Study of kinetics of epithelial cell populations in normal tissues of the rat's intestines and in carcinogenesis

Cell proliferation in adenocarcinomas induced in the rat's colon by parenteral injection of 1,2-dimethylhydrazine was compared with that in normal colonic epithelium by means of autoradiographs. The distinct zone of proliferation, typical of the intestines, was not observed in the tumours, and cells replicated nearly in all segments of neoplasms. Tumour enterocytes were found to have a longer short mitotic cycle (16 instead of 11 hrs), due, chiefly, to an extension of G₁-period duration. They were also characterized by a more pronounced heterogeneity as far as the values of t_s and t_G2 are concerned, and, probably, by the formation of an R₂-population. Both the index of S-phase (29 %) and labelled cell fraction (87 %) after 6 injections of ³H-thymidine spaced at six-hour intervals, were lower in adenocarcinomas than in the zone of maximum proliferation in the descending colon (45 and 100 %, respectively) and yet higher than the same parameters calculated for the whole population of the intestinal epithelium (17 and 60%, respectively). As far as proliferation parameters go, adenocarcinoma cells highly resemble those of the crypt bottom population in control animals, which was found to consist of several subpopulations with a varying mean duration of the mitotic cycle, and where stem enterocytes are likely to occur. When enterocytes become malignant, disturbances in their differentiation decrease cell shedding into the intestinal lumen and, thus, cause tumours to arise and develop.