Fossmark R, Martinsen T C, Bakkelund K E, Kawase S, Torp S H, Waldum H L
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim.
Scand J Gastroenterol. 2004 Oct;39(10):919-26. doi: 10.1080/00365520410003281.
Among inbred female cotton rats (Sigmodon hispidus) 25%-50% of the animals develop spontaneous gastric carcinomas, whereas males have an incidence of less than 1%. The carcinomas are enterochromaffin-like (ECL)-cell derived. Animals with gastric carcinomas also have hypergastrinaemia and gastric hypoacidity, but the mechanism behind the hypoacidity is unknown. Carcinomas have been found in all female cotton rats with spontaneous hypergastrinaemia lasting more than 4 months, and a gastrin receptor antagonist prevents the development of carcinoma. The purpose of the present study was to investigate whether induced hypergastrinaemia in male cotton rats would also result in carcinomas.
Hypergastrinaemia was induced by partial corpectomy of male cotton rats, aiming at removal of 80%-90% of the corpus. A control group was sham-operated.
All partially corpectomized animals developed persistent hypergastrinaemia. Six months after the operation, 9 out of 13 partially corpectomized animals developed gastric cancer. In the dysplastic mucosa surrounding the tumours there was an increase in chromogranin A immunoreactive cells, where numerous cells also were stained using the Sevier-Munger technique. Tumour tissue also contained cells that were chromogranin A positive and stained by Sevier-Munger.
ECL-cell carcinomas can be induced in male cotton rats by partial corpectomy. This supports a previous statement that spontaneous carcinomas in female cotton rats are caused by gastric hypoacidity and hypergastrinaemia. In hypergastrinaemic animals, ECL-cell carcinomas develop independently of gender within a relatively short period of time, and cotton rats therefore represent an interesting model for studying gastric carcinogenesis.
在近交系雌性棉鼠（棉鼠属）中，25% - 50%的动物会自发发生胃癌，而雄性的发病率低于1%。这些癌起源于肠嗜铬样（ECL）细胞。患有胃癌的动物也有高胃泌素血症和胃酸过少，但胃酸过少背后的机制尚不清楚。在所有自发高胃泌素血症持续超过4个月的雌性棉鼠中都发现了癌，并且一种胃泌素受体拮抗剂可预防癌的发生。本研究的目的是调查雄性棉鼠中诱导的高胃泌素血症是否也会导致癌症。
通过对雄性棉鼠进行部分体部切除术诱导高胃泌素血症，目标是切除80% - 90%的体部。对照组进行假手术。
所有接受部分体部切除术的动物都出现了持续性高胃泌素血症。术后6个月，13只接受部分体部切除术的动物中有9只发生了胃癌。在肿瘤周围发育异常的黏膜中，嗜铬粒蛋白A免疫反应性细胞增加，其中许多细胞也用Sevier - Munger技术染色。肿瘤组织中也含有嗜铬粒蛋白A阳性且被Sevier - Munger染色的细胞。
通过部分体部切除术可在雄性棉鼠中诱导ECL细胞癌。这支持了先前的一种说法，即雌性棉鼠中的自发癌是由胃酸过少和高胃泌素血症引起的。在高胃泌素血症的动物中，ECL细胞癌在相对较短的时间内不依赖性别发生，因此棉鼠是研究胃癌发生的一个有趣模型。
