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
- Project Summary
Human populations and biological communities at or near Superfund sites are potentially chronically exposed to high levels of mixtures of contaminants including PCBs, dioxins, PAHs and metals. The Hudson River Estuary contains Superfund sites for PCBs, dioxin, and several heavy metals. Fish populations from several Atlantic coast estuaries that are highly contaminated with these chemicals, including Atlantic tomcod from the Hudson River, exhibit resistance to increased mortality, early life-stage developmental abnormalities, and induction of genes critical to metabolism of these compounds. Toxic responses to PCBs, dioxins, and PAHs are all believed to be mediated by the aryl hydrocarbon receptor (AHR) pathway. The researchers have used Atlantic tomcod from the Hudson River (HR) Estuary as a model to explore the molecular basis of the resistance phenotype to better understand the persistence of this response and its ramifications on the ecosystem level.
It was previously demonstrated that tomcod from the Hudson River are highly resistant at early life stage toxic endpoints to coplanar PCBs and dioxin, but those from the cleaner Miramichi River, New Brunswick, and Shinnecock Bay, New York, are sensitive to these compounds. Recent studies indicate that tomcod from the Hudson River and Miramichi River are equally sensitive to cytochrome P4501A1 gene induction by an environmentally relevant PAH, benzo[a]pyrene (B[a]P), suggesting that the mechanistic basis for toxicity in tomcod to PCBs/dioxin and PAHs are almost certainly different and probably involve AHR-dependent and AHR-independent mechanisms. This is one of the first demonstrations of different mechanisms to toxicity in animals treated with halogenated aromatic compounds such as PCBs and dioxin compared to non-halogenated aromatic compounds such as PAHs.
Project researchers continued to investigate the mechanistic basis of resistance in tomcod by characterizing and comparing the structure and expression of individual components of the AHR pathway; AHR2, ARNT2 (aryl receptor nuclear translocator2) and AHRR (AHR repressor) in tomcod from the Hudson River and two sensitive populations. Although no significant differences in the expression of these genes were observed at the transcriptional level that would explain resistance phenotype, a potentially interesting genetic variant in AHR2 was found. A two amino acid deletion was observed in what may be a functionally important part of AHR2. The deletion was observed in all tomcod from the Hudson River and was absent in tomcod from Shinnecock Bay and Miramichi River (n=10 fish/river). Interestingly, only one other base substitution (and that was silent) among the complete AHR2 cDNA in these 30 fish indicated the functional importance of AHR2 and potential significance of the variant. The variant allele will be evaluated in a variety of assays to assess its functional importance.
The researchers also investigated the geographic distribution of resistance in the Hudson River population and its costs to the Hudson River ecosystem. Other examples of resistance in vertebrates have always been limited to very small populations occupying limited geographic locales. They demonstrated that virtually the entire tomcod population occupying 90 miles of the Hudson River is highly resistant to PCB-77, but not a PAH (BaP) making it the most spatially extensive resistant vertebrate population ever reported. They have also demonstrated that because tomcod is the only species to spawn during the winter months their young life stages are dominant prey in the Hudson River food chain during the following summer. Thus, resistance, which allows the bioaccumulation of high levels of persistent PCBs and dioxins combined with the critical role of tomcod in the Hudson River food chain, may have important costs to the Hudson River ecosystem.