brunk U (1970) Histochemical indications for lysosomal localization of heavy metals in normal rat brain and liver. J Histochem Cytochem 18:820–827

    PubMed  CAS  Google Scholar 

  • Brunk U, Brun A (1972) Histochemical evidence for lysosomal uptake of lead in tissue cultured fibroblasts. Histochemie 29:140–146

    Article  PubMed  CAS  Google Scholar 

  • Burstone MS (1953) A histochemical study of normal and irradiated salivary gland tissue in the mouse. Anat Record 115:543–547

    Article  CAS  Google Scholar 

  • Carl W, Schaaf NG, Chen TY (1972) Oral care of patients irradiated for cancer of the head and neck. Cancer 30:448–453

    Article  PubMed  CAS  Google Scholar 

  • Chakrabarti SG, Hanks CT, Johnson SP (1975) Biochemical and morphological studies of rat submandibular gland: II. Partial purification of proteins from granule-rich fraction. J Dent Res 54:948–959

    PubMed  CAS  Google Scholar 

  • Cherry CP, Glucksmann A (1959) Injury and repair following irradiation of salivary glands in male rats. Br J Radiol 32:596–608

    PubMed  CAS  Google Scholar 

  • Chomette G, Auriol M, Vaillant JM, Bertrand JCh, Chenal Ch (1981) Effects of irradiation on the submandibular gland of rat. An enzyme histochemical and ultrastructural study. Virchows Arch [Pathol Anat] 391:291–299

    Article  CAS  Google Scholar 

  • Conger AD (1973) Loss and recovery of taste acuity in patients irradiated to the oral cavity. Rad Res 53:338–347

    Article  CAS  Google Scholar 

  • Cutler LS, Chaudhry AP (1975) Cytodifferentiation of striated duct cells and secretory cells of the convoluted granular tubules of the rat submandibular gland. Am J Anat 143:201–218

    Article  PubMed  CAS  Google Scholar 

  • Daly TE, Drane JB, MacComb WS (1972) Management of problems of the teeth and jaw in patients undergoing irradiation. Am J Surg 124:539–542

    Article  PubMed  CAS  Google Scholar 

  • del Regato JA (1939) Dental lesions observed after roentgen therapy in cancer of the buccal cavity, pharynx and larynx. Am J Roent 42:404–410

    Google Scholar 

  • Desai ID, Sawant PL, Tappel L (1964) Peroxidative and radiation damage to isolated lysosomes. Biochim Biophys Acta 86:277–285

    PubMed  CAS  Google Scholar 

  • El-mofty SK, Kahn AJ (1981) Early membrane injury in lethally irradiated salivary gland cells. Int J Radiat Biol 39:55–62

    Article  CAS  Google Scholar 

  • Eneroth CM, Henrikson CO, Jakobson PA (1972) Effect of fractionated radiotherapy on salivary gland function. Cancer 30:1147–1153

    Article  PubMed  CAS  Google Scholar 

  • Flon H, Gerstner R, Mitchell OG, Feldman A (1970) Salivary glands of heteromyid rodents, with a summary of the literature on rodent submandibular gland morphology. J Morphol 131:179–194

    Article  PubMed  CAS  Google Scholar 

  • Frank RM, Herdly J, Philippe E (1965) Acquired dental defects and salivary gland lesions after irradiation for carcinoma. J Am Dent Assoc 70:868–883

    PubMed  CAS  Google Scholar 

  • Goldberg J, Martini LE, Batchelor A (1960) Biochemical changes in the tissues of animals with iron, acid phosphatase and other enzymes. Biochem J 77:252–262

    Google Scholar 

  • Goldfischer S (1965) The localization of copper in the pericanalicular granules (lysosomes) of liver in Wilson’s disease (hepatolenticular degeneration). Am J Pathol 46:977–983

    PubMed  CAS  Google Scholar 

  • Grünberg H (1964) Histological and karyometric changes in human major and minor salivary glands after exposure to ionizing radiation with cobalt 60. Arch Ohren Nasen Kehlkopfheilk 184:235–248

    Article  Google Scholar 

  • Harris JW (1970) Effects of ionizing radiation on lysosomes and other intracellular membranes. Adv Biol Med Phys 13:273–387

    PubMed  CAS  Google Scholar 

  • Ito M (1967) Biological effects of X-irradiation on salivary glands of mice. Rad Res 30:283–300

