Consensus findings of an International Workshops on Genotoxicity Testing
Workshop on using Transcriptomic biomarkers to predict genotoxicity
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……………….