Gastric carcinoma was induced in inbred Wistar rats by p.o. administration of N-methyl-N′-nitro-N-nitrosoguanidine for 25 weeks, and cell proliferation and growth of the gastric carcinoma in an incipient stage were studied. A microscopic cancer was found by 24 weeks, and macroscopic cancers were found after 27 weeks. All the cancers were a single lesion located at the midpoint of the lesser curvature of the stomach. Histologically, they were tubular adenocarcinomas. The mucosal changes predisposing to the development of carcinomas were focal erosions and dysplasias confined to the midpoint of the lesser curvature. The malignant transformation appeared to occur in the dysplastic cells of the eroded mucosa by 17 to 18 weeks after N-methyl-N′-nitro-N-nitrosoguanidine treatment. Following the malignant change, the labeling indices of the tissues with [3H]thymidine decreased, suggesting an elongation of cell cycle time. By repeated injections of [3H]thymidine, a time required for all the cancer cells to enter S phase (reflecting the maximum cell cycle time) was estimated to be about 3.5 days. This gave a theoretical doubling time for the gastric cancers. On the other hand, from the temporal observations of tumor volumes, it was shown that the gastric cancers in an incipient stage underwent exponential growth with a doubling time of 14 days. The difference between the theoretical and actual doubling time might reflect a cell loss rate in the cancer tissue.


Supported by a grant-in-aid for cancer research from the Ministry of Education, Science and Culture, Japan, and by Grant He 537/5 from Deutsche Forschungsgemeinschaft.

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