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. 1986 Sep;124(3):469–478.

Acute and late radiation injury in rhesus monkey parotid glands. Evidence of interphase cell death.

L C Stephens, G K King, L J Peters, K K Ang, T E Schultheiss, J H Jardine
PMCID: PMC1888342  PMID: 3766705

Abstract

Acute and chronic salivary gland dysfunction are common sequelae of radiotherapy for head and neck cancer; but the associated morphologic changes, especially of the acute damage, have received relatively little study. For investigation of the morphologic characteristics of acute radiation injury to parotid glands, rhesus monkeys were studied 1-72 hours after parotid irradiation with single doses of 2.5-15.0 Gy. The acute damage from all doses was clearly expressed by 24 hours. Histologically, parotid glands irradiated with 2.5 or 5.0 Gy had random degeneration and necrosis of the serous acinar cells. Doses of 7.5-15.0 Gy produced widespread degeneration along with necrosis of whole acini. Serous cell damage was accompanied by neutrophilic inflammation that subsided after 24 hours to become replaced by plasma cell and lymphocytic infiltrates. Parotid glands receiving 7.5-15.0 Gy were atrophic at 16-22 weeks after irradiation and showed no recovery by 40 weeks. Although parotid acinar cells are well-differentiated nondividing cells, these observations show that they express lethal radiation injury in interphase within hours of receiving a radiation dose as low as 2.5 Gy. This is unlike most mammalian cells that express radiation injury during mitosis. Chronic atrophy is a consequence of this direct, irreversible, and early injury, rather than the result of radiation-induced changes in the vasculature.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abok K., Brunk U., Jung B., Ericsson J. Morphologic and histochemical studies on the differing radiosensitivity of ductular and acinar cells of the rat submandibular gland. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;45(4):443–460. doi: 10.1007/BF02889885. [DOI] [PubMed] [Google Scholar]
  2. BURSTONE M. S. A histochemical study of normal and irradiated salivary gland tissue in the mouse. Anat Rec. 1953 Mar;115(3):543–557. doi: 10.1002/ar.1091150307. [DOI] [PubMed] [Google Scholar]
  3. Beumer J., 3rd, Silverman S., Jr, Benak S. B., Jr Hard and soft tissue necroses following radiation therapy for oral cancer. J Prosthet Dent. 1972 Jun;27(6):640–644. doi: 10.1016/0022-3913(72)90311-3. [DOI] [PubMed] [Google Scholar]
  4. Bloomer W. D., Hellman S. Normal tissue responses to radiation therapy. N Engl J Med. 1975 Jul 10;293(2):80–83. doi: 10.1056/NEJM197507102930206. [DOI] [PubMed] [Google Scholar]
  5. Bowers D. E., Jr, Connors N. A., Cannon M. S. Irradiated salivary glands in the rhesus monkey. A light microscopic study. J Med Primatol. 1981;10(4-5):228–239. doi: 10.1159/000460080. [DOI] [PubMed] [Google Scholar]
  6. Brown L. R., Dreizen S., Handler S., Johnston D. A. Effect of radiation-induced xerostomia on human oral microflora. J Dent Res. 1975 Jul-Aug;54(4):740–750. doi: 10.1177/00220345750540040801. [DOI] [PubMed] [Google Scholar]
  7. CHERRY C. P., GLUCKSMANN A. Injury and repair following irradiation of salivary glands in male rats. Br J Radiol. 1959 Sep;32:596–608. doi: 10.1259/0007-1285-32-381-596. [DOI] [PubMed] [Google Scholar]
