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Induction and Inhibition of P450 Expression in Piscine Species: Implications for Biomarker Determination and Toxicity

EPA Grant Number: U915004
Title: Induction and Inhibition of P450 Expression in Piscine Species: Implications for Biomarker Determination and Toxicity
Investigators: Levin, Steven L.
Institution: Miami University
EPA Project Officer: McClure, Karen
Project Period: January 1, 1996 through August 17, 1998
Project Amount: $102,000
RFA: STAR Graduate Fellowships (1996)
Research Category: Fellowship - Toxicology , Health Effects , Academic Fellowships

Description:

Objective:

The objective of this research project is to gain an understanding of the relationship between P4501A mRNA levels and P4501A catalytic rates to determine the utility of P4501A mRNA levels as a biomarker of environmental contamination.

Approach:

This research project characterized the relationship between: (1) hepatic (liver) P4501A mRNA levels and catalytic activity between the detritivorous gizzard shad and the carnivorous rainbow trout following waterborne exposure to a model P4501A class inducer; (2) catalytic activity between gills and livers—the former having direct contact with the external environment and the latter having indirect contact with the external environment; and (3) P4501A mRNA levels and catalytic activity following exposure to an inhibitor of P4501A catalytic activity. To conduct a practical assessment of induction and inhibition of P4501A expression, continuous waterborne exposures were performed along with realistic concentrations of the P4501A inducer, BaP. The results of this research project add to the understanding of the regulation of hepatic P4501A gene expression in fish following waterborne exposure to xenobiotics by: (1) determining the concentration and time-dependent threshold values for induction of P4501A mRNA in gill and hepatic tissue following exposure to BaP; and (2) determining the concentration- and time-dependent effects of the inhibitor propiconazole on hepatic P4501A expression following exposure to propiconazole alone, or in a combined exposure to propiconazole and BaP.

Supplemental Keywords:

fellowship, levels, P4501A mRNA, BaP, propiconazole, biomarker determination, toxicity, induction, inhibition, P450 expression. , Scientific Discipline, Health, Risk Assessments, Health Risk Assessment, Biochemistry, Environmental Chemistry, bioavailability, xenobiotics, toxicity, exposure dose, P450 gene expression, waterborne disease, fish species

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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