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Full-Text Articles in Medicine and Health Sciences

Fluoranthene, But Not Benzo[A]Pyrene, Interacts With Hypoxia Resulting In Pericardial Effusion And Lordosis In Developing Zebrafish, Cole W. Matson, Alicia R. Timme-Laragy, Richard T. Di Giulio Nov 2008

Fluoranthene, But Not Benzo[A]Pyrene, Interacts With Hypoxia Resulting In Pericardial Effusion And Lordosis In Developing Zebrafish, Cole W. Matson, Alicia R. Timme-Laragy, Richard T. Di Giulio

Alicia R. Timme-Laragy

Previous research has documented several PAHs that interact synergistically, causing severe teratogenicity in developing fish embryos. The coexposure of CYP1A inhibitors (e.g. FL or ANF) with AHR agonists (e.g. BaP or BNF) results in a synergistic increase in toxicity. As with chemical CYP1A inhibitors, it has also been shown that CYP1A morpholinos exacerbate BNF-induced embryotoxicity. We hypothesized that a hypoxia-induced reduction in CYP1A activity in BNF or BaP-exposed zebrafish embryos would similarly enhance pericardial effusion and other developmental abnormalities. BaP, BNF, ANF, and FL exposures, both individually and as BaP+FL or BNF+ANF combinations, were performed under hypoxia and normoxia. CYP1A …


Cyp1b1 Knockdown Does Not Alter Synergistic Developmental Toxicity Of Polycyclic Aromatic Hydrocarbons In Zebrafish (Danio Rerio), Alicia Timme-Laragy, Pamela Noyes, Donald Buhler, Richard Di Giulio Jun 2008

Cyp1b1 Knockdown Does Not Alter Synergistic Developmental Toxicity Of Polycyclic Aromatic Hydrocarbons In Zebrafish (Danio Rerio), Alicia Timme-Laragy, Pamela Noyes, Donald Buhler, Richard Di Giulio

Alicia R. Timme-Laragy

Polycyclic aromatic hydrocarbons (PAHs) are contaminants increasing in the environment largely due to burning of fossil fuels. Our previous work identified a synergistic toxicity interaction in zebrafish embryos occurring when PAHs that are agonists for the aryl hydrocarbon receptor (AHR) co-occur with PAHs that are CYP1A inhibitors. This toxicity is mediated by the AHR2, and morpholino knockdown of CYP1A exacerbated toxicity. This study tested two hypotheses: 1) in the absence of functional CYP1A, metabolism of PAHs is shunted towards CYP1B1, which has been shown in mammals to produce more reactive metabolites of PAHs; alternatively 2) CYP1B1 serves a protective role …


Newspapers And Newspaper Ink Contain Agonists For The Ah Receptor, Jessica E. S. Bohonowych, Bin Zhao, Alicia R. Timme-Laragy, Dawoon Jung, Richard T. Di Giulio, Michael S. Denison Mar 2008

Newspapers And Newspaper Ink Contain Agonists For The Ah Receptor, Jessica E. S. Bohonowych, Bin Zhao, Alicia R. Timme-Laragy, Dawoon Jung, Richard T. Di Giulio, Michael S. Denison

Alicia R. Timme-Laragy

Ligand-dependent activation of the aryl hydrocarbon receptor (AhR) pathway leads to a diverse array of biological and toxicological effects. The best-studied ligands for the AhR include polycyclic and halogenated aromatic hydrocarbons, the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, as new AhR ligands are identified and characterized, their structural and physiochemical diversity continues to expand. Our identification of AhR agonists in crude extracts from diverse materials raises questions as to the magnitude and extent of human exposure to AhR ligands through normal daily activities. We have found that solvent extracts of newspapers from countries around the world stimulate the …


Newspapers And Newspaper Ink Contain Agonists For The Ah Receptor, Jessica E.S. Bohonowych, Bin Zhao, Alicia R. Timme-Laragy, Dawoon Jung, Richard T. Di Giulio, Michael S. Denison Dec 2007

Newspapers And Newspaper Ink Contain Agonists For The Ah Receptor, Jessica E.S. Bohonowych, Bin Zhao, Alicia R. Timme-Laragy, Dawoon Jung, Richard T. Di Giulio, Michael S. Denison

Alicia R. Timme-Laragy

Ligand-dependent activation of the aryl hydrocarbon receptor (AhR) pathway leads to a diverse array of biological and toxicological effects. The best-studied ligands for the AhR include polycyclic and halogenated aromatic hydrocarbons, the most potent of which is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, as new AhR ligands are identified and characterized, their structural and physiochemical diversity continues to expand. Our identification of AhR agonists in crude extracts from diverse materials raises questions as to the magnitude and extent of human exposure to AhR ligands through normal daily activities. We have found that solvent extracts of newspapers from countries around the world stimulate the …