This project explores the effects of polycyclic aromatic hydrocarbons (PAHs) on development in an ecological context. The project will include studies of a population of killifish (Fundulus heteroclitus) 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 importantly, understanding mechanisms of adaptation will provide insight into mechanisms of developmental toxicity of PAHs, now becoming recognized as a critical target of this increasingly prevalent class of Superfund chemicals for both wildlife and human health. Other studies with killifish from a reference site and with zebrafish will 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 will 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 will be emphasized.
The specific aims of the project are: 1. To determine the mechanisms underlying resistance to PAH-mediated embryotoxicity in the Elizabeth River population of killifish. 2. To determine positive or negative consequences of this resistant phenotype. 3. To determine the effects of PAHs and other chemicals of interest to the Center on mitochondrial DNA and mitochondrial function during embryonic development. 4. To determine the later life consequences of low level PAH exposures to embryos.
These aims will be accomplished through a highly collaborative effort among a molecular toxicologist (Dr. Joel Meyer), a fish pathologist and ecotoxicologist (Dr. David Hinton) and an aquatic biochemical toxicologist (Dr. Richard Di Giulio).

Public Health Relevance

This project is highly relevant to the SBRP's themes of mechanisms of toxicity and susceptibility, gene-environment interactions, mixture effects, and ecological/evolutionary impacts of Superfund chemicals. Moreover, its focus on the sensitive process of vertebrate development reflects the theme of Duke's Superfund Center, which emphasizes substantive interactions among its biomedical and non-biomedical projects and support cores.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-SET-V)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
United States
Zip Code
Brown, Daniel R; Clark, Bryan W; Garner, Lindsey V T et al. (2015) Zebrafish cardiotoxicity: the effects of CYP1A inhibition and AHR2 knockdown following exposure to weak aryl hydrocarbon receptor agonists. Environ Sci Pollut Res Int 22:8329-38
Slotkin, Theodore A; Card, Jennifer; Seidler, Frederic J (2014) Prenatal dexamethasone, as used in preterm labor, worsens the impact of postnatal chlorpyrifos exposure on serotonergic pathways. Brain Res Bull 100:44-54
Levin, Edward D; Cauley, Marty; Johnson, Joshua E et al. (2014) Prenatal dexamethasone augments the neurobehavioral teratology of chlorpyrifos: significance for maternal stress and preterm labor. Neurotoxicol Teratol 41:35-42
Pillai, Hari K; Fang, Mingliang; Beglov, Dmitri et al. (2014) Ligand binding and activation of PPAR? by Firemaster® 550: effects on adipogenesis and osteogenesis in vitro. Environ Health Perspect 122:1225-32
Bess, Amanda S; Ryde, Ian T; Hinton, David E et al. (2013) UVC-induced mitochondrial degradation via autophagy correlates with mtDNA damage removal in primary human fibroblasts. J Biochem Mol Toxicol 27:28-41
Dong, Wu; Macaulay, Laura J; Kwok, Kevin W H et al. (2013) Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish: a tool for examining OH-BDE toxicity to early life stages. Aquat Toxicol 132-133:190-9
Slotkin, Theodore A; Cooper, Ellen M; Stapleton, Heather M et al. (2013) Does thyroid disruption contribute to the developmental neurotoxicity of chlorpyrifos? Environ Toxicol Pharmacol 36:284-7
Clark, Bryan W; Cooper, Ellen M; Stapleton, Heather M et al. (2013) Compound- and mixture-specific differences in resistance to polycyclic aromatic hydrocarbons and PCB-126 among Fundulus heteroclitus subpopulations throughout the Elizabeth River estuary (Virginia, USA). Environ Sci Technol 47:10556-66
Garner, Lindsey V T; Brown, Daniel R; Di Giulio, Richard T (2013) Knockdown of AHR1A but not AHR1B exacerbates PAH and PCB-126 toxicity in zebrafish (Danio rerio) embryos. Aquat Toxicol 142-143:336-46
Zhao, Bin; Bohonowych, Jessica E S; Timme-Laragy, Alicia et al. (2013) Common commercial and consumer products contain activators of the aryl hydrocarbon (dioxin) receptor. PLoS One 8:e56860

Showing the most recent 10 out of 198 publications