Authors: Hammer, Helen
Schmidt, Flavia
Heise, Tanja
Knebel, Constanze
Dabrowski, Alexander
Planatscher, Hannes
Kneuer, Carsten
Marx-Stoelting, Philip
Pötz, Oliver
Title: Induction and repression effects on CYP and transporter protein abundance by azole mixture uptake in rat liver
Language (ISO): en
Abstract: Detection of mixture effects is a major challenge in current experimental and regulatory toxicology. Robust markers are needed that are easy to quantify and responsive to chemical stressors in a broad dose range. Several hepatic enzymes and proteins related to drug metabolism like cytochrome-P-450 (CYP) enzymes and transporters have been shown to be responsive to pesticide active substances in a broad dose range and are therefore good candidates to be used as markers for mixture toxicity. Even though they can be well quantified at the mRNA level, quantification on the protein level is challenging because most of these proteins are membrane bound. Here we report the development of mass spectrometry-based assays using triple-x-proteomics (TXP) antibodies in combination with targeted selected ion monitoring (tSIM) to quantify changes of protein levels due to exposure to mixtures of pesticide active substances. Our results indicate that changes on the protein level of CYP1A1, ABCB2, ABCC3 are in line with observations on the mRNA and enzyme activity level and are indicative of mixture effects. Therefore, the tests are promising to reveal effects by chemical mixture effects in toxicological studies in rats.
Subject Headings: ABC transporter
Azole fungicides
Cytochrome P450
Immunoaffinity-based mass spectrometry
Liver toxicity
Pesticide mixtures
SLC transporter
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Issue Date: 2020-06-26
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Provenance: IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund
Citation: Hammer, H., Schmidt, F., Heise, T., Knebel, C., Dabrowski, A., Planatscher, H., Kneuer, C., Marx-Stoelting, P., & Pötz, O. (2020). Induction and repression effects on CYP and transporter protein abundance by azole mixture uptake in rat liver. EXCLI Journal, 19, 904-916.
Appears in Collections:Original Articles 2020

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