Induction of gastric adenocarcinoma in rats by N-methyl-N-nitro-N-nitroso-guanidine and ultrastructural changes of epithelial cells of the pyloric gland region.

Rats of non-pure strain were allowed to drink N-Methyl-N-Nitro-N-Nitroso-guanidine (MNNG) solution (200-250 micrograms per milliliter) ad libitum. After 14 months, in addition to MNNG, each of them was fed with 1 ml of saturated NaCl solution once a week. During a period of 18 months, there were 5 cases of gastric adenocarcinoma and 2 cases of adenocarcinoma of the duodenum among 18 experimental rats. Besides, there were a few cases of papilloma of the fore-stomach and carcinoma of the lung. In 17 control rats, no tumors of the gastro-intestinal tract were seen. Microscopic examination of the mucosa of the pyloric gland region of the stomach in the experimental rats showed that the deep epithelial cells of the gastric pit exhibited a marked degree of proliferation and a malignant change had started in these cells. Electron microscopic observation of these epithelial cells revealed that the the proliferating cells showed only increased nucleocytoplasmic ratio, while those with atypical hyperplasia showed that the form of the nucleus and the changes in the basement membrane and intercellular junctions were somewhat similar to those of malignant cells. It is believed that increase in concentration of the carcinogens and prolongation of the time of contact with them may induce malignant tumors in the insensitive animal.