Altered Cyclic Adenosine 3: 5'Monophosphate Metabolism and Enzymatic Profiles of a Transplantable Murine Submaxillary Gland Carcinoma (Myoepithelioma)

The cyclic nucleotide system has been characterized in a transplantable murine submaxillary gland carcinoma. Thymidine incorporation into tumor cell DNA during log phase growth was 10-fold greater than in normal submaxillary gland and was not affected by isoproterenol (IPR). Injection of IPR Increased thymidine incorporation into submaxillary gland DNA 6-fold. Tumor adenylate cyclase activity was depressed relative to submaxillary gland and was not stimulated by IPR. Submaxillary gland adenylate cyclase activity was increased 3-fold in response to 10-4 MIPR. The tumor high-Km cytosol cyclic adenosine 3‘:5’phosphate and cyclic guanosine 3‘:5’phosphate phosphodiesterase activities were elevated 2-and 9-fold, respectively, over submaxillary gland. Consequently, endogenous cyclic adenosine 3‘:5’phosphate levels in the tumor were about one-third the level found in normal salivary glands. Normal submaxillary gland secretory products (amylase and epidermal and nerve growth factors) were all reduced in tumor preparations. The carcinoma can thus be characterized as a rapidly dividing, malignant tumor with decreased levels of submaxillary gland secretory products and a loss in the ability to respond to β-adrenergic stimulation.