Effects of 1,2-dimethylhydrazine on the number of epithelial cells present in the villi, crypts, and mitotic pool along the rat small intestine.

Young adult male rats received 1,2-dimethylhydrazine (25 mg/kg) twice weekly for 2 months and once a week thereafter for up to 6 months. Histological samples of duodenum, jejunum, and upper, mid-, and terminal ileum were prepared from groups killed at each month. Using cell counts, the average number of epithelial cells was determined per representative section of villi and crypts and was used as an index of villus size and crypt size, respectively. The average number of mitotic figures in representative crypt sections was also determined. All three parameters increased during treatment, and the increments showed a specific pattern in relation to time and intestinal region. Mitotic number showed a consistent change all along the small intestine: close to 20% rise by 3 months; decrease to near control level by the fourth month; and a rise thereafter. Probably, a systemic stimulation of mitotic activity by 1,2-dimethylhydrazine took place. The crypt size index changed similarly, showing highly significant correlation with mitotic number. This correlation indicated that average mitotic time and cell cycle time remained unchanged and the number of divisions increased in progenitor cells. Calculations showed that only a fraction of the progenitor cells was involved. These were probably “initiated” cells. There was a net increase of initiated cell numbers with time, but a sharp drop at 4 months indicated that there is a mechanism inducing a regression of the initiated cell population. Villus size increased linearly in the duodenum and jejunum. In the ileum, there was also a net increase but with some initial fluctuation. In general, villus size seemed to increase so as to maintain a fairly stable tumover time. This would mean that the increased mitotic activity was balanced by increasing differentiation.