Superfund Research Program
Mechanisms and Impacts of PCB Resistant Fish
Project Leader: Mark E. Hahn (Woods Hole Oceanographic Institution)
Co-Investigators: Sibel I. Karchner (Woods Hole Oceanographic Institution), Neelakanteswar Aluru (Woods Hole Oceanographic Institution)
Grant Number: P42ES007381
Funding Period: 1995-2020
The overall objective of this project is to understand the impact of long-term, multi-generational exposure to high levels of dioxin-like chemicals, including certain polychlorinated biphenyls (PCBs). To address this problem, project investigators are studying a population of estuarine fish, Atlantic killifish (Fundulus heteroclitus), inhabiting New Bedford Harbor, MA (NBH), a Superfund site that is highly contaminated with PCBs and other chemicals. Previously, they showed that NBH killifish are approximately 14-fold less sensitive to dioxin-like compounds than killifish from a reference site, Scorton Creek, in Sandwich, MA (SC), and that this "dioxin resistance" is heritable. In addition to increasing understanding of how natural populations of animals respond to high-level contaminant exposure, this research uses fish as models to investigate the mechanisms underlying differential sensitivity to the developmental toxicity of dioxin-like chemicals.
In fish, as in mammals, the toxic and biochemical effects of dioxin-like chemicals occur through the interaction of these chemicals with the aryl hydrocarbon receptor (AHR), leading to altered gene expression. Project investigators have identified two distinct aryl hydrocarbon receptors (AHR1 and AHR2) in killifish and other species of fish. The specific objective of research in this project is to determine the role of these two receptors--as well as other proteins in the AHR signaling pathway--in the dioxin/PCB resistance that has evolved in NBH fish.
This year, the researchers continued to investigate two possible mechanisms of resistance. First, they expanded studies of the AHR repressor (AHRR), a protein that can inhibit AHR signaling, and confirmed that expression of the AHRR is inducible by dioxin-like compounds in wild-type (reference) killifish. The project investigators found that two different populations of resistant killifish (the dioxin-resistant population from NBH and a polynuclear aromatic hydrocarbon (PAH)-resistant population from the Elizabeth River, VA) share the same phenotype involving a lack of AHRR inducibility. Thus, some aspects of the mechanism of resistance may be similar among resistant populations. However, altered AHRR expression does not appear to explain the resistant phenotype.
The investigators also obtained additional information on the possible role of AHR gene polymorphisms (multiple forms of the gene that lead to variant AHR proteins) in the mechanism of resistance. They identified additional AHR1 polymorphisms and confirmed a difference in allele frequencies between NBH and SC fish. However, they also showed that the predominant alleles in NBH and SC fish do not differ functionally. Recently, they have identified polymorphisms in the AHR2 gene that could play a role in the resistant phenotype. These AHR2 polymorphisms are in the process of being characterized more fully.
Understanding how dioxin/PCB resistance occurs in these highly-exposed fish will improve the ability to predict the sensitivity of humans and wildlife to these compounds. In addition, this research will help us understand the long-term impact of chemicals at this and other Superfund sites.