Development and cell kinetics of colonic tumors induced in mice by dimethylhydrazine

Abstract

Colonic adenomas and carcinomas were induced in mice by intermittent injections of 1,2-dimethylhydrazine for 30 weeks and cell kinetic characteristics of different tumor types were studied by ³H-thymidine autoradiography. Labeling indices of adenomas and several carcinoma types after a single injection of ³H-thymidine were similar, both showing about 20%–23%. There was a tendency for the small adenomas and the poorly differentiated carcinomas to show higher labeling indices than the large adenomas and the well differentiated adenocarcinomas, respectively. By repeated injections of ³H-thymidine, it was shown that all adenoma and carcinoma cells became labeled within 60–70 h after the start of the injections, thereby suggesting a large growth fraction of the DMH-induced adenomas and carcinomas in the mouse colon. No remarkable differences in the labeling patterns were found between the adenomas and carcinomas, on the one hand, and intramucosal carcinomas and invasive carcinomas, on the other. The growth rate of the small adenomas appeared to be greater than that of the large adenomas and the poorly differentiated carcinomas may grow more rapidly than the well differentiated adenocarcinomas. The squamous-cell carcinomas arising in the anal region were shown to grow more rapidly than the adenocarcinomas of the colon. The changing patterns of tumor development were also studied at various times after DMH treatment with special reference to the minute neoplasms and their histogenesis and it was shown that the adenoma cells arising in the crypts accumulate in the upper part of the crypt to form an aberrant proliferative focus from which a neoplasm develops by expansion. The lesions considered to be benign on histological grounds may possibly change into adenocarcinomas of a well differentiated type. The poorly differentiated carcinomas were suggested to arise as de novo malignancy.