  8. Chencharick J. D., Mossman K. L. Nutritional consequences of the radiotherapy of head and neck cancer. Cancer. 1983 Mar 1;51(5):811–815. doi: 10.1002/1097-0142(19830301)51:5<811::aid-cncr2820510511>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  9. Cheng V. S., Downs J., Herbert D., Aramany M. The function of the parotid gland following radiation therapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 1981 Feb;7(2):253–258. doi: 10.1016/0360-3016(81)90444-2. [DOI] [PubMed] [Google Scholar]
  10. Dreizen S., Brown L. R., Handler S., Levy B. M. Radiation-induced xerostomia in cancer patients. Effect on salivary and serum electrolytes. Cancer. 1976 Jul;38(1):273–278. doi: 10.1002/1097-0142(197607)38:1<273::aid-cncr2820380141>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  11. Dreizen S., Daly T. E., Drane J. B., Brown L. R. Oral complications of cancer radiotherapy. Postgrad Med. 1977 Feb;61(2):85–92. doi: 10.1080/00325481.1977.11712115. [DOI] [PubMed] [Google Scholar]
  12. ENGLISH J. A. Morphologic effects on irradiation on the salivary glands of rats. J Dent Res. 1955 Feb;34(1):4–11. doi: 10.1177/00220345550340011301. [DOI] [PubMed] [Google Scholar]
  13. El-Mofty S. K., Kahn A. J. Early membrane injury in lethally irradiated salivary gland cells. Int J Radiat Biol Relat Stud Phys Chem Med. 1981 Jan;39(1):55–62. doi: 10.1080/09553008114550071. [DOI] [PubMed] [Google Scholar]
  14. Elzay R. P., Levitt S. H., Sweeney W. T. Histologic effect of fractionated doses of selectively applied megavoltage irradiation on the major salivary glands of the albino rat. Radiology. 1969 Jul;93(1):146–152. doi: 10.1148/23.1.146. [DOI] [PubMed] [Google Scholar]
  15. Eneroth C. M., Henrikson C. O., Jakobsson P. A. Effect of fractionated radiotherapy on salivary gland function. Cancer. 1972 Nov;30(5):1147–1153. doi: 10.1002/1097-0142(197211)30:5<1147::aid-cncr2820300502>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  16. FRANK R. M., HERDLY J., PHILIPPE E. ACQUIRED DENTAL DEFECTS AND SALIVARY GLAND LESIONS AFTER IRRADIATION FOR CARCINOMA. J Am Dent Assoc. 1965 Apr;70:868–883. doi: 10.14219/jada.archive.1965.0220. [DOI] [PubMed] [Google Scholar]
  17. GREENSPAN J. S., MELAMED M. R., PEARSE A. G. EARLY HISTOCHEMICAL CHANGES IN IRRADIATED SALIVARY GLANDS AND LYMPH-NODES OF THE RAT. J Pathol Bacteriol. 1964 Oct;88:439–453. doi: 10.1002/path.1700880207. [DOI] [PubMed] [Google Scholar]
  18. Harwood T. R., Staley C. J., Yokoo H. Histopathology of irradiated and obstructed submandibular salivary glands. Arch Pathol. 1973 Sep;96(3):189–191. [PubMed] [Google Scholar]
  19. KOHN H. I., KALLMAN R. F., BERDJIS C. C., DE OME K. B. 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. Radiat Res. 1957 Oct;7(4):407–435. [PubMed] [Google Scholar]
  20. Marks J. E., Davis C. C., Gottsman V. L., Purdy J. E., Lee F. The effects of radiation of parotid salivary function. Int J Radiat Oncol Biol Phys. 1981 Aug;7(8):1013–1019. doi: 10.1016/0360-3016(81)90152-8. [DOI] [PubMed] [Google Scholar]
  21. Michalowski A. Effects of radiation on normal tissues: hypothetical mechanisms and limitations of in situ assays of clonogenicity. Radiat Environ Biophys. 1981;19(3):157–172. doi: 10.1007/BF01324183. [DOI] [PubMed] [Google Scholar]
  22. Mira J. G., Wescott W. B., Starcke E. N., Shannon I. L. Some factors influencing salivary function when treating with radiotherapy. Int J Radiat Oncol Biol Phys. 1981 Apr;7(4):535–541. doi: 10.1016/0360-3016(81)90140-1. [DOI] [PubMed] [Google Scholar]
  23. Mossman K. L., Henkin R. I. Radiation-induced changes in taste acuity in cancer patients. Int J Radiat Oncol Biol Phys. 1978 Jul-Aug;4(7-8):663–670. doi: 10.1016/0360-3016(78)90190-6. [DOI] [PubMed] [Google Scholar]
