Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Internet Explorer is no longer a supported browser.

This website may not display properly with Internet Explorer. For the best experience, please use a more recent browser such as the latest versions of Google Chrome, Microsoft Edge, and/or Mozilla Firefox. Thank you.

Your Environment. Your Health.

Progress Reports: Boston University: Mechanisms and Impacts of PCB Resistant Fish

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
View this project in the NIH Research Portfolio Online Reporting Tools (RePORT)

Learn More About the Grantee

Visit the grantee's eNewsletter page Visit the grantee's eNewsletter page Visit the grantee's Twitter page View the grantee's Factsheet(377KB)

Progress Reports

Year:   2019  2018  2017  2016  2015  2014  2013  2012  2010  2009  2008  2007  2006  2005  2004  2003  2002  2001  2000  1999  1998  1997  1996  1995 

The overall objective of this project is to understand the mechanisms underlying differential sensitivity to the developmental toxicity of dioxins. Project investigators are addressing this question by elucidating the differences in the expression and function of two distinct aryl hydrocarbon receptors (AHR1 and AHR2) and an AHR repressor during development, using a fish model of dioxin sensitivity and resistance. Previously, a population of the estuarine teleost Fundulus heteroclitus from New Bedford Harbor (NBH) has been characterized. The researchers showed that these fish were approximately 15-fold less sensitive to TCDD than F. heteroclitus from a reference site, Scorton Creek, Sandwich, MA (SC). To investigate the role of the aryl hydrocarbon receptor (AHR) signal transduction pathway in this dioxin resistance, scientists measured the relative levels of AHR1, AHR2, and ARNT2 mRNA in tissues of adult fish from SC and NBH. Adult SC fish expressed AHR2 and ARNT2 mRNA in all tissues examined, while AHR1 was expressed predominantly in brain, heart, and gonad. In contrast, AHR1 mRNA was widely expressed in NBH fish, appearing with unusual abundance in gill, gut, kidney, liver, and spleen. This AHR1 expression pattern was not observed in the lab-reared progeny of NBH fish, demonstrating that constitutive AHR1 expression in gill, gut, kidney, liver, and spleen is not a heritable phenotype. Furthermore, widespread AHR1 expression was not induced in reference-site fish by TCDD or PCB mixtures, suggesting that aberrant AHR1 expression is not simply a normal physiological response to contaminant exposure.

Evidence for altered regulation of AHR1 in New Bedford fish prompted the investigators to sequence multiple clones from the NBH and SC populations. These studies identified an AHR1 polymorphism in Fundulus, involving at least two AHR1 alleles that differ at 8 amino acids (of 942). A survey of the two populations showed that the two AHR1 alleles are present at approximately equal frequencies in the reference population, whereas one allele predominates (95%) in NBH fish. When the two AHR1 alleles were expressed in vitro, they did not differ in their TCDD-binding affinity. Current efforts are underway to explore possible allele-specific differences in other functions.

Another possible mechanism for the dioxin resistance of NBH fish is the enhanced expression of a repressor of AHR function. One such repressor, denoted AHR repressor (AHRR), has been identified in mice (Mimura et al., 1999, Genes Dev.). Using RT-PCR with degenerate primers, we cloned and sequenced an AHRR homolog from Fundulus (FhAHRR). Preliminary RT-PCR analyses indicate that FhAHRR expression is not altered in the adult resistant fish, on a whole tissue basis. However, FhAHRR expression is induced by TCDD treatment of reference fish. Future studies will examine the interaction of FhAHRR and AHR1 and AHR2 using transfection of mammalian cells.

Back
to Top