Summary
Radioimmunoassays and immunocytochemical techniques were used to assess the effect of cyclocytidine, an antitumor agent, on the level and localization of Epidermal Growth Factor (EGF) in the submandibular gland of the male mouse. A single intraperitoneal injection of 150 mg/kg of cyclocytidine caused, within 6 h, a degranulation of the granular convoluted tubule (GCT) cells and reduced the concentration of immunoreactive EGF in gland extracts by more than 90 %. This effect was largely abolished by the administration of dibenzyline but not by propranolol, indicating that the secretory effect of the drug on the GCT cells is mediated by α-adrenergic receptors. By immunocytochemical staining EGF was localized to the GCT cells. Immunocytochemical staining revealed the same trends in changes in EGF concentration as the radioimmunoassays. However, even at the peak of the cyclocytidine effect there were cells which retained their secretory granules and apparently their EGF complement. In addition, there was a lobular variation in the secretory response. Cyclocytidine caused a transient increase in the blood level of EGF. Furthermore, it stimulated amylase secretion from the gland, which also involved α-adrenergic receptors. Cyclocytidine will be useful in future analyses of the release of various biologically active substances from the GCT cells of the mouse submandibular gland.
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We thank Mrs. T. Ross for her assistance in the morphologic studies. The cyclocytidine was obtained through the courtesy of Dr. H.B. Wood, Jr., Drug Development Branch of the Division of Cancer Treatment, NCI, NIH and Dr. J. Holland, Mount Sinai School of Medicine
This investigation was supported by United States Public Health Service Research Grants CA 17038 and CA 11155 from The National Cancer Institute
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Barka, T., Gresik, E.W. & van der Noen, H. Stimulation of secretion of epidermal growth factor and amylase by cyclocytidine. Cell Tissue Res. 186, 269–278 (1978). https://doi.org/10.1007/BF00225536
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DOI: https://doi.org/10.1007/BF00225536