Publication Date:
2022-05-25
Description:
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
Description:
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.
Description:
This work was supported by NIH Grant No. ES06272, NOAA National Sea Grant
College Program Grant Nos. NA46RG0470, (WHO! Sea Grant Project No. R/B-137),
NA86RG0075 (WHO! Sea Grant Project No. R/B-15l), NA86RG0075 (WHOI Sea
Grant Project No. R/P-64) and the Ocean Ventures Fund.
Keywords:
Marine pollution
Repository Name:
Woods Hole Open Access Server
Type:
Thesis
Format:
application/pdf
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