Inducement of canine gastric cancer by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG).

Abstract

Achievements in the experimental inducement of canine gastric cancer in Japan are reviewed. Canine gastric cancer was initially induced experimentally by the administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water. However, intestinal sarcoma caused death before the gastric cancer was detected. By giving an N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)-soaked diet to dogs, we specifically induced gastric cancer and followed the process of carcinogenesis by X-ray, endoscopy, and biopsy. The initial macroscopic findings were areas of discoloration, with erosion or mucosal unevenness which became visible from approximately the 9th to 10th experimental months in mongrel dogs and around the 13th to 17th months in beagle dogs. The protruded type of cancer occurred in mongrel dogs early in the experimental period, while the less protruded but more ulcerated gastric cancer occurred in beagle dogs later. Histological examination of the autopsied stomachs 277, 395, 546 and 813 day in mongreal dogs and 804, 946, and 1591 day in beagle dogs revealed well differentiated, poorly differentiated, and undifferentiated adenocarcinoma. In animals with a lengthy survival (more than 600 days from the start of the experiment), metastases to lymph nodes, and, rarely, to liver, lung, bones, and other organs, were observed, as well as peritonitis carcinomatosa. Heterotransplantation of gastric cancer to nude mice succeeded to the fifth passage. Development of scirrhous cancer was induced in dogs by the combined use of ENNG and subcutaneous injection of gastrin, indicating that the experimentally induced canine gastric cancer resembled human gastric cancer. Although the induction of canine gastric cancer takes 2-3 years and the macroscopic type and time period differs among individual dogs, our results in the experimental induction of canine gastric cancer should be useful in various areas of research that require an animal model, such as genetic alteration during carcinogenesis, modulation of carcinogenesis, and prevention of gastric cancer.