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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

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 …