Publication Date:
2022-05-25
Description:
Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Aquatic Toxicology 76 (2006): 295-305, doi:10.1016/j.aquatox.2005.10.005.
Description:
Marine mammals respond to the presence of polycyclic and planar
halogenated aromatic hydrocarbons (PAH or PHAH) with the induced expression
in endothelium of cytochrome P4501A1, regulated through the aryl hydrocarbon
receptor (AHR) transcription factor. Physiological responses in other animals,
such as edema and inflammation indicate that the endothelium may be
compromised by exposure to AHR agonists, which are ubiquitous in the marine
environment. In other mammals and fish the cellular and molecular
consequences of exposure to AHR agonists have been elucidated in cultured
endothelial cells. We have cultured and characterized cetacean endothelial cells
(EC) and used them in induction studies. Endothelial cells were cultured from the
lung and kidney of the bottlenose dolphin Tursiops truncatus and exposed to the
AHR agonists β-naphthoflavone (βNF) and 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD). βNF (1-3 μM) induced significant increases in CYP1A1(O-deethylation
of 7-ethoxyresorufin to resorufin;EROD) activity to 3.6 and 0.92 pmol/mg/min in
lung and kidney EC, respectively. TCDD was more potent than βNF, and more
efficacious, with maximum induction of CYP1A1activity of 10.1 and 15.2
pmol/mg/min in lung and kidney EC at 3-10 nM TCDD. The differential response
indicates that the lung and kidney endothelial cells in culture retain the ability to
respond in a selective manner to specific stimuli. Both the molecular mechanisms
of induction and the physiological consequences, especially in the vasculature, of
toxicant exposure can be studied in this system.
Description:
Part of this work was completed during a faculty fellowship from Fordham
University for RAG. The Faculty Research Council of Fordham University
provided partial support for RAG. This research was supported by NIH grant 5-
P42-ES07381 and by U.S.EPA grant R827102-01-0. This research is an
outgrowth and continuing impact of Sea Grant Number Grant No. NA90-
AA-D-SG480, project NA86RG0075-R/P61.
Keywords:
Endothelium
;
CYP1A
;
EROD
;
Dioxin
;
Cetacean
;
Microvascular
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
Format:
850302 bytes
Format:
application/pdf
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