Characterization of P-glycoprotein Expression as a Multixenobiotic Resistance Mechanism in Fish
Abstract
P-glycoproteins, responsible for multidrug resistance, function as energy dependent efflux flippases that prevent the cellular accumulation of moderately hydrophobic chemicals. 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. P-glycoprotein levels were elevated in tissue surrounding liver tumors in winter flounder (Pleuronectes americanus). Killifish (Fundulus heteroclitus) from a contaminated field sites had higher intestinal P-gp and lower hepatic P-gp than control killifish. P-glycoprotein was induced in fish by oil exposure but not by Beta-naphthoflavone or 2,3,7,8-tetrachlorodibenzofuran. Thus, 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 benzoApyrene (BaP) is a P-gp substrate. We show that BaP and/or its CYP1A metabolites are not transported by P-gp in liver, brain, or ovary.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2001
- Accession Number
- ADA397548
Entities
People
- Shannon M. Bard
Organizations
- Massachusetts Institute of Technology