    Article  CAS  Google Scholar 

  • Junqueira LC, Fajer A, Rabinovitch M, Frankenthal L (1949) Biochemical and histochemical observation on the sexual dimorphism of mice submandibular glands. J Cell Comp Physiol 34:129–159

    Article  CAS  Google Scholar 

  • Junqueira LCU, Toledo AMS, Saad A (1962) Studies on the physiology of rat and mouse submaxillary gland. 1. Amylase and protease activity in serum, submaxillary gland, and submaxillary saliva of rat and mouse. In: Sreebny LM, Meyer J (eds) Salivary glands and their secretions: Proc Int Conf, University of Washington, Seattle, Washington, pp 105–128

    Google Scholar 

  • Kashima HK, Kirkham WR, Andrews JR (1965) Post-irradiation sialadenitis: a study of the clinical features, histopathologic changes and serum enzyme variations following irradiation of human salivary glands. Am J Roentgenol Rad Ther Nucl Med 94:271–291

    Google Scholar 

  • Kahre S, Jayakumar A, Trivedi A, Kesavan PC, Prasad R (1982) Radiation effects on membranes. I. Cellular permeability and cell survival. Rad Res 90:233–243

    Article  Google Scholar 

  • Kiortsis M (1968) Combined lethal effect of zink chloride and gamma irradiation on Bacillus megaterium. Nature [Lond] 217:746–747

    Article  CAS  Google Scholar 

  • Kohn HI, Kallman RF, Berdjis CC, De Dome KB (1957) Late effects of whole-body X-irradiation in the mouse. Some gross and histologic aspects of the development of morbidity prior to the terminal state, with special reference to the gonad, uterus, heart, liver, kidney, and submaxillary gland. Rad Res 7:407–435

    Article  CAS  Google Scholar 

  • Lacassagne A (1940) Dimorphisme sexuel de la glande sous-maxillaire chez la souris. CR Soc Biol [Paris] 133:180–181

    CAS  Google Scholar 

  • Leeson CR (1967) Structure of salivary glands. In: Code CF (ed) Handbook of physiology. Alimentary Canal, vol II, Chap 32, Washington DC. Am Physiol Soc, pp 463–495

    Google Scholar 

  • Lindh U (1982) Elemental mapping of tissue sections at cellular resolution: a nuclear microprobe investigation. Nucl Instrum Meth 197:185–190

    Article  CAS  Google Scholar 

  • Lindquist RR (1968) Studies on the pathogenesis of hepatolenticular degeneration. II. The effect of copper on rat liver lysosomes. Am J Pathol 53:903–927

    PubMed  CAS  Google Scholar 

  • Minato A, Hirose S, Hayashi S (1967) Studies on proteases in submaxillary gland. I. Fractionation and general characteristics of rat submaxillary proteases. Chem Pharm Bull 15:1356–1361

    PubMed  CAS  Google Scholar 

  • Mira JG, Wescott WB, Starcke EN, Shannon IL (1981) Some factors influencing salivary function when treating with radiotherapy. Int J Rad Oncol Biol Phys 7:535–541

    CAS  Google Scholar 

  • Mossman KL (1982) Quantitative radiation dose-response relationships for normal tissues in man. I. Gustatory tissue response during photon and neutron radiotherapy. Rad Res 91:265–274

    Article  CAS  Google Scholar 

  • Novi AM, Baserga R (1971) Association of hypertrophy and DNA synthesis in mouse salivary glands after chronic administration of isoproterenol. Am J Pathol 62:295–102

    PubMed  CAS  Google Scholar 

  • Phillips MR (1970) X-ray-induced changes in function and structure of the rat parotid gland. J Oral Surg 28:432–437

    PubMed  CAS  Google Scholar 

  • Raynaud J, Rebeyrotte MP (1949) Difference d’activite amylasique de la glande sous-maxillaire des souris mäles et des souris femelles; conditionement de cette activite par les hormones androgenes. CR Acad Sci 229:2045–2047

    Google Scholar 

  • Rubin P, Casarett GW (1968) In: Saunders WB Co. Clinical radiation pathology. Philadelphia, pp 241–292

    Google Scholar 

  • Riekkinen PJ, Niemi M (1968) Androgen-dependent salivary gland protease in the rat. Endocrinology 83: 1224–1231

