Project Summary (1995-2000)

The overall objective of the research is to understand the mechanisms of animal sensitivity and resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons (PHAH), especially resistance developing after long-term exposure associated with hazardous waste sites. Studies are being conducted using the teleost Fundulus heteroclitus, which has been shown to develop TCDD resistance and possesses a number of other advantages as a vertebrate model for chemical resistance. Differential PHAH sensitivity/resistance is being examined in populations of F. heteroclitus inhabiting New Bedford Harbor and other sites. The hypothesis that alterations in the AhR-dependent signal transduction pathway underlie the development of resistance is being addressed by examining key steps in the pathway between receptor binding and changes in gene expression. The field- and laboratory-based studies will provide a link between biomedical and ecological aspects of research on the impact of Superfund sites, enhancing the development of fish as sentinel species, and the identification of vertebrate markers of genetic susceptibility associated with increased health risks in populations and subpopulations exposed to toxic waste.