| PCB126 exposure disrupts zebrafish ventricular and branchial but not early neural crest development. | |
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MedLine Citation:
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PMID: 18660518 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have used zebrafish and 3,3',4,4',5-pentachlorobiphenyl (PCB126) to investigate the developmental toxicity of polychlorinated biphenyls (PCBs) that exert their effects through the aryl hydrocarbon receptor (AHR). We found that cardiac and neural crest (NC)-derived jaw and branchial cartilages are specifically targeted early in development. The suite of malformations, which ultimately leads to circulatory failure, includes a severely dysmorphic heart with a reduced bulbus arteriosus and abnormal atrioventricular and outflow valve formation. Early NC migration and patterning of the jaw and branchial cartilages was normal. However, the jaw and branchial cartilages failed to grow to normal size. In the heart, the ventricular myocardium showed a reduction in cell number and size. The heart and jaw/branchial phenotype could be rescued by pifithrin-alpha, a blocker of p53. However, the function of pifithrin-alpha in this model may act as a competitive inhibitor of PCB at the AHR and is likely independent of p53. Morpholinos against p53 did not rescue the phenotype, nor were zebrafish with a mutant p53-null allele resistant to PCB126 toxicity. Morpholino knockdown of cardiac troponin T, which blocks the onset of cardiac function, prevented the PCB126-induced cardiac dysmorphogenesis but not the jaw/branchial phenotype. The cardiovascular characteristics appear to be similar to hypoplastic left heart syndrome (HLHS) and introduce the potential of zebrafish as a model to study this environmentally induced cardiovascular malformation. HLHS is a severe congenital cardiovascular malformation that has previously been linked to industrial releases of dioxins and PCBs. |
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Authors:
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Adrian C Grimes; Kyle N Erwin; Harriett A Stadt; Ginger L Hunter; Holly A Gefroh; Huai-Jen Tsai; Margaret L Kirby |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-07-26 |
Journal Detail:
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Title: Toxicological sciences : an official journal of the Society of Toxicology Volume: 106 ISSN: 1096-0929 ISO Abbreviation: Toxicol. Sci. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-10-09 Completed Date: 2008-12-23 Revised Date: 2010-09-21 |
Medline Journal Info:
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Nlm Unique ID: 9805461 Medline TA: Toxicol Sci Country: United States |
Other Details:
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Languages: eng Pagination: 193-205 Citation Subset: IM |
Affiliation:
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Department of Molecular and Cellular Biology and Pathobiology, Medical University of South Carolina, Charleston, South Carolina 29425, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple
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chemically induced*,
embryology,
metabolism,
prevention & control Animals Animals, Genetically Modified Benzothiazoles / pharmacology Body Patterning / drug effects Branchial Region / drug effects*, metabolism Cell Death Cell Differentiation Cell Movement Cell Proliferation / drug effects Environmental Pollutants / toxicity* Heart Defects, Congenital / chemically induced*, embryology, metabolism, prevention & control Heart Ventricles / drug effects*, embryology, metabolism Jaw Abnormalities / chemically induced Morpholines / metabolism Neural Crest / drug effects* Oligonucleotides / metabolism Phenotype Polychlorinated Biphenyls / toxicity* Time Factors Toluene / analogs & derivatives, pharmacology Troponin T / genetics, metabolism Tumor Suppressor Protein p53 / genetics, metabolism Zebrafish / embryology*, genetics, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 70140//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Benzothiazoles; 0/Environmental Pollutants; 0/Morpholines; 0/Oligonucleotides; 0/Polychlorinated Biphenyls; 0/Troponin T; 0/Tumor Suppressor Protein p53; 0/pifithrin; 108-88-3/Toluene; 57465-28-8/3,4,5,3',4'-pentachlorobiphenyl |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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