Shinozuka J, Suzuki M, Noguchi N, Sugimoto T, Uetsuka K, Nakayama H, Doi K
Department of Veterinary Pathology, Faculty of Agriculture, University of Tokyo, Japan.
Toxicol Pathol. 1998 Sep-Oct;26(5):674-81. doi: 10.1177/019262339802600512.
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.
我们在雌性ICR:CD-1小鼠经口接种10 mg/kg体重的T-2毒素后长达48小时，检查了骨髓和脾红髓中T-2毒素诱导的损伤。组织病理学上，骨髓和脾红髓显示出明显的细胞减少。在骨髓中，由于未成熟粒细胞、成红细胞和淋巴细胞的减少，髓细胞数量显著下降。其余显示核固缩或核碎裂的细胞的细胞核通过TdT介导的dUTP缺口末端标记（TUNEL）法呈阳性染色，并且这些TUNEL阳性细胞显示出凋亡的超微结构特征。通过琼脂糖凝胶电泳，在骨髓样本中清晰检测到DNA梯带。脾红髓中TUNEL阳性细胞的数量比脾白髓中增加得更早。因此，T-2毒素诱导的造血组织和淋巴组织损伤是由组成细胞的凋亡引起的。我们认为造血微环境的损伤可能在骨髓细胞凋亡的诱导中也起间接作用。
