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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010356-12
Application #
8450241
Study Section
Special Emphasis Panel (ZES1-SET-V)
Project Start
Project End
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
12
Fiscal Year
2013
Total Cost
$389,570
Indirect Cost
$161,917
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Oliveri, Anthony N; Ortiz, Erica; Levin, Edward D (2018) Developmental exposure to an organophosphate flame retardant alters later behavioral responses to dopamine antagonism in zebrafish larvae. Neurotoxicol Teratol 67:25-30
Slotkin, Theodore A; Skavicus, Samantha; Seidler, Frederic J (2018) Developmental neurotoxicity resulting from pharmacotherapy of preterm labor, modeled in vitro: Terbutaline and dexamethasone, separately and together. Toxicology 400-401:57-64
Lefèvre, Emilie; Bossa, Nathan; Gardner, Courtney M et al. (2018) Biochar and activated carbon act as promising amendments for promoting the microbial debromination of tetrabromobisphenol A. Water Res 128:102-110
Kollitz, Erin M; Kassotis, Christopher D; Hoffman, Kate et al. (2018) Chemical Mixtures Isolated from House Dust Disrupt Thyroid Receptor ? Signaling. Environ Sci Technol :
Hartman, Jessica H; Smith, Latasha L; Gordon, Kacy L et al. (2018) Swimming Exercise and Transient Food Deprivation in Caenorhabditis elegans Promote Mitochondrial Maintenance and Protect Against Chemical-Induced Mitotoxicity. Sci Rep 8:8359
Luz, Anthony L; Kassotis, Christopher D; Stapleton, Heather M et al. (2018) The high-production volume fungicide pyraclostrobin induces triglyceride accumulation associated with mitochondrial dysfunction, and promotes adipocyte differentiation independent of PPAR? activation, in 3T3-L1 cells. Toxicology 393:150-159
Day, D B; Xiang, J; Mo, J et al. (2018) Combined use of an electrostatic precipitator and a high-efficiency particulate air filter in building ventilation systems: Effects on cardiorespiratory health indicators in healthy adults. Indoor Air 28:360-372
Slotkin, Theodore A; Ko, Ashley; Seidler, Frederic J (2018) Does growth impairment underlie the adverse effects of dexamethasone on development of noradrenergic systems? Toxicology 408:11-21
Rock, Kylie D; Horman, Brian; Phillips, Allison L et al. (2018) EDC IMPACT: Molecular effects of developmental FM 550 exposure in Wistar rat placenta and fetal forebrain. Endocr Connect 7:305-324
Weinhouse, Caren; Truong, Lisa; Meyer, Joel N et al. (2018) Caenorhabditis elegans as an emerging model system in environmental epigenetics. Environ Mol Mutagen 59:560-575

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