T-2 TOXIN-INDUCED APOPTOSIS IN HEMATOPOIETIC TISSUES OF MICE

We examined T-2 toxin-induced lesions in the bone marrow and splenic r ed pulp as many as 48 hr after oral inoculation with 10 mg/kg body wei ght of T-2 toxin in female ICR:CD-1 mice. Histopathologically, the bon e 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 we re positively stained by the TdT-mediated dUTP nick end labeling (TUNE L) method, and these TUNEL-positive cells showed ultrastructural chara cteristics of apoptosis. With agarose gel electrophoresis, DNA ladders were clearly detected in bone marrow samples. The number of TUNEL-pos itive cells in splenic red pulp increased earlier than it did in the s plenic white pulp. Thus, T-2 toxin induced-lesions in the hematopoieti c tissues and in the lymphoid tissues were brought about by apoptosis of component cells. We believe that damage to the hematopoietic microe nvironment may also play an indirect role in the induction of apoptosi s in the bone marrow.