Dong W, Teraoka H, Kondo S, Hiraga T
Department of Toxicology, School of Veterinary Medicine, Gakuen University, Rakuno, Japan.
Neurosci Lett. 2001 May 11;303(3):169-72. doi: 10.1016/s0304-3940(01)01743-8.
Neurotoxic effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) has not been fully elucidated, despite the known potent agonist of arylhydrocarbon receptor (AhR), which activation induces cytochrome P450 1A and several representative toxicities of halogenated aromatic hydrocarbons. In the present study, the effects of TCDD on cell death in zebrafish embryos (Danio rerio) during the early stage of development were investigated. As shown by terminal transferase-mediated nick-end-labeling staining, TCDD exposure significantly increased the occurrence of pycnotic cell death (PCD), especially in the dorsal midbrain (optic tectum). The ultrastructures of these pycnotic cells showed apoptotic features such as condensation and cleavage of chromatin. TCDD-induced PCD was mimicked by beta-naphthoflavone (AhR agonist), and inhibited by alpha-naphthoflavone (AhR antagonist). These results suggest that AhR activation can induce apoptosis in the central nervous system during development.
尽管已知2,3,7,8-四氯二苯并对二恶英（TCDD）是芳烃受体（AhR）的强效激动剂，其激活可诱导细胞色素P450 1A以及卤代芳烃的几种典型毒性，但TCDD的神经毒性作用尚未完全阐明。在本研究中，研究了TCDD对斑马鱼胚胎（Danio rerio）发育早期细胞死亡的影响。如末端脱氧核苷酸转移酶介导的缺口末端标记染色所示，TCDD暴露显著增加了固缩性细胞死亡（PCD）的发生率，尤其是在背侧中脑（视顶盖）。这些固缩细胞的超微结构显示出凋亡特征，如染色质凝聚和裂解。β-萘黄酮（AhR激动剂）可模拟TCDD诱导的PCD，而α-萘黄酮（AhR拮抗剂）可抑制该过程。这些结果表明，AhR激活可在发育过程中诱导中枢神经系统凋亡。
