Acute Radiation-Induced Changes in Sprague-Dawley Rat Submandibular Glands: A Histomorphometric Analysis

Abstract

BackgroundRadiation-induced xerostomia is a distressing clinical condition that starts appearing from the initial stages of radiotherapy in head and neck cancer patients. Though submandibular glands contribute to maximum of the “resting salivary” secretions, most of the acute xerostomia experiments so far reported have been on animal parotid glands. Therefore, we assessed and quantified the histologic changes in submandibular glands of Sprague-Dawley (SD) rats using histomorphometry, 24 hours after radiation.MethodsThree SD rats were given single-dose radiation of 15 Gray from a gamma cobalt-60 irradiator. Same number of non-radiated animals was the controls. Animals were sacrificed at 24 hours followed by histopathology and histomorphometry of submandibular glands, where the mean values were analyzed by Student’s t-test.ResultsIrradiated submandibular glands showed highly significant reduction in acinar area (53%: 77.16±5.05% to 36.55±4.90%) and acinar size (87%: 3,447.53 ± 461.03 mm2 to 428.25 ± 75.22 mm2) with concomitant increase in inter-acinar space (3.46 ± 0.67 mm to 10.08 ± 0.60 mm). Acini nuclei displayed anisonucleosis, poikilonucleosis and pyknosis. “Serous acini” had marked morphologic changes, with fluid accumulation between cells, generalized cytoplasmic vacuolation and vascular congestion, while “mucous acini” largely retained cell architecture. Similarly, ductal cells and nuclei also did not show apparent differences. This demonstrated radiosensitivity variations among different submandibular gland cell types.ConclusionEvaluation of acute submandibular acinar cell dysfunctions has helped in quantifying the histologic elements, which mainly contribute to the resting salivary secretions. Findings would aid in future research of radioprotector drugs, salivary glandular regeneration modalities and in devising prudent radiotherapy protocols to address radiation-induced xerostomia.

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

“…Fig. 2 Control submandibular gland shows serous acini (1) , mucous acini (2) , serous demilune (3) , striated duct (4) , blood vessel (5) , (H&E, ×100). H&E, hematoxylin and eosin.…”

“…Stem cell is another cell type in the salivary glands found at both excretory and striated ducts. 5 The stem cells generate progenitor cells that replace the acinar and ductal cells. 4 The life span of acinar and ductal cells in rats is reported to be 60 to 120 days.…”

“…19 Significant histological alterations including cell necrosis, nuclear fragmentation, cell membrane injury, and vacuolation were recorded in the irradiated animal. 5 Atrophy of irradiated salivary gland parenchymal tissue was the end result which replaced by either fibrous or fatty tissue. 20 The irradiated salivary glands showed highly significant reduction in acinar size with increase in inter-acinar space.…”

“…Serous acini are more susceptible to morphological changes while both mucous acini and ductal cells did not show apparent differences. 5,21 Reduction of saliva flow rates and changes in its contents which are associated with loss of parenchymal cells was the end sequala of radiation injuries of salivary glands. 22 A prominent decrease in saliva was seen 7 days after radiotherapy regimen to treat cancers and many cases showed recovery 2 months after complete treatment.…”

Emerging Strategies in Radiation Countermeasure Research

“…Ionizing radiation emanating from all these; major and minor accidents, causes dreadful disease states, death and environmental hazards. Pathways of radiation exposure to humans are from radionuclides deposited on the ground (ground shine), radioactive cloud (cloud shine), inhalation and ingestion through food and water [6][7][8][9]. In short, nuclear reactor accidents cause: "Nuclear war without war".…”