Application of the ethoxyresorufin-O-deethylase (EROD) assay to mixtures of halogenated aromatic compounds

Environmental Toxicology
J R PetrulisN J Bunce

Abstract

The ethoxyresorufin-O-deethylase (EROD) assay monitors the induction of the xenobiotic-metabolizing enzyme cytochrome P-450 (CYP) 1A1 and is a widely used biomarker for exposure of wildlife to substances that bind the aryl hydrocarbon (Ah) receptor. In this work the induction of EROD activity by single compounds and binary mixtures in primary rat hepatocytes was compared with the predictions of a kinetic model involving mixtures of inducers. The inducing agents were also examined for their ability to activate the Ah receptor to its DNA-binding form and for their ability to act as competitive inhibitors for CYP 1A1. Xenobiotics that failed to activate the Ah receptor did not induce EROD activity. Competitive inhibition for CYP 1A1 between the xenobiotic and 7-ethoxyresorufin caused EROD activity to fall at high xenobiotic concentrations. Competition for a limited number of Ah receptor sites depressed the EROD activity of a strong inducer such as 2,3,7,8-tetrachlorodibenzo-p-dioxin at high concentrations of a weak inducer. Application of the kinetic model to the example of a mixture of low concentrations of dibenzo-p-dioxins and much higher concentrations of polychlorinated biphenyls indicated that EROD assays often seriously und...Continue Reading

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Citations

Jul 28, 2011·Environmental Science and Pollution Research International·Bernhard WetterauerHenner Hollert
Jun 24, 2008·Journal of Toxicology and Environmental Health. Part a·Erica D BruceThomas J McDonald
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Mar 13, 2013·Toxicology Mechanisms and Methods·Bo-Jeng WangHsinyu Lee
Dec 3, 2014·The Journal of Steroid Biochemistry and Molecular Biology·Ryeo-Eun GoKyung-Chul Choi
Sep 30, 2003·Toxicological Sciences : an Official Journal of the Society of Toxicology·Guosheng Chen, Nigel J Bunce
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Aug 19, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Amaia Ereño ArtabeAlejandro Barranco

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