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Final Progress Reports: University of Washington: Gene-Environment Interactions in Salmon Neurotoxicity

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Superfund Research Program

Gene-Environment Interactions in Salmon Neurotoxicity

Project Leader: Evan P. Gallagher
Grant Number: P42ES004696
Funding Period: 2006-2009

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Final Progress Reports

Year:   2008 

Coho salmon are an important ecological, recreational and economic species in the Western United States whose populations are in decline. Habitat impacts and chemical pollution are linked to declining salmon populations. Exposure to low levels of environmental chemicals representative of those encountered at Superfund sites can negatively interfere with behaviors that are critical to salmon survival. These behaviors include homing, prey detection, and predator avoidance. Studies conducted during the past year have yielded findings that extend the understanding of Superfund chemicals on salmon neurotoxic injury.

Using microarray analysis, Dr. Gallagher’s team of researchers demonstrated that copper, a common environmental contaminant that targets the fish olfactory system, disrupts molecular pathways and cellular signals associated with the detection of waterborne odorants. These impacts occur at low metal concentrations relevant to environmental exposures. Microarray studies yielded transcriptome fingerprints in salmon olfactory rosettes that will be of use for detecting neurobehavioral perturbations in Superfund field sites. The researchers also utilized zebrafish, a genetically well-defined laboratory model, to further define mechanisms of olfactory injury and chemical mixture interactions relevant to Superfund sites. Following exposure of adult zebrafish to copper and to the organophosphate chlorpyrifos (both as mixtures or as single agents), the researchers were able to confirm by microarrays that copper preferentially impacts g-protein coupled olfactory receptor signaling. In contrast, chlorpyrifos preferentially affects signal transduction. In the mixture exposures, the transcriptional signatures were most similar to copper alone, suggesting that the metal was driving the olfactory injury in the mixtures. Furthermore, gene expression profiles in zebrafish exposed to mixtures of copper and chlorpyrifos identified shared as well as unique genes relative to the individual constituents, indicating that one may be able to discriminate the contribution of metals from organophosphates on olfactory injury in fish at Superfund sites.

Dr. Gallagher’s experiments also led to the development of a quantitative PCR biomarker battery of approximately 25 genes that can be added to the group’s “toolkit” for analysis of toxic impacts on salmon as they migrate through Superfund sites. A subset of these markers was tested in collaboration with other SBRP investigators and USEPA Region 10 at a Pacific Northwest Superfund site that has undergone remediation. This multi-investigator project was designed to help the EPA test the use of sensitive exploratory markers of sediment-associated pollutants in ecological risk assessment. The biomarker results were consistent with chemical residue data reflecting low bioavailability to waterborne chemicals in salmon caged at the remediated site. Other studies conducted during the last year indicate that coho may have an increased sensitivity to the Superfund pesticide phorate during acclimation from low to high salinity.

In summary, there is a growing awareness that low exposures of environmental chemicals adversely affect salmon olfactory function and behavior. This project is significantly extending understanding of these issues from several perspectives, including; 1) identifying mechanisms of olfactory toxicity, 2) providing molecular tools for the detection of problematic sites and identifying affected animals, 3) dissecting mixture interactions, and 4) assessing the success of Superfund site remediation.

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