SaferWorldbyDesign Webinar: The GENOMARK biomarker in human HepaRG™ cells: a new approach methodology for genotoxicity assessment

To modernize genotoxicity assessment, new strategies for testing and assessment are needed, including the integration of New Approach Methodologies (NAMs). We previously developed GENOMARK, a transcriptomics-based biomarker consisting of 84 genes to identify genotoxic substances in metabolically competent human HepaRG™ cells. In this webinar, the development of GENOMARK and the application of two new prediction models to classify chemicals for genotoxicity will be discussed. We will also demonstrate how GENOMARK gene expression data can be used in a more quantitative way, i.e. for potency ranking of genotoxic chemicals. To this extent, a case study where we applied the benchmark dose (BMD) modelling approach on GENOMARK data generated by qPCR from two known in vivo genotoxic chemicals, aflatoxin B1 (AFB1) and ethyl methanesulfonate (EMS), will be presented. Additionally, we will show the applicability of GENOMARK to gene expression data collected with higher-throughput platforms, such as RNA-Seq and TempO-Seq, which are more efficient than using the PCR array. These approaches can generate a large amount of gene expression data in a shorter timeframe, facilitating the combination of GENOMARK with other transcriptomics-based biomarkers such as TGx-DDI. Overall, the results obtained so far support a future role of GENOMARK in integrated testing strategies for genotoxicity assessment.

Presenter: Anouck Thienpont (Vrije Universiteit Brussel)

Anouck Thienpont started her Ph.D. in 2019 in the Department of in vitro dermato-cosmetology and toxicology at the Vrije Universiteit Brussel (VUB) in collaboration with Sciensano. She has a background in pharmaceutical sciences and has a personal interest in the safety of cosmetic products. Her Ph.D. focuses on the integration and practical use of toxicogenomics-based biomarkers in a 21st-century risk assessment approach for genotoxicity with a focus on the GENOMARK biomarker.

A. Thienpont 1, S. Verhulst 2, L.A. van Grunsven 2, V. Rogiers 1*, T. Vanhaecke 1* and B. Mertens 3*

1Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium

2Liver Cell Biology research group, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium

3Department of Chemical and Physical Health Risks, Sciensano, Juliette Wytsmanstraat 14, 1050 Brussels, Belgium