Cargando…
The hen’s egg test for micronucleus induction (HET-MN): validation data set
The classical in vitro genotoxicity test battery is known to be sensitive for indicating genotoxicity. However, a high rate of ‘misleading positives’ was reported when three assays were combined as required by several legislations. Despite the recent optimisations of the standard in vitro tests, two...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071061/ https://www.ncbi.nlm.nih.gov/pubmed/34080017 http://dx.doi.org/10.1093/mutage/geab016 |
_version_ | 1784700768290340864 |
---|---|
author | Reisinger, Kerstin Fieblinger, Dagmar Heppenheimer, Andreas Kreutz, Jürgen Liebsch, Manfred Luch, Andreas Maul, Katrin Poth, Albrecht Strauch, Pamela Dony, Eva Schulz, Markus Wolf, Thorsten Pirow, Ralph |
author_facet | Reisinger, Kerstin Fieblinger, Dagmar Heppenheimer, Andreas Kreutz, Jürgen Liebsch, Manfred Luch, Andreas Maul, Katrin Poth, Albrecht Strauch, Pamela Dony, Eva Schulz, Markus Wolf, Thorsten Pirow, Ralph |
author_sort | Reisinger, Kerstin |
collection | PubMed |
description | The classical in vitro genotoxicity test battery is known to be sensitive for indicating genotoxicity. However, a high rate of ‘misleading positives’ was reported when three assays were combined as required by several legislations. Despite the recent optimisations of the standard in vitro tests, two gaps could hardly be addressed with assays based on 2D monolayer cell cultures: the route of exposure and a relevant intrinsic metabolic capacity to transform pro-mutagens into reactive metabolites. Following these considerations, fertilised chicken eggs have been introduced into genotoxicity testing and were combined with a classical read-out parameter, the micronucleus frequency in circulating erythrocytes, to develop the hen’s egg test for micronucleus induction (HET-MN). As a major advantage, the test mirrors the systemic availability of compounds after oral exposure by reflecting certain steps of Absorption, Distribution, Metabolism, Excretion (ADME) without being considered as an animal experiment. The assay is supposed to add to a toolbox of assays to follow up on positive findings from initial testing with classical in vitro assays. We here report on a validation exercise, in which >30 chemicals were tested double-blinded in three laboratories. The specificity and sensitivity of the HET-MN were calculated to be 98 and 84%, respectively, corresponding to an overall accuracy of 91%. A detailed protocol, which includes a picture atlas detailing the cell and micronuclei analysis, is published in parallel (Maul et al. Validation of the hen’s egg test for micronucleus induction (HET-MN): detailed protocol including scoring atlas, historical control data and statistical analysis). |
format | Online Article Text |
id | pubmed-9071061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-90710612022-05-06 The hen’s egg test for micronucleus induction (HET-MN): validation data set Reisinger, Kerstin Fieblinger, Dagmar Heppenheimer, Andreas Kreutz, Jürgen Liebsch, Manfred Luch, Andreas Maul, Katrin Poth, Albrecht Strauch, Pamela Dony, Eva Schulz, Markus Wolf, Thorsten Pirow, Ralph Mutagenesis Original Manuscripts The classical in vitro genotoxicity test battery is known to be sensitive for indicating genotoxicity. However, a high rate of ‘misleading positives’ was reported when three assays were combined as required by several legislations. Despite the recent optimisations of the standard in vitro tests, two gaps could hardly be addressed with assays based on 2D monolayer cell cultures: the route of exposure and a relevant intrinsic metabolic capacity to transform pro-mutagens into reactive metabolites. Following these considerations, fertilised chicken eggs have been introduced into genotoxicity testing and were combined with a classical read-out parameter, the micronucleus frequency in circulating erythrocytes, to develop the hen’s egg test for micronucleus induction (HET-MN). As a major advantage, the test mirrors the systemic availability of compounds after oral exposure by reflecting certain steps of Absorption, Distribution, Metabolism, Excretion (ADME) without being considered as an animal experiment. The assay is supposed to add to a toolbox of assays to follow up on positive findings from initial testing with classical in vitro assays. We here report on a validation exercise, in which >30 chemicals were tested double-blinded in three laboratories. The specificity and sensitivity of the HET-MN were calculated to be 98 and 84%, respectively, corresponding to an overall accuracy of 91%. A detailed protocol, which includes a picture atlas detailing the cell and micronuclei analysis, is published in parallel (Maul et al. Validation of the hen’s egg test for micronucleus induction (HET-MN): detailed protocol including scoring atlas, historical control data and statistical analysis). Oxford University Press 2021-06-03 /pmc/articles/PMC9071061/ /pubmed/34080017 http://dx.doi.org/10.1093/mutage/geab016 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Manuscripts Reisinger, Kerstin Fieblinger, Dagmar Heppenheimer, Andreas Kreutz, Jürgen Liebsch, Manfred Luch, Andreas Maul, Katrin Poth, Albrecht Strauch, Pamela Dony, Eva Schulz, Markus Wolf, Thorsten Pirow, Ralph The hen’s egg test for micronucleus induction (HET-MN): validation data set |
title | The hen’s egg test for micronucleus induction (HET-MN): validation data set |
title_full | The hen’s egg test for micronucleus induction (HET-MN): validation data set |
title_fullStr | The hen’s egg test for micronucleus induction (HET-MN): validation data set |
title_full_unstemmed | The hen’s egg test for micronucleus induction (HET-MN): validation data set |
title_short | The hen’s egg test for micronucleus induction (HET-MN): validation data set |
title_sort | hen’s egg test for micronucleus induction (het-mn): validation data set |
topic | Original Manuscripts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071061/ https://www.ncbi.nlm.nih.gov/pubmed/34080017 http://dx.doi.org/10.1093/mutage/geab016 |
work_keys_str_mv | AT reisingerkerstin thehenseggtestformicronucleusinductionhetmnvalidationdataset AT fieblingerdagmar thehenseggtestformicronucleusinductionhetmnvalidationdataset AT heppenheimerandreas thehenseggtestformicronucleusinductionhetmnvalidationdataset AT kreutzjurgen thehenseggtestformicronucleusinductionhetmnvalidationdataset AT liebschmanfred thehenseggtestformicronucleusinductionhetmnvalidationdataset AT luchandreas thehenseggtestformicronucleusinductionhetmnvalidationdataset AT maulkatrin thehenseggtestformicronucleusinductionhetmnvalidationdataset AT pothalbrecht thehenseggtestformicronucleusinductionhetmnvalidationdataset AT strauchpamela thehenseggtestformicronucleusinductionhetmnvalidationdataset AT donyeva thehenseggtestformicronucleusinductionhetmnvalidationdataset AT schulzmarkus thehenseggtestformicronucleusinductionhetmnvalidationdataset AT wolfthorsten thehenseggtestformicronucleusinductionhetmnvalidationdataset AT pirowralph thehenseggtestformicronucleusinductionhetmnvalidationdataset AT reisingerkerstin henseggtestformicronucleusinductionhetmnvalidationdataset AT fieblingerdagmar henseggtestformicronucleusinductionhetmnvalidationdataset AT heppenheimerandreas henseggtestformicronucleusinductionhetmnvalidationdataset AT kreutzjurgen henseggtestformicronucleusinductionhetmnvalidationdataset AT liebschmanfred henseggtestformicronucleusinductionhetmnvalidationdataset AT luchandreas henseggtestformicronucleusinductionhetmnvalidationdataset AT maulkatrin henseggtestformicronucleusinductionhetmnvalidationdataset AT pothalbrecht henseggtestformicronucleusinductionhetmnvalidationdataset AT strauchpamela henseggtestformicronucleusinductionhetmnvalidationdataset AT donyeva henseggtestformicronucleusinductionhetmnvalidationdataset AT schulzmarkus henseggtestformicronucleusinductionhetmnvalidationdataset AT wolfthorsten henseggtestformicronucleusinductionhetmnvalidationdataset AT pirowralph henseggtestformicronucleusinductionhetmnvalidationdataset |