Superfund Research Program
Developmental PAH Exposures in Fish: Mechanisms of Toxicity, Adaptation, and Later Life Consequences
Project Summary (2011-2017)
This project explores the effects of polycyclic aromatic hydrocarbons (PAHs) on development in an ecological context. The project includes studies of a population of killifish (Fundulus heteroditus) inhabiting a highly PAH-polluted estuary in Virginia, the Elizabeth River (ER) that includes a Superfund site. This population is highly resistant to the developmental impacts of PAHs occurring at this site and to laboratory exposures to specific PAHs, relative to killifish from uncontaminated sites. Thus the "Elizabeth River phenotype" provides an opportunity for studying evolutionary impacts of pollution, including mechanisms of adaptation and consequences of adaptation. And importunity, understanding mechanisms of adaptation provide insight into mechanisms of developmental toxicity of PAHs. Other studies with killifish from a reference site and with zebrafish explore specific mechanisms of PAH developmental toxicity, including effects on mitochondrial function and mtDNA damage, and the consequences of low level PAH exposures in embryos for later life stages. Consequences include explorations of tissue architecture; effects of later life exposures to other Center chemicals, and in collaboration with other Center projects and cores, neurobehavioral effects are emphasized. The overarching hypothesis of this project is that exposure to Superfund chemicals present at the ER Superfund site results in acute (e.g., teratogenesis and death) and chronic/multigenerational (e.g., cancer, altered behavior, population-level heritable changes) effects via mechanisms including oxidative stress, mitochondrial DNA damage, and altered AHR pathway function.
The specific aims of the project are:
- To determine the mechanisms underlying resistance to PAH-mediated embryo toxicity in the Elizabeth River population of killifish.
- To determine positive or negative consequences of this resistant phenotype.
- To determine the effects of PAHs and other chemicals of interest to the Center on mitochondrial DNA and mitochondrial function during embryonic development.
- To determine the later life consequences of low level PAH exposures to embryos, including alterations in tissue architecture, behavior, and responses to other stressors.