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 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.
Dong
W
W
Department of Toxicology, School of Veterinary Medicine, Gakuen University, Rakuno, Japan.
Teraoka
H
H
Kondo
S
S
Hiraga
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001571:Benzoflavones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000002:abnormalities* / Q000187:drug effects / Q000473:pathology; D004791:Enzyme Inhibitors / Q000633:toxicity; D005260:Female; D020287:In Situ Nick-End Labeling; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013477:Superior Colliculi / Q000002:abnormalities* / Q000187:drug effects / Q000473:pathology; D013723:Teratogens / Q000633:toxicity*; D015027:Zebrafish / Q000002:abnormalities* / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000633:toxicity
D001571:Benzoflavones; D004791:Enzyme Inhibitors; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; C011512:alpha-naphthoflavone; D019324:beta-Naphthoflavone