T-2 toxin-induced apoptosis in intestinal crypt epithelial cells of mice

The characteristics of T-2 toxin-induced cell damage in the intestinal crypt epithelia was investigated in mice. Following T-2 toxin-inoculation (0, 2.5, 5 and 10 mg/kg b.w.), dead cells showing pyknosis were sporadically observed in the crypt epithelia, and the nuclei of these cells were strongly stained by the modified TUNEL method which detects fragmented DNA in situ. Electron microscopically, the dead cells were characterized by shrinkage of the cell body and condensation of nuclear chromatin frequently along the nuclear membrane, and such nuclei were sometimes fragmented into small pieces. These morphological characteristics are well consistent with those of apoptosis. The mitotic index in the crypt epithelia drastically decreased at 6 hours after T-2 toxin-inoculation (6 HAI), but thereafter it recovered to almost the same value with that in control mice at 48 HAI. On the other hand, the apoptotic index in the crypt epithelia increased with the lapse of time. Clear mouse strain- and sex-differences were detected in the apoptotic index but not in the mitotic index. This is the first report that T-2 toxin caused apoptotic cell death in the intestinal crypt epithelial cells.