Cultured Fish Cells as Model System for Studying Mechanisms of Dioxin Toxicity

EPA Grant Number: R823889
Title: Cultured Fish Cells as Model System for Studying Mechanisms of Dioxin Toxicity
Investigators: Hahn, Mark E. , Stegeman, John J.
Institution: Woods Hole Oceanographic Institution
EPA Project Officer: Manty, Dale
Project Period: July 1, 1995 through June 1, 1997
Project Amount: $252,790
RFA: Exploratory Research - Environmental Biology (1995) RFA Text |  Recipients Lists
Research Category: Biology/Life Sciences , Health , Ecosystems

Description:

The overall objective of the proposed research is to understand the biochemical mechanisms of dioxin toxicity in fish, especially as it relates to normal cellular physiology and the control of cell proliferation and differentiation. Assessment of the risk posed by the presence of dioxins and related halogenated aromatic hydrocarbons (HAH) in aquatic environments is hindered by the lack of knowledge concerning the mechanism by which these compounds produce toxicity in fish and other aquatic animals. In addition, there is uncertainty as to the relative contribution of individual HAH congeners to the aggregate HAH risk, a poor understanding of interactive effects that may occur in HAH mixtures, and incomplete knowledge of the relationship of proximal biochemical changes (such as induction of cytochrome P450) to more distal, "toxic" effects. These uncertainties suggest the need for model systems in which to address questions regarding the mechanisms of HAH toxicity to aquatic species. The present studies will use a well-defined model system (a fish hepatoma cell line) and well-defined biochemical pathway and associated responses (aryl hydrocarbon receptor-mediated induction of cytochrome P450) to determine the role of cellular differentiation state in influencing the response to dioxin exposure, and to assess the effect of dioxins on cell proliferation and differentiation in fish. A more complete understanding of the mechanism of dioxin toxicity to fish and other aquatic animals will be important for efforts to assess the risks of dioxin contamination to aquatic ecosystems.

Publications and Presentations:

Publications have been submitted on this project: View all 16 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 12 journal articles for this project

Supplemental Keywords:

RFA, Scientific Discipline, Toxics, Ecosystem Protection/Environmental Exposure & Risk, exploratory research environmental biology, Environmental Chemistry, Ecosystem/Assessment/Indicators, Chemical Mixtures - Environmental Exposure & Risk, Ecosystem Protection, Chemistry, HAPS, pesticides, Monitoring/Modeling, Ecological Effects - Environmental Exposure & Risk, Ecological Effects - Human Health, Biology, Ecological Indicators, ecological exposure, ecological risk assessment, aquatic ecosystem, fate and transport, environmental monitoring, dioxin, ecosystem assessment, chemical characteristics, cytochrome P450, hydrocarbon, exposure, cell physiology, HAH, biomonitoring, toxicity, aquatic ecosystems, dioxin toxicity, hydrocarbons, fish , cultured fish cells, dioxin exposure

Progress and Final Reports:

Final Report