[Histopathologic study of rapidly induced colonic carcinoma in rats by N-methyl-N-nitrosourea--with special reference...

The rat model of N-methyl-N-nitrosourea (MNU)-induced colorectal carcinogenesis was studied to determine histogenesis and evaluate early proliferative lesions and invasive carcinoma by the measurement of DNA content. Twenty-five male Fischer rats, weighing 150-160 g, were intra-rectally given MNU dissolved in distilled water, at a dose of 2 mg/rat, 3 times weekly for 5 weeks. Histopathologically, the lesions were classified into 3 foci, that is dysplastic focus composed of single gland, intra-mucosal dysplastic focus and macroscopic or invasive carcinoma. Macroscopic lesions were gradually increased in number and size with time. The earliest lesion, which could be recognized as single gland dysplastic foci, not only preceded the occurrence of invasive carcinoma, but also appeared most frequently in the colonic segment that subsequently showed the site of the highest incidence of advanced carcinoma. Thus, single gland foci might be precancerous lesions. However, on the basis of similar findings of the DNA distribution pattern in single gland foci, intramucosal foci and invasive carcinoma, these foci could be regarded as "de novo carcinoma" or, at least, it can be said that the development of carcinoma was not preceded by adenomatous polyp in our present experiment.