Early changes of glandular stomach in Wistar rats ingesting N-methyl-N'-nitro-N-nitrosoguanidine (MNNG): with special reference to light microscopic, electron microscopic, and enzyme histochemical study of the regenerating epithelium induced by MNNG

Early mucosal changes of the glandular stomach in Wistar rats ingesting N-methyl-N'-nitro-N-nitrosoguanidine were studied. Special attention was paid to clarifying the localization and chronological relationship between the expected regenerative changes and the succeeding carcinoma. For this purpose, drinking water of MNNG at a low concentration was given to the inbred Wistar rats which were sacrificed every second week during the first 35 weeks. In the 5th week, localized erosions appeared, which were constantly observed through about the 20th week. These changes were always located near the midpoint of the lesser curvature. Epithelial cells, which were found there, were studied with light and electron microscope, and with enzyme histochemistry. It has been observed that these cells corresponded with the so-called immature cells in the normal gastric epithelium and also with the regenerating epithelial cells, which were obtained from the vicinity of mechanically induced ulcer of the stomach. From about the 20th week 2 cases showing ectopic gland, 4 adenomatous changes, 2 early carcinomas, and 5 invasive carcinomas were found. All these lesions were located on the lesser curvature, near its midpoint, i.e. exactly the same area where regularly the erosions were observed.