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Consensus findings of an International Workshops on Genotoxicity Testing Workshop on using Transcriptomic biomarkers to predict genotoxicity
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  • Roland Froetschl,
  • Christopher Corton,
  • Heng-Hong Li,
  • Jiri Aubrecht,
  • Scott Auerbach,
  • Florian Caiment,
  • Tatyana Doktorova,
  • Yurika Fujita,
  • Danyel Jennen,
  • Naoki Koyama,
  • Matthew Meier,
  • Roman Mezencev,
  • Les Recio,
  • Takayoshi Suzuki,
  • Carole Yauk
Roland Froetschl
BfArM Bundesinsitut für Arzneimittel und Medizinprodukte (Federal Institute for Drug and Medical Devices)

Corresponding Author:[email protected]

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Christopher Corton
US-EPA
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Heng-Hong Li
Georgetown University Medical Center
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Jiri Aubrecht
Georgetown University Medical Center
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Scott Auerbach
National Institute of Environmental Health Sciences
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Florian Caiment
Maastricht University Faculty of Health Medicine and Life Sciences
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Tatyana Doktorova
F Hoffmann-La Roche Ltd
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Yurika Fujita
Osaka University
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Danyel Jennen
Maastricht University
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Naoki Koyama
Chugai Pharmaceutical Co Ltd
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Matthew Meier
Health Canada
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Roman Mezencev
US Environmental Protection Agency Office of Research and Development
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Les Recio
ScitoVation
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Takayoshi Suzuki
National Institute of Health Sciences
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Carole Yauk
University of Ottawa
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Abstract

Gene expression biomarkers have the potential to identify genotoxic and nongenotoxic carcinogens, providing opportunities for integrated testing and reducing animal use. In August 2022, an International Workshops on Genotoxicity Testing (IWGT) workshop was held to critically review current methods to identify genotoxicants using transcriptomic profiling. Here, we summarize the workgroup’s findings on the state of the science regarding the use of transcriptomic biomarkers to identify genotoxic chemicals in vitro and in vivo. A total of 1341 papers were examined to identify the biomarkers that show the most promise for identifying genotoxicants. This revealed two independently derived in vivo biomarkers and three in vitro biomarkers that, when used in conjunction with standard computational techniques, can identify genotoxic chemicals in vivo (rat or mouse liver) or in human cells in culture using different gene expression profiling platforms, with predictive accuracies of ≥ 92%. These biomarkers have been validated to differing degrees, but typically show high reproducibility across transcriptomic platforms and model systems. They offer several advantages for applications in different contexts of use in genotoxicity testing including: early signal detection, moderate to high-throughput screening capacity, adaptability to different cell types and tissues, and insights on mechanistic information on DNA-damage response. Workshop participants agreed on consensus statements to advance the regulatory adoption of transcriptomic biomarkers for genotoxicity. The participants agreed that transcriptomic biomarkers have the potential to be used in conjunction with other biomarkers in integrated test strategies in vitro and using short-term rodent exposures to identify genotoxic and nongenotoxic chemicals that may……………….
17 Sep 2024Submitted to Environmental and Molecular Mutagenesis
18 Sep 2024Submission Checks Completed
18 Sep 2024Assigned to Editor
18 Sep 2024Review(s) Completed, Editorial Evaluation Pending
20 Sep 2024Reviewer(s) Assigned