Apoptosis and cell proliferation of small intestinal villi in mitomycin C-treated rats

Mitomycin C (MMC) therapy often causes toxicity affecting the small intestine. We investigated the relationship between pathological manifestations and cell death, or the proliferation of small intestinal villi in rats treated with MMC. The length of the villi, apoptosis, and cell proliferation were evaluated in the small intestine at 3, 7, and 11 days after MMC treatment by the TUNEL method, BrdU-immunohistochemistry, and transmission electron microscopy. In MMC-treated rats, the body weight decreased until day 7 and recovered from day 8, while most rats had watery stools from days 4 to 7. The villi were the shortest on day 7 and were still shorter on day 11 than in the control group. The highest incidence of TUNEL-positive cells in the small intestinal crypts was observed on day 3, and the number decreased thereafter to reach the control level on day 11. The percentage of BrdU-labeled cells was the highest on day 3 and the lowest on day 7, but recovered to the control level on day 11. The clinical symptoms caused by MMC treatment are consistent with the changes of villous length that reflect the viability of stem cells in the small intestinal crypts about 4 days earlier.