Hypergastrinemia induced by partial corpectomy results in ECL-cell carcinoma in male cotton rats

Abstract

Approximately 50 percent of females and one percent of males in a strain of Japanese cotton rats (Stgmodon hispidns) develop spontaneous enterochromaffm-like(ECL)-ceU derived gastric carcinomas and have hypergastrinemia secondary to gastric hypo/anacithty. The mechanism behind the hypo/anacidity is unknown. We have found carcinomas in all female cotton rats with spontaneous hypergastrinemia lasting more than four months. These animals represent an excellent model for studying ECL-cell carcinogenesis. The development of these tumors is prevented by a gastrin antagonist as well as by a somatostatin analogue. We have therefore previously argued that the carcinogenesis is due to hypergastrinemia. Whether induced hypergastrinemia would result in ECL-cell carcinomas cotton rats has not been examined. We therefore performed partial corpectomy, an operation that has resulted in persistent hypergastrinemia and ECDcell derived tumors in Sprague-Dowley rats more than two years postoperatively. Male cotton rats were chosen as they have the lowest incidence of spontaneous carcinomas. Male cotton rats were operated b)' ~n ia l corpectomy aiming at removal of 90% of the corpus. A control group was sham-operated. All animals were given B 12-injections monthly. Serum gastrin was measured every second month. At termination the stomach was examined histologically (haematoxylin and eosin) and immunohistochemically with an antibody against chromogranin A, a neuroendocrine cell marker. All partially corpectomized animals developed persistent hypergastrinemia and ECL-cell derived cancer after six months. Immunohistochemieal examination confirmed a neuroendocrine origin of the tumors. This study demonstrates that ECL-ceU carcinomas can be induced in male cotton rats in six months. The results support our previous statement that spontaneous tumors developing in cotton rats are caused by gastric hypoacidity and hypergastrinemia. Given persistent hypergastrinemia, ECL--cell carcinomas will develop in cotton rats independent of sex within a relatively short period of time.