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General Signature of Genotoxicity: Evaluation through a meta-analysis of gene expression studies

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  • Overview
Identification of carcinogenic hazard and discrimination between genotoxic and non-genotoxic carcinogens are important components of chemical risk assessment; however, it remains challenging due to the recognized limitations of traditional genotoxicity assays, such as often conflicting results. We have previously derived a General Signature of Genotoxicity (GSG) based on the systematic review of published in vivo transcriptomic studies involving several different tissues and animal species. The GSG consists of genes that tend to display up-regulation following genotoxic challenge that have differing degrees of conservation of response across tissues. In this study, we examined changes in expression of the GSG genes after various genotoxic and non-genotoxic exposures, using the in vitro and in vivo data accessed through the BaseSpace Correlation Engine (Illumina). We demonstrate that individual GSG genes and their combinations display considerable differences in their predictive ability, and we discuss the applicability of the GSG for its use to predict genotoxicity from transcriptomic data. Our results support the potential of the GSG to inform chemical risk assessment. Disclaimer:  The views expressed are those of the authors and do not necessarily represent the views or policies of the US EPA.

Impact/Purpose

Discrimination between genotoxic and non-genotoxic carcinogens is an important component of chemical risk assessment; however, it remains challenging due to recognized limitations of traditional genotoxicity assays. Here we present an evaluation of the General Signature of Genotoxicity (GSG) using in vitro and in vivo transcriptomic data from public repositories. Our evaluation of predictive performance and applicability of the GSG signature will allow more confident use of transcriptomic data to predict genotoxicity and inform human health risk assessment. 

Citation

Mezencev, R. AND S. Auerbach. General Signature of Genotoxicity: Evaluation through a meta-analysis of gene expression studies. 10th Annual Meeting of the ASCCT: "Practical applications of new tools in toxicology", NA, October 12 - 14, 2021.
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Last updated on May 24, 2022
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