  24. Mossman K. L. Quantitative radiation dose-response relationships for normal tissues in man. II. Response of the salivary glands during radiotherapy. Radiat Res. 1983 Aug;95(2):392–398. [PubMed] [Google Scholar]
  25. Mossman K. L., Scheer A. C. Complications of radiotherapy of head and neck cancer. Ear Nose Throat J. 1977 Mar;56(3):145–149. [PubMed] [Google Scholar]
  26. Mossman K. L., Shatzman A. R., Chencharick J. D. Effects of radiotherapy on human parotid saliva. Radiat Res. 1981 Nov;88(2):403–412. [PubMed] [Google Scholar]
  27. Mossman K., Shatzman A., Chencharick J. Long-term effects of radiotherapy on taste and salivary function in man. Int J Radiat Oncol Biol Phys. 1982 Jun;8(6):991–997. doi: 10.1016/0360-3016(82)90166-3. [DOI] [PubMed] [Google Scholar]
  28. Narayan K., Cliff W. J. Morphology of irradiated microvasculature: a combined in vivo and electron-microscopic study. Am J Pathol. 1982 Jan;106(1):47–62. [PMC free article] [PubMed] [Google Scholar]
  29. Pratt N. E., Sodicoff M. Ultrastructural injury following x-irradiation of rat parotid gland acinar cells. Arch Oral Biol. 1972 Aug;17(8):1177–1186. doi: 10.1016/0003-9969(72)90088-x. [DOI] [PubMed] [Google Scholar]
  30. SHACKLEFORD J. M., KLAPPER E. C. Structure and carbohydrate histochemistry of mammalian salivary glands. Am J Anat. 1962 Jul;111:25–47. doi: 10.1002/aja.1001110104. [DOI] [PubMed] [Google Scholar]
  31. Searle J., Kerr J. F., Bishop C. J. Necrosis and apoptosis: distinct modes of cell death with fundamentally different significance. Pathol Annu. 1982;17(Pt 2):229–259. [PubMed] [Google Scholar]
  32. Shackleford J. M., Wilborn W. H. Structural and histochemical diversity in mammalian salivary glands. Ala J Med Sci. 1968 Apr;5(2):180–203. [PubMed] [Google Scholar]
  33. Shannon I. L., Trodahl J. N., Starcke E. N. Radiosensitivity of the human parotid gland. Proc Soc Exp Biol Med. 1978 Jan;157(1):50–53. doi: 10.3181/00379727-157-39988. [DOI] [PubMed] [Google Scholar]
  34. Sholley M. M., Sodicoff M., Pratt N. E. Early radiation injury in the rat parotid gland. Reaction of acinar cells and vascular endothelium. Lab Invest. 1974 Oct;31(4):340–354. [PubMed] [Google Scholar]
  35. Stephens L. C., King G. K., Ang K. K., Schultheiss T. E., Peters L. J. Surgical and microscopic anatomy of parotid and submandibular salivary glands of rhesus monkeys (Macaca mulatta). J Med Primatol. 1986;15(2):105–119. [PubMed] [Google Scholar]
  36. Stephens L. C., King G. K., Peters L. J., Ang K. K., Schultheiss T. E., Jardine J. H. Unique radiosensitivity of serous cells in rhesus monkey submandibular glands. Am J Pathol. 1986 Sep;124(3):479–487. [PMC free article] [PubMed] [Google Scholar]
  37. Van den Brenk H. A., Hurley R. A., Gomez C., Richter W. 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. 1969 Sep;42(501):688–700. doi: 10.1259/0007-1285-42-501-688. [DOI] [PubMed] [Google Scholar]
  38. Wescott W. B., Mira J. G., Starcke E. N., Shannon I. L., Thornby J. I. Alterations in whole saliva flow rate induced by fractionated radiotherapy. AJR Am J Roentgenol. 1978 Jan;130(1):145–149. doi: 10.2214/ajr.130.1.145. [DOI] [PubMed] [Google Scholar]
  39. van den Brenk H. A., Sparrow N., Moore V. Effect of x-radiation on salivary gland growth in the rat. I. Effect of single doses on post-natal differentiation and growth of acinar and duct components. Int J Radiat Biol Relat Stud Phys Chem Med. 1969;16(3):241–266. doi: 10.1080/09553006914551261. [DOI] [PubMed] [Google Scholar]

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