De Waal E J, Rademakers L H, Schuurman H J, Van Loveren H, Vos J G
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Arch Toxicol. 1993;67(8):558-64. doi: 10.1007/BF01969269.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known for inducing cortical atrophy in the rat thymus. The present study was conducted to provide ultrastructural evidence for the cortical epithelium to be a target for TCDD in vivo. Juvenile male Wistar rats were orally intubated once with either 50 or 150 micrograms/kg TCDD and killed 4 or 10 days thereafter. Major changes were found in the cortical thymic epithelium. First, a relative shift occurred from "pale" to darker cortical epithelial cell types, as judged by their nuclear and cytoplasmic electron density. This effect was most prominent at 10 days after exposure to 150 micrograms/kg TCDD. The increased electron density of the cortical epithelium indicates an altered state of cellular differentiation. Secondly, at the 150 micrograms/kg dose level focal epithelial cell aggregates were seen both at day 4 and day 10 after administration. This aggregation may either be compound induced or represent a secondary event to the collapse of the thymic stroma. Thirdly, increased vacuolation of cortical epithelial cells was apparent. This effect is interpreted as a consequence rather than a cause of thymocyte depletion from the cortex. This study indicates that TCDD exposure affects the cortical epithelium of the rat thymus at a high dose level. Electron microscopy reveals that the differentiation of epithelial cells is altered. In addition, epithelial cell aggregates are formed.
2,3,7,8-四氯二苯并-对-二噁英(TCDD)以诱导大鼠胸腺皮质萎缩而闻名。本研究旨在提供超微结构证据,证明皮质上皮是TCDD在体内的作用靶点。将幼年雄性Wistar大鼠一次性经口灌胃给予50或150微克/千克的TCDD,然后在4或10天后处死。在胸腺皮质上皮中发现了主要变化。首先,根据核和细胞质电子密度判断,皮质上皮细胞类型从“浅色”向深色发生了相对转变。这种效应在暴露于150微克/千克TCDD后10天最为明显。皮质上皮细胞电子密度增加表明细胞分化状态发生了改变。其次,在150微克/千克剂量水平,给药后第4天和第10天均可见局灶性上皮细胞聚集。这种聚集可能是化合物诱导的,也可能是胸腺基质塌陷的继发事件。第三,皮质上皮细胞空泡化增加明显。这种效应被解释为皮质中胸腺细胞耗竭的结果而非原因。本研究表明,高剂量水平的TCDD暴露会影响大鼠胸腺的皮质上皮。电子显微镜显示上皮细胞的分化发生了改变。此外,还形成了上皮细胞聚集。