    PubMed  CAS  Google Scholar 

  • Santangelo MV, Toto PD (1965) Radiation effects on submandibular gland. J Dent Res 44:1291–1298

    Google Scholar 

  • Shafer WG, Muhler JC (1953) Effect of gonadectomy and sex hormones on the structure of the rat salivary glands. J Den Res 32:262–268

    CAS  Google Scholar 

  • Shafer WG (1953) The effect of single and fractionated doses of selectively applied X-ray irradiation on the histologic structure of the major salivary glands of the rat. J Dent Res 32:796–806

    PubMed  CAS  Google Scholar 

  • Shannon IL, McCrary BR, Starcke EN (1977) A saliva substitute for use by xerostomic patients undergoing radiotherapy to the head and neck. Oral Surg 44:656–661

    Article  PubMed  CAS  Google Scholar 

  • Shear M (1972) Substrate film techniques for the histochemical demonstration of amylase and protease in salivary glands. J Dent Res [suppl] 51:368–380

    CAS  Google Scholar 

  • Sholley MM, Sodicoff M, Pratt NE (1974) Early radiation injury in the rat parotid gland. Reaction of acinar cells and vascular endothelium. Lab Invest 31:340–354

    PubMed  CAS  Google Scholar 

  • Silverman S Jr. Chierici G (1965) Radiation therapy of oral carcinoma. 1. Effects on oral tissues and management of the periodontium. J Periodont 36:478–484

    PubMed  Google Scholar 

  • Sinn DP, Stoker NG, Epker BN (1972) Effects of fractionated doses of cobalt 60 irradiation on rabbit submandibular glands: light microscopic studies. J Oral Surg 30:277–283

    PubMed  CAS  Google Scholar 

  • Sodicoff M, Conger AD, Pratt NE (1979) Isoproterenol in comparison to WR-2721 as a chemoradioprotector of the rat parotid gland. Invest Radiol 14:166–170

    Article  PubMed  CAS  Google Scholar 

  • Sreebny LM (1960) Study of salivary gland proteases. Ann NY Acad Sci 85:182–188

    Article  PubMed  CAS  Google Scholar 

  • Stern MH, Turner JE, Jett LS, Mincer H, McGinnis JP (1976) Electron microscopic changes in rat parotid and submandibular glands subsequent to total body irradiation with fast neutrons. Oral Surg 42:620–630

    Article  PubMed  CAS  Google Scholar 

  • Tappel AL (1973) Lipid peroxidation damage to cell components. Fed Proc 32:1870–1874

    PubMed  CAS  Google Scholar 

  • van den Brenk HAS, Hurley RA, Gomez C, Richter W (1969) Serum amylase as a measure of salivary gland radiation damage: hyperamylasaemia following fractionated exposure to 4 MV X-rays delivered in high pressure oxygen, and effects of certain steroids on this response. Br J Radiol 42:688–700

    PubMed  Google Scholar 

  • Verity MA, Brown WJ (1970) Hg2+-induced kidney necrosis. Subcellular localization and structure-linked lysosomal enzyme changes. Am J Pathol 61:57–74

    PubMed  CAS  Google Scholar 

  • Watkins DK (1970) Effect of oxygen on the release of enzymes from lysosomes after irradiation. Br J Radiol 43:152–153

    Article  PubMed  CAS  Google Scholar 

  • Wescott WB, Starcke EN, Shannon IL (1975) Chemical protection against postirradiation dental caries. Oral Surg 40:709–719

    Article  PubMed  CAS  Google Scholar 

  • Wills ED, Wilkinson AE (1966) Release of enzymes from lysosomes by irradiation and the relation of lipid peroxidation formation to enzyme release. Biochem J 99:657–666

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology II, Linköping University, S-58185, Linköping

    Kisia Abok & Ulf Brunk

  2. Department of Pathology, Uppsala University, S-75185, Uppsala, Sweden

    Kisia Abok & Jan Ericsson

  3. Department of Oncology and Radiophysics, Uppsala University, S-75185, Uppsala, Sweden

    Bo Jung

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  1. Kisia Abok
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  2. Ulf Brunk
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Abok, K., Brunk, U., Jung, B. et al. Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland. Virchows Archiv B Cell Pathol 45, 443–460 (1984). https://doi.org/10.1007/BF02889885

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  • DOI: https://doi.org/10.1007/BF02889885

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