Early changes in the dynamics of crypt cell populations in mouse colon following administration of...

The effects of the carcinogen, 1,2-dimethylhydrazine (DMH), on the proliferative characteristics of the crypt cell population of mouse colon were studied. DMH (20 mg/kg body weight) was injected s.c., weekly, for 2, 8, 16, 20, or 26 weeks. At the end of each treatment period, a group of animals was injected with [3H]thymidine and killed. After 2 weeks of DMH treatment, the crypts appeared normal histologically, but the total number of cells, the number of labeled cells, and the percentage of labeled cells per crypt column had increased. The relative distribution of labeled cells in crypt columns was not changed. DMH treatment did not affect the phases of the cell cycle of epithelial cells and the transit time of these cells through the crypt. None of the indices of crypt dynamics were altered further with the appearance of focal atypias (after 16 weeks of DMH). However, the total number of cells per crypt increased and the percentage of labeled cells decreased as adenocarcinomas developed in adjacent areas of the mucosa (after 20 to 26 weeks of DMH). The exact role of these early mucosal changes in the eventual development of malignant tumor has not been established. However, it appears that DMH carcinogenesis may involve two steps; (a) an initial increase in the number of mitotocally active cells leading to an enlarged cell population; and (b) an eventual transformation of at least some of the crypt cells of the enlarged population.