Review and meta‐analysis of gene expression biomarkers predictive of chemical‐induced genotoxicity in vivo

Environmental and Molecular Mutagenesis, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Abstract There is growing recognition across broad sectors of the toxicology community that gene expression biomarkers have potential to identify genotoxic and nongenotoxic carcinogens through a weight‐of‐evidence approach, providing opportunities reduce reliance on 2‐year bioassay carcinogens. In August 2022, workshop within International Workshops Genotoxicity Testing (IWGT) was held critically review current methods genotoxicants using various ‘omics profiling methods. Here, we describe findings subgroup focused state science regarding use chemicals act as in vivo. A total 1341 papers were screened those most relevant. While six published with characterized accuracy initially examined, four not considered further