title: Embryotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): the embryonic vasculature is a physiological target for TCDD-induced DNA damage and apoptotic cell death in Medaka (Orizias latipes).
abstract: Vertebrate embryos are extremely sensitive to environmental contaminants known as planar halogenated hydrocarbons (PHHs). The physiological targets that mediate PHH-induced embryotoxicity are not known. We have characterized embryotoxicity in medaka (Orizias latipes) caused by 2,3,7,8-tetrachlorodibezo-p-dioxin (TCDD), the prototypic PHH. DNA degradation in cells of the embryonic vasculature and loss of functional integrity of the medial yolk vein were demonstrated in TCDD-exposed embryos. Pharmacological intervention with piperonyl butoxide inhibited TCDD-induced DNA degradation, restored the functional integrity of the medial yolk vein, and protected against the embryotoxicity of TCDD. Treatment of TCDD-exposed embryos with the antioxidant N-acetylcysteine also provided significant protection against the embryotoxicity of TCDD. These results demonstrate that DNA damage and consequent cell death in the embryonic vasculature are key physiological mediators of TCDD-induced embryotoxicity.
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia 65212, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Cantrell
authors.forename: L H
authors.initials: LH
authors.lastname: Lutz
authors.forename: D E
authors.initials: DE
authors.lastname: Tillitt
authors.forename: M
authors.initials: M
authors.lastname: Hannink
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004586:Electrophoresis; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000196:embryology; D009420:Nervous System / Q000187:drug effects / Q000196:embryology; D009990:Oryzias; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*
chemical_list: D000072317:Polychlorinated Dibenzodioxins