Date of Award

5-2014

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Environmental Toxicology

Advisor

Rice, Charles D

Committee Member

Bain , Lisa J

Committee Member

Baldwin , William S

Abstract

The southern branch of the Elizabeth River, at Portsmouth Virginia is one of the most polluted systems in North America. This harbor estuary system is also home to the Atlantic Wood Superfund site, which is heavily contaminated with creosote from the Atlantic Wood (AW) preservative company that ceased production in the later 1990s. Creosote is a mixture of polyaromatic hydrocarbons (PAHs), metals, and numerous aliphatic hydrocarbons, and well known to be carcinogenic. The toxicity of sediments and pore waters from the AW site has been studied extensively using Fundulus heteroclitus, also known as the mummichog, or Atlantic killifish. Most adult killifish from AW have hepatic lesions, ranging from focal hyperplasia to highly malignant tumors. As embryos and juveniles, these fish are resistant to developmental toxicity of PAHs relative to a reference population on King's Creek (KC) located near Mobjack Bay on the York River. Moreover, the resistance of AW fish to developmental toxicity is associated with altered aryl-hydrocarbon receptor (AhR) functions and signaling, leading to recalcitrance in CYP1A induction by PAHs. To determine the potential of AW sediment pore water to modulate immune functions in mammals, this study used the mouse macrophage cell line RAW264.7 as a model for pro-inflammatory functions. Compared to KC sediment pore water, AW pore water induces more iNOS and COX-2 protein expression, nitric oxide and IL-6 secretion, in RAW264.7 cells. This enhanced pro-inflammatory property of AW extracts is due, in large part, to high levels of endotoxin, as polymyxin-B ameliorates this property. Moreover, AW sediment extracts have quantitatively higher endotoxin as measures by the limulus lysate assay.

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