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Investigating the Toxicity of Oxygenated Polycyclic Aromatic Hydrocarbons (OPAHs) in Developing Zebrafish Public Deposited

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  • The toxicity of a group of oxygenated polycyclic aromatic hydrocarbons (OPAHs) was investigated using embryonic zebrafish. An immediate goal was to determine the relative toxicity of these compounds and to explore the toxicity mechanisms. It is thought that some OPAHs cause toxicity by binding and activating the aryl hydrocarbon receptor (AHR), a well conserved vertebrate signaling pathway. Ligand binding to this receptor can induce the expression of specific genes and subsequent proteins such as CYP1A. Immunohistochemistry was used to determine whether the CYP1A protein expression was induced in zebrafish following exposure to five structurally diverse OPAHs: benz[a]anthracene-7,12-dione (BADO), 1,9-benz-10-anthrone (BAO), 9,10-phenanthrenequinone (PQO), 9,10-anthraquinone, and xanthone. PQO did not induce CYP1A expression yet exposure caused 100% mortality over 2uM, suggesting AHR –independent toxicity mechanisms. BAO exposure caused significant malformations above 5uM, but also failed to increase the expression of the CYP1A protein. BADO induced CYP1A throughout the vascular system, and exposures produced numerous malformations. Using a functional null AHR2 fish line, we demonstrated that the CYP1A expression in fish exposed to BADO is AHR2-dependent. Anthraquinone and xanthone both induced CYP1A expression, but unlike BADO, the expression was restricted to the liver. Our results demonstrate that OPAH toxicity and AHR activation are structurally dependent. These results pave the way for future comparative studies aimed at assessing the risk that OPAHs pose to humans and other vertebrates.
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  • Howard Hughes Medical Institute
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  • description.provenance : Made available in DSpace on 2012-05-25T18:00:07Z (GMT). No. of bitstreams: 3HHMI-AnnikaSwanson_2011.pptx: 17308323 bytes, checksum: 595af44af36dd331f841e7daedd60fff (MD5)license_rdf: 21091 bytes, checksum: 6b700a38fb61133bb71e5cac54dd59be (MD5)license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)
  • description.provenance : Approved for entry into archive by Sue Kunda(sue.kunda@oregonstate.edu) on 2012-05-25T18:00:07Z (GMT) No. of bitstreams: 3HHMI-AnnikaSwanson_2011.pptx: 17308323 bytes, checksum: 595af44af36dd331f841e7daedd60fff (MD5)license_rdf: 21091 bytes, checksum: 6b700a38fb61133bb71e5cac54dd59be (MD5)license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)
  • description.provenance : Submitted by Annika Swanson (swansoan@onid.orst.edu) on 2012-05-25T16:14:32ZNo. of bitstreams: 3HHMI-AnnikaSwanson_2011.pptx: 17308323 bytes, checksum: 595af44af36dd331f841e7daedd60fff (MD5)license_rdf: 21091 bytes, checksum: 6b700a38fb61133bb71e5cac54dd59be (MD5)license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)

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