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

Neurosci Lett. 2001 May 11;303(3):169-72. doi: 10.1016/s0304-3940(01)01743-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Benzoflavones / pharmacology
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian / abnormalities*
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / pathology
  • Enzyme Inhibitors / toxicity
  • Female
  • In Situ Nick-End Labeling
  • Male
  • Microscopy, Electron
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / ultrastructure
  • Polychlorinated Dibenzodioxins / toxicity*
  • Receptors, Aryl Hydrocarbon / agonists
  • Receptors, Aryl Hydrocarbon / antagonists & inhibitors
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Superior Colliculi / abnormalities*
  • Superior Colliculi / drug effects
  • Superior Colliculi / pathology
  • Teratogens / toxicity*
  • Zebrafish / abnormalities*
  • Zebrafish / metabolism
  • beta-Naphthoflavone / toxicity

Substances

  • Benzoflavones
  • Enzyme Inhibitors
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Teratogens
  • alpha-naphthoflavone
  • beta-Naphthoflavone