Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish
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 October 2000 Transmembrane P-glycoproteins (P-gps) are responsible for multidrug resistance (MDR) phenotypes in tumor...
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Massachusetts Institute of Technology and Woods Hole Oceanographic Institution
2000
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ftwhoas:oai:darchive.mblwhoilibrary.org:1912/3537 2023-05-15T15:15:47+02:00 Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish Bard, Shannon Mala Arctic 2000-10 application/pdf https://hdl.handle.net/1912/3537 en_US eng Massachusetts Institute of Technology and Woods Hole Oceanographic Institution WHOI Theses https://hdl.handle.net/1912/3537 doi:10.1575/1912/3537 doi:10.1575/1912/3537 P-glycoprotein Multidrug resistance Xenobiotics Fish Thesis 2000 ftwhoas https://doi.org/10.1575/1912/3537 2022-05-28T22:58:00Z 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 October 2000 Transmembrane P-glycoproteins (P-gps) are responsible for multidrug resistance (MDR) phenotypes in tumor cell lines. P-glycoproteins function as energy dependent efflux flippases that prevent the cellular accumulation of a wide variety of compounds. We characterized P-gp expression in populations of several fish species exposed in their natural habitat to environmental contaminants which may be P-gp substrates/inducers. We evaluated whether P-gp activity may be implicated in this multixenobiotic resistant phenotype. In winter flounder (Pleuronectes americanus) with contaminant-associated liver tumors, P-gp was highly expressed in bile canaliculi of non-tumorous liver surrounding cholangiocellular carcinoma, but was not detected within tumors. Cellular stress caused by impaired bile elimination may be responsible for elevated P-gp. Killifish (Fundulus heteroclitus) from a contaminated field sites had higher intestinal P-gp and lower hepatic P-gp than control killifish. In contaminated fish, elevated intestinal P-gp may provide a barrier against absorption of P-gp substrates/inducers thus limiting the amount of these compounds exported to the liver. We investigated whether P-gp might be involved in induction of cytochrome P4501A (CYPIA). Although CYPIA and P-gp were both elevated in oil exposed blennies (Anoplarchus purpurescens), there was no induction of P-gp in blennies exposed to ß-naphthoflavone nor in killfish exposed to 2,3,7,8-tetrachlorodibenzofuran, both CYPIA inducer. Thus in fish, P-gp expression is not regulated by the aryl hydrocarbon receptor pathway. We developed a protocol for an in vivo assay to simultaneously evaluate P-gp mediated transport of a model substrate, rhodamine B (rhB), in multiple organs of killifish. Our results indicate that P-gps play a major role in transport of xenobiotics in fish ... Thesis Arctic Woods Hole Scientific Community: WHOAS (Woods Hole Open Access Server) Arctic Woods Hole, MA |
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Woods Hole Scientific Community: WHOAS (Woods Hole Open Access Server) |
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language |
English |
topic |
P-glycoprotein Multidrug resistance Xenobiotics Fish |
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P-glycoprotein Multidrug resistance Xenobiotics Fish Bard, Shannon Mala Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish |
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P-glycoprotein Multidrug resistance Xenobiotics Fish |
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 October 2000 Transmembrane P-glycoproteins (P-gps) are responsible for multidrug resistance (MDR) phenotypes in tumor cell lines. P-glycoproteins function as energy dependent efflux flippases that prevent the cellular accumulation of a wide variety of compounds. We characterized P-gp expression in populations of several fish species exposed in their natural habitat to environmental contaminants which may be P-gp substrates/inducers. We evaluated whether P-gp activity may be implicated in this multixenobiotic resistant phenotype. In winter flounder (Pleuronectes americanus) with contaminant-associated liver tumors, P-gp was highly expressed in bile canaliculi of non-tumorous liver surrounding cholangiocellular carcinoma, but was not detected within tumors. Cellular stress caused by impaired bile elimination may be responsible for elevated P-gp. Killifish (Fundulus heteroclitus) from a contaminated field sites had higher intestinal P-gp and lower hepatic P-gp than control killifish. In contaminated fish, elevated intestinal P-gp may provide a barrier against absorption of P-gp substrates/inducers thus limiting the amount of these compounds exported to the liver. We investigated whether P-gp might be involved in induction of cytochrome P4501A (CYPIA). Although CYPIA and P-gp were both elevated in oil exposed blennies (Anoplarchus purpurescens), there was no induction of P-gp in blennies exposed to ß-naphthoflavone nor in killfish exposed to 2,3,7,8-tetrachlorodibenzofuran, both CYPIA inducer. Thus in fish, P-gp expression is not regulated by the aryl hydrocarbon receptor pathway. We developed a protocol for an in vivo assay to simultaneously evaluate P-gp mediated transport of a model substrate, rhodamine B (rhB), in multiple organs of killifish. Our results indicate that P-gps play a major role in transport of xenobiotics in fish ... |
format |
Thesis |
author |
Bard, Shannon Mala |
author_facet |
Bard, Shannon Mala |
author_sort |
Bard, Shannon Mala |
title |
Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish |
title_short |
Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish |
title_full |
Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish |
title_fullStr |
Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish |
title_full_unstemmed |
Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish |
title_sort |
characterization of p-glycoprotein expression as a multixenobiotic resistance mechanism in fish |
publisher |
Massachusetts Institute of Technology and Woods Hole Oceanographic Institution |
publishDate |
2000 |
url |
https://hdl.handle.net/1912/3537 |
op_coverage |
Arctic |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
doi:10.1575/1912/3537 |
op_relation |
WHOI Theses https://hdl.handle.net/1912/3537 doi:10.1575/1912/3537 |
op_doi |
https://doi.org/10.1575/1912/3537 |
op_publisher_place |
Woods Hole, MA |
_version_ |
1766346128793534464 |