RNA-protein correlation of liver toxicity markers in HepaRG cells
The liver is a main target organ for the toxicity of many different compounds. While in general, testing is still routinely used for assessing the hepatotoxic potential of test chemicals, the use of models offers advantages with regard to throughput, consumption of resources, and animal welfare aspe...
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Published in | EXCLI journal Vol. 19; pp. 135 - 153 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
Leibniz Research Centre for Working Environment and Human Factors
01.01.2020
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Abstract | The liver is a main target organ for the toxicity of many different compounds. While in general,
testing is still routinely used for assessing the hepatotoxic potential of test chemicals, the use of
models offers advantages with regard to throughput, consumption of resources, and animal welfare aspects. Using the human hepatoma cell line HepaRG, we performed a comparative evaluation of a panel of hepatotoxicity marker mRNAs and proteins after exposure of the cells to 30 different pesticidal active compounds comprising herbizides, fungicides, insecticides, and others. The panel of hepatotoxicity markers included nuclear receptor target genes, key players of fatty acid and bile acid metabolism-related pathways, as well as recently identified biomarkers of drug-induced liver injury. Moreover, marker genes and proteins were identified, for example, S100P, ANXA10, CYP1A1, and CYP7A1. These markers respond with high sensitivity to stimulation with chemically diverse test compounds already at non-cytotoxic concentrations. The potency of the test compounds, determined as an overall parameter of their ability to deregulate marker expression
, was very similar between the mRNA and protein levels. Thus, this study does not only characterize the response of human liver cells to 30 different pesticides but also demonstrates that hepatotoxicity testing in human HepaRG cells yields well comparable results at the mRNA and protein levels. Furthermore, robust hepatotoxicity marker genes and proteins were identified in HepaRG cells. |
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AbstractList | The liver is a main target organ for the toxicity of many different compounds. While in general,
testing is still routinely used for assessing the hepatotoxic potential of test chemicals, the use of
models offers advantages with regard to throughput, consumption of resources, and animal welfare aspects. Using the human hepatoma cell line HepaRG, we performed a comparative evaluation of a panel of hepatotoxicity marker mRNAs and proteins after exposure of the cells to 30 different pesticidal active compounds comprising herbizides, fungicides, insecticides, and others. The panel of hepatotoxicity markers included nuclear receptor target genes, key players of fatty acid and bile acid metabolism-related pathways, as well as recently identified biomarkers of drug-induced liver injury. Moreover, marker genes and proteins were identified, for example, S100P, ANXA10, CYP1A1, and CYP7A1. These markers respond with high sensitivity to stimulation with chemically diverse test compounds already at non-cytotoxic concentrations. The potency of the test compounds, determined as an overall parameter of their ability to deregulate marker expression
, was very similar between the mRNA and protein levels. Thus, this study does not only characterize the response of human liver cells to 30 different pesticides but also demonstrates that hepatotoxicity testing in human HepaRG cells yields well comparable results at the mRNA and protein levels. Furthermore, robust hepatotoxicity marker genes and proteins were identified in HepaRG cells. The liver is a main target organ for the toxicity of many different compounds. While in general, in vivo testing is still routinely used for assessing the hepatotoxic potential of test chemicals, the use of in vitro models offers advantages with regard to throughput, consumption of resources, and animal welfare aspects. Using the human hepatoma cell line HepaRG, we performed a comparative evaluation of a panel of hepatotoxicity marker mRNAs and proteins after exposure of the cells to 30 different pesticidal active compounds comprising herbizides, fungicides, insecticides, and others. The panel of hepatotoxicity markers included nuclear receptor target genes, key players of fatty acid and bile acid metabolism-related pathways, as well as recently identified biomarkers of drug-induced liver injury. Moreover, marker genes and proteins were identified, for example, S100P, ANXA10, CYP1A1, and CYP7A1. These markers respond with high sensitivity to stimulation with chemically diverse test compounds already at non-cytotoxic concentrations. The potency of the test compounds, determined as an overall parameter of their ability to deregulate marker expression in vitro , was very similar between the mRNA and protein levels. Thus, this study does not only characterize the response of human liver cells to 30 different pesticides but also demonstrates that hepatotoxicity testing in human HepaRG cells yields well comparable results at the mRNA and protein levels. Furthermore, robust hepatotoxicity marker genes and proteins were identified in HepaRG cells. |
Author | Planatscher, Hannes Poetz, Oliver Lichtenstein, Dajana Schmidt, Felix F Albaum, Stefan P Braeuning, Albert Mentz, Almut Kalinowski, Jörn Joos, Thomas O |
AuthorAffiliation | 2 Center for Biotechnology (CeBiTec), Universität Bielefeld, Bielefeld, Germany 1 German Federal Institute for Risk Assessment, Dept. Food Safety, Berlin, Germany 4 NMI Natural and Medical Sciences Institute at the University of Tübingen, Tübingen,Germany 3 Signatope GmbH, Reutlingen, Germany |
AuthorAffiliation_xml | – name: 4 NMI Natural and Medical Sciences Institute at the University of Tübingen, Tübingen,Germany – name: 1 German Federal Institute for Risk Assessment, Dept. Food Safety, Berlin, Germany – name: 3 Signatope GmbH, Reutlingen, Germany – name: 2 Center for Biotechnology (CeBiTec), Universität Bielefeld, Bielefeld, Germany |
Author_xml | – sequence: 1 givenname: Albert surname: Braeuning fullname: Braeuning, Albert organization: German Federal Institute for Risk Assessment, Dept. Food Safety, Berlin, Germany – sequence: 2 givenname: Almut surname: Mentz fullname: Mentz, Almut organization: Center for Biotechnology (CeBiTec), Universität Bielefeld, Bielefeld, Germany – sequence: 3 givenname: Felix F surname: Schmidt fullname: Schmidt, Felix F organization: Signatope GmbH, Reutlingen, Germany – sequence: 4 givenname: Stefan P surname: Albaum fullname: Albaum, Stefan P organization: Center for Biotechnology (CeBiTec), Universität Bielefeld, Bielefeld, Germany – sequence: 5 givenname: Hannes surname: Planatscher fullname: Planatscher, Hannes organization: Signatope GmbH, Reutlingen, Germany – sequence: 6 givenname: Jörn surname: Kalinowski fullname: Kalinowski, Jörn organization: Center for Biotechnology (CeBiTec), Universität Bielefeld, Bielefeld, Germany – sequence: 7 givenname: Thomas O surname: Joos fullname: Joos, Thomas O organization: Signatope GmbH, Reutlingen, Germany – sequence: 8 givenname: Oliver surname: Poetz fullname: Poetz, Oliver organization: Signatope GmbH, Reutlingen, Germany – sequence: 9 givenname: Dajana surname: Lichtenstein fullname: Lichtenstein, Dajana organization: German Federal Institute for Risk Assessment, Dept. Food Safety, Berlin, Germany |
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CitedBy_id | crossref_primary_10_3389_ftox_2022_880818 crossref_primary_10_3390_ijms22010372 |
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Copyright | Copyright © 2020 Braeuning et al. Copyright © 2020 Braeuning et al. 2020 |
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Keywords | liver toxicity omics hepatocytes in vitro testing relative potency factors |
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Snippet | The liver is a main target organ for the toxicity of many different compounds. While in general,
testing is still routinely used for assessing the hepatotoxic... The liver is a main target organ for the toxicity of many different compounds. While in general, in vivo testing is still routinely used for assessing the... |
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Title | RNA-protein correlation of liver toxicity markers in HepaRG cells |
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