Development of tumors in the glandular stomach of rats after oral administration of carcinogens. I. Histological findings.

Experimental carcinomas in the glandular stomach of rats were induced by oral administration of MNNG (M-methyl-N'-nitro-N-nitrosoguanidin) for 35 weeks or ENNG (N-ethyl-N'-nitro-N-nitrosoguanidin) for 20 weeks. Rats were killed at different times after beginning of carcinogen treatment and tissue specimens were prepared for histologic investigation. Particular interest was placed on the development of tumors and on pathological findings possibly contributing to early diagnosis of stomach cancer. During the development of tumors, several dysplastic reactions were observed in the antral mucosa. They could be classified into 4 groups: One was regenerative hyperplasia (1) that meant irregular glandular proliferations without cell atypism at the margin of erosions and ulcers. This lesion was mainly found 1-9 weeks after administration of MNNG. In glandular hyperplasia (2) either crypts or glands were extended and mucosal layers were thickened. No signs of cell atypism were observed. This lesion was mainly found 12-17 weeks after administration of MNNG. Dysplasia (3) was combined with considerable structural modifications and cellular atypism. However, this lesion was limited to the mucosal layer. Neoplastic changes (4) were characterized by marked cellular atypism and extension to tunica submucosa and tunica serosa. Some tumors showed the histological patterns of benign tumors, but most of them were adenocarcinomas. In some cases metastases into pancreas, liver and lymph nodes and in one case into the 12th rib were observed. No particular enzyme patterns were found by histochemistry.