Characterization of an aryl hydrocarbon receptor from a cetacean : an approach for assessing contaminant susceptibility in protected species
Jensen, Brenda A.
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Some cetaceans bioaccumulate substantial concentrations of halogenated aromatic hydrocarbons (HAH) in their tissues, but little is known about the effects of such burdens on cetacean health. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related HAH cause toxicity via activation of the aryl hydrocarbon receptor (AHR), a member of the bHLH-PAS family of transcription factors. Differences in AHR structure and function are known to contribute to species-specific differences in susceptibility to HAH toxicity, and targets for HAH toxicity are related to the tissue-specific expression of AHR. The goal of these studies was to ascertain the potential for HAH effects in cetaceans by characterizing the AHR from the beluga, Delphinapterus leucas. The beluga AHR was characterized by its molecular structure, capacity for ligand binding, structure-binding relationships with various classes of HAH, as well as tissue-specific expression. These results show that: 1) in an in vitro system, the beluga AHR possesses binding affinities similar to AHRs of other mammals that are considered sensitive to toxic effects of HAH, 2) Structure-activity relationships are consistent with a common mechanism of coplanar HAH action among cetaceans and rodent species, and 3) the AHR protein is expressed in many tissues of the beluga, and is present at high levels in lymphoid organs, liver and lung. Together, these data suggest that cetaceans can be considered sensitive to the action of coplanar HAH. Further, using in vitro expressed proteins is a promising approach for addressing molecular and biochemical questions about PHAH toxicity in endangered and protected species where logistical and ethical concerns preclude testing in live animals.
Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution September 2000
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