The effect of 5-fluorouracil on the mitotic cycle and DNA synthesis in the epithelium of mouse small intestine.
The examinations were performed on 42 mice of the Porton strain. The experimental animals were injected intraperitoneally with the dose of 75 mg of 5-fluorouracil per kg body weight. The first experimental group received injections of [3H]thymidine within 48 hours and the second group within 96 hours of the injection of 5-fluorouracil. Two mice from each group were killed at within 1, 2, 4, 8, 12, 24, and 48 hours of the [3H]thymidine injection. Calculations of the mitotic index and time of duration of individual phases of the mitotic cycle in epithelial cells of the small intestine were based on application of the autoradiographic method. These studies lead to the conclusion that 5-fluorouracil disturbs the course of metabolic processes in the cell, which are also related with the distribution of the genetic material. Histological examinations show that 5-fluorouracil produces profound morphological changes in the intestine, which affect both the intestinal epithelium and the connective tissue stroma. The autoradiographic tests revealed a considerable suppression of the mitotic activity of the epithelium of intestinal crypts. Moreover, it was shown that 5-fluorouracil inhibits the mitotic activity of the intestinal epithelium by diminishing the number of cells capable of entering into mitosis. Nevertheless, by 96 hours following introduction of a single dose of 5-fluorouracil normal morphological structure and mitotic activity of the intestinal wall cells are restored.