Stable intestinal phenotypic expression of gastric and small intestinal tumor cells induced by N-methyl-N'-nitro-N-nitrosoguanidine or methylnitrosourea in rats.

On the basis of paradoxical concanavalin A (Con A) staining, the tendency of tumor cells of gastric phenotype to shift to intestinal phenotype and the stability of the latter phenotype in stomach tumors of different sizes were examined quantitatively with an image processor. Phenotypic expression of tumors of the small intestine was also studied. One hundred male Wistar rats were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at 50 micrograms/ml in their drinking water for 20 weeks (group 1). Twenty male F344 rats were given methylnitrosourea (MNU) at a dose of 50 mg/kg ip twice a week for 2 weeks (group 2). Rats in group 1 were killed in week 50 of the experiment and rats in group 2 were killed in week 25. In group 1, the percentage areas of intestinal-type cells in small, medium and large adenocarcinoma of the stomach were 0.5, 2.7 and 6.6%, the differences between these values being significant (P less than 0.05-0.01). Intestinal phenotypic expression of tumor cells of the stomach is stable and the proportion of intestinal-type cells in adenocarcinomas of the stomach is higher in the larger tumors. Adenomatous hyperplasias and adenocarcinomas of the small intestine in groups 1 and 2 were all composed entirely of cells of the intestinal type. These results suggested that intestinal-type cells in adenocarcinoma of the stomach did not originate from intestinal metaplasias but from gastric-type cells in stomach adenocarcinomas.