Histogenesis of Rat Colon Carcinoma Induced by N-methyl-N-nitrosourea

Colorectal carcinomas were induced in rats by intrarectal administration of N-methyl-N-nitrosourea (MNU). The process of tumor development, the labeling indices of tumors with 3H-thymidine and the nuclear DNA contents of tumors were examined sequentially. In the early stage, the lesions were small, and usually showed mild to moderate atypia. However, in the larger tumors observed later, the proportions of severely atypical lesions and invasive carcinomas were higher. The labeling indices of tumors also increased with increase in atypism. The distribution patterns of DNA severely atypical intramucosal lesions were similar to, but not identical with, those of invasive carcinomas. The existence of peaks between 2C and 4C indicated the presence of several clonal cell groups. These results showed that most initial lesions induced by MNU administration, which showmd mild to moderate atypia, could be identified as adenomas, but that later the lesions developed into severely atypical lesions and finally into invasive carcinomas; that is, cancers developed by progression.