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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
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 …
Synergistic Induction Of Ahr Regulated Genes In Developmental Toxicity From Co-Exposure To Two Model Pahs In Zebrafish, Alicia R. Timme-Laragy, Crystal J. Cockman, Cole W. Matson, Richard T. Di Giulio
Synergistic Induction Of Ahr Regulated Genes In Developmental Toxicity From Co-Exposure To Two Model Pahs In Zebrafish, Alicia R. Timme-Laragy, Crystal J. Cockman, Cole W. Matson, Richard T. Di Giulio
Alicia R. Timme-Laragy
Polycyclic aromatic hydrocarbons (PAHs) are pollutants created by the incomplete combustion of carbon, and are increasing in the environment largely due to the burning of fossil fuels. PAHs occur as complex mixtures, and some combinations have been shown to cause synergistic developmental toxicity in fish embryos, characterized by pericardial edema and craniofacial malformations. Previous studies have indicated that in the zebrafish model, this toxicity is mediated by the aryl hydrocarbon receptor 2 (AHR2), and enhanced by inhibition of CYP1A activity. In this study, we further examined this interaction of the model PAH and AHR agonist β-naphthoflavone (BNF) with and without …