2, 3, 7, 8-tetrachlorodibenzo-p-dioxin induces apoptosis in the dorsal midbrain of zebrafish embryos by activation of arylhydrocarbon receptor

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 re presentative toxicities of halogenated aromatic hydrocarbons. In the presen t study, the effects of TCDD on cell death in zebrafish embryos (Danio reri o) during the early stage of development were investigated. As shown by ter minal transferase-mediated nick-end-labeling staining, TCDD exposure signif icantly increased the occurrence of pycnotic cell death (PCD), especially i n the dorsal midbrain (optic tectum). The ultrastructures of these pycnotic cells showed apoptotic features such as condensation and cleavage of chrom atin. TCDD-induced PCD was mimicked by beta-naphthoflavone (AhR agonist), a nd inhibited by alpha-naphthoflavone (AhR antagonist). These results sugges t that AhR activation can induce apoptosis in the central nervous system du ring development. (C) 2001 Elsevier Science Ireland Ltd. All rights reserve d.