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
To investigate mechanisms for dioxin resistance in killifish, project investigators cloned and sequenced a killifish homolog of a mouse gene known as AHR repressor (AHRR). This protein inhibited the ability of dioxin to cause AHR1- or AHR2-dependent changes in gene expression. Additionally, the synthesis of AHRR was increased by treatment with dioxins or PCBs in an AHR-dependent manner. However, the expression of the AHRR gene was not increased in the dioxin-resistant New Bedford Harbor (NBH) fish.
Another possible resistance mechanism involves polymorphisms in AHR genes. We have identified 24 polymorphic sites among 7 AHR1 cDNA clones. The 7 alleles cluster in two groups (AHR1*1 and AHR1*2). Screening of NBH and control fish showed that the AHR1*1A and AHR1*1B alleles are under-represented in the NBH population, suggesting selection against fish possessing these alleles. We have begun to investigate the function of these alleles; initial results indicate that both proteins exhibit high-affinity binding of dioxins and can support dioxin-dependent activation of gene expression. Project investigators are now beginning a detailed survey of the structure and function of these alleles at NBH and other sites.