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New York University School of Medicine

Superfund Research Program

Mechanisms of Resistance of Aquatic Vertebrate Populations to Mixtures of Aromatic Hydrocarbons and Metal Contaminants

Project Leader: Isaac I. Wirgin
Grant Number: P42ES010344
Funding Period: 2000 - 2006

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Project Summary (2000-2006)

The goal of this study is to investigate the mechanistic bases of non-inducibility of cytochrome P4501A1 (CYP1A1) in Atlantic tomcod (Microgadus tomcod) that have been exposed to heavy metals and polycyclic aromatic hydrocarbons (PAHs). The hypothesis is that CYP1A1 transcription is inhibited by down-regulation of the aromatic hydrocarbon receptor (AhR) pathway in tomcod and other vertebrate species found at Superfund sites. Because AhR expression is critical to normal liver development and immunosurveillance in the absence of aromatic hydrocarbons, down-regulation of AhR may have profound effects on population and community well being after remediation of Superfund sites. Researchers are determining if impaired inducibility of CYP1A1 is a genetic adaptation or a single generation physiological acclimation. Recently developed tomcod AhR probes are being used to compare the effects of chemical treatment and environmental exposure on expression of AhR MRNA and protein in tomcod from the Hudson River and a cleaner reference river in Canada. Additionally, the epigenetic effects of metals-induced methylation on expression of CYP1A1 are being investigated in tomcod. Previously identified tomcod AhR variants are being characterized and their functional significance evaluated with environmentally relevant concentrations of PCBs and PAHs. Finally, a tomcod homologue of the recently described AhR repressor and its functional role in the response of populations to Superfund contaminants will be evaluated.

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