A B S T R A C T Investigations have outlined pancreatic secretory and synthetic responses to gastrointestinal hormones. However, there is little information concerning hormonal influences on pancreatic growth.These studies were designed to examine effects of chronic administration of bethanechol and cholecystokinin-pancreozymin (CCK-PZ) on the pancreas. M\Iale albino rats were given saline, bethanechol, 6 mg/kg, or CCK-PZ, 20 U/kg, intraperitoneally twice daily and killed after 5 days. DNA was determined by the diphenylamine method using calf thymus DNA as a standard (20). RNA was determined by the orcinol method using ribose as a standard (21). Protein was determined by the biuret method using bovine serum albumin as the standard (22). Radioactivity was assayed in a Packard liquid scintillation counter (Packard Instrument Co., Inc., Downers Grove, Ill.) using a phosphor developed by Patterson and Greene (23). Fig. 1 shows rates of incorporation of ["C]thymidine into pancreatic DNA. Under these conditions of in vitro incubation, incorporation was near linear for 30, 60, 90, 120, and 150 min. Other investigators, using different tissues, have shown that thymidine nucleotide pools were small and that there was rapid equilibration between intracellular and extracellular thymidine pools (24). In addition, at concentrations of ["C]thymidine used in these experiments, no labeled ["C]thymidine triphosphate remained unincorporated in the cell (25). These observations were considered sufficient to validate the use of in vitro incubation of pancreas for short-term studies of DNA synthesis. A 90 min period of in vitro incubation was used for other experiments. RESULTS

We induced pancreatic adenocarcinomas in Long-Evans rats by placing crystals, 2-3 mg, of 7,12-dimethylbenz[a]anthracene (DMBA) in a 2- to 3-mm incision in the "head" of the pancreas approximately 1 cm from the duodenum. The incisions were closed with one or two silk sutures. The animals were killed 4-10 months after DMBA implantation, and nodules were removed and routinely prepared for light and/or electron microscopic study. Histologic organization varied from normal, through areas of tubule-like structures, to sheets of pleomorphic tumor cells. Electron microscopic study of tumor cells revealed large electron-lucent nuclei that frequently had irregular outlines and prominent nucleoli. The predominant feature of the cytoplasm was abundant rough endoplasmic reticulum. Zymogen granules were rare. Adjacent cells sometimes were jointed by an apical junctional complex to form a lumen into which projected irregular microvilli. A basal lamina sometimes occurred at the bases of the tumor cells. The fine structural similarity of these tumor cells to acinar cells was noted.

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