{"id":{"repo_id":"woods-hole","oai_identifier":"oai:darchive.mblwhoilibrary.org:1912/3537"},"canonical_url":"https://search.dev.ndltd.org/etd/woods-hole/oai:darchive.mblwhoilibrary.org:1912/3537","repository":{"repo_id":"woods-hole","name":"Woods Hole Oceanographic Institute","base_url":"https://darchive.mblwhoilibrary.org/server/oai/request"},"display":{"title":"Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish","abstract":"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 especially in liver, brain, and ovary. Using this assay, we assessed whether the common environmental contaminant and carcinogen benzo(a)pyrene (B[a]P) is a P-gp substrate. We show that B[a]P and/or its CYP1A metabolites are not transported by P-gp in liver, brain, or ovary.","abstract_html":"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 especially in liver, brain, and ovary. Using this assay, we assessed whether the common environmental contaminant and carcinogen benzo(a)pyrene (B[a]P) is a P-gp substrate. We show that B[a]P and/or its CYP1A metabolites are not transported by P-gp in liver, brain, or ovary.","abstract_has_math":false,"creators":["Bard, Shannon Mala"],"institution":"Massachusetts Institute of Technology and Woods Hole Oceanographic Institution","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2000,"date_issued":"2000-10","date_published":"2000-10","updated_at":"2026-07-27T22:05:18Z","subjects":["P-glycoprotein","Multidrug resistance","Xenobiotics","Fish"],"languages":["en_US"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.1575/1912/3537"],"render_values":[{"text":"10.1575/1912/3537","href":"https://doi.org/10.1575/1912/3537","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/1912/3537","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Bard, Shannon Mala"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2010-05-26T19:40:12Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-05-26T19:40:12Z"]},{"key":"dc:date.issued","label":"Date","values":["2000-10"]},{"key":"dc:publisher","label":"Institution","values":["Massachusetts Institute of Technology and Woods Hole Oceanographic Institution"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["P-glycoprotein","Multidrug resistance","Xenobiotics","Fish"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.1575/1912/3537"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1912/3537"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["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"]},{"key":"dc:description.abstract","label":"Abstract","values":["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 especially in liver, brain, and ovary. Using this assay, we assessed whether the common environmental contaminant and carcinogen benzo(a)pyrene (B[a]P) is a P-gp substrate. We show that B[a]P and/or its CYP1A metabolites are not transported by P-gp in liver, brain, or ovary."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish"]}]}],"canonical_facts":{"dc:creator":["Bard, Shannon Mala"],"dc:date.accessioned":["2010-05-26T19:40:12Z"],"dc:date.available":["2010-05-26T19:40:12Z"],"dc:date.issued":["2000-10"],"dc: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"],"dc:description.abstract":["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 especially in liver, brain, and ovary. Using this assay, we assessed whether the common environmental contaminant and carcinogen benzo(a)pyrene (B[a]P) is a P-gp substrate. We show that B[a]P and/or its CYP1A metabolites are not transported by P-gp in liver, brain, or ovary."],"dc:format.mimetype":["application/pdf"],"dc:identifier.doi":["10.1575/1912/3537"],"dc:identifier.uri":["https://hdl.handle.net/1912/3537"],"dc:language.iso":["en_US"],"dc:publisher":["Massachusetts Institute of Technology and Woods Hole Oceanographic Institution"],"dc:subject":["P-glycoprotein","Multidrug resistance","Xenobiotics","Fish"],"dc:title":["Characterization of P-glycoprotein expression as a multixenobiotic resistance mechanism in fish"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T22:05:18Z"}