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)
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Raftery, Tara D; Jayasundara, Nishad; Di Giulio, Richard T (2017) A bioenergetics assay for studying the effects of environmental stressors on mitochondrial function in vivo in zebrafish larvae. Comp Biochem Physiol C Toxicol Pharmacol 192:23-32
Mu, Jingli; Chernick, Melissa; Dong, Wu et al. (2017) Early life co-exposures to a real-world PAH mixture and hypoxia result in later life and next generation consequences in medaka (Oryzias latipes). Aquat Toxicol 190:162-173
Slotkin, Theodore A; Skavicus, Samantha; Card, Jennifer et al. (2017) In vitro models reveal differences in the developmental neurotoxicity of an environmental polycylic aromatic hydrocarbon mixture compared to benzo[a]pyrene: Neuronotypic PC12 Cells and embryonic neural stem cells. Toxicology 377:49-56
Luz, Anthony L; Godebo, Tewodros R; Smith, Latasha L et al. (2017) Deficiencies in mitochondrial dynamics sensitize Caenorhabditis elegans to arsenite and other mitochondrial toxicants by reducing mitochondrial adaptability. Toxicology 387:81-94
Hartman, Jessica H; Kozal, Jordan S; Di Giulio, Richard T et al. (2017) Zebrafish have an ethanol-inducible hepatic 4-nitrophenol hydroxylase that is not CYP2E1-like. Environ Toxicol Pharmacol 54:142-145
Meyer, Joel N; Chan, Sherine S L (2017) Sources, mechanisms, and consequences of chemical-induced mitochondrial toxicity. Toxicology 391:2-4
Slotkin, Theodore A; Skavicus, Samantha; Seidler, Frederic J (2017) Diazinon and parathion diverge in their effects on development of noradrenergic systems. Brain Res Bull 130:268-273
Lindberg, C D; Jayasundara, N; Kozal, J S et al. (2017) Resistance to polycyclic aromatic hydrocarbon toxicity and associated bioenergetic consequences in a population of Fundulus heteroclitus. Ecotoxicology 26:435-448
Abreu-Villa├ža, Yael; Levin, Edward D (2017) Developmental neurotoxicity of succeeding generations of insecticides. Environ Int 99:55-77
Jayasundara, Nishad; Fernando, Pani W; Osterberg, Joshua S et al. (2017) Cost of Tolerance: Physiological Consequences of Evolved Resistance to Inhabit a Polluted Environment in Teleost Fish Fundulus heteroclitus. Environ Sci Technol 51:8763-8772

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