Stimulation of secretion of epidermal growth factor and amylase of cyclocytidine

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 tubules (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 alpha-adrenergic receptors. By 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 transiet increase in the blood level of EGF. Furthermore, it stimulated amylase secretion from the gland, which also involved alpha-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.