T-2 toxin-induced apoptosis in hematopoietic tissues of mice.

We examined T-2 toxin-induced lesions in the bone marrow and splenic red pulp as many as 48 hr after oral inoculation with 10 mg/kg body weight of T-2 toxin in female ICR:CD-1 mice. Histopathologically, the bone marrow and splenic red pulp showed a significant hypocellularity. In the bone marrow, the number of myelocytes significantly decreased due to the loss of immature granulocytes, erythroblasts, and lymphocytes. The nuclei of the remaining cells showing pyknosis or karyorrhexis were positively stained by the TdT-mediated dUTP nick end labeling (TUNEL) method, and these TUNEL-positive cells showed ultrastructural characteristics of apoptosis. With agarose gel electrophoresis, DNA ladders were clearly detected in bone marrow samples. The number of TUNEL-positive cells in splenic red pulp increased earlier than it did in the splenic white pulp. Thus, T-2 toxin induced-lesions in the hematopoietic tissues and in the lymphoid tissues were brought about by apoptosis of component cells. We believe that damage to the hematopoietic microenvironment may also play an indirect role in the induction of apoptosis in the bone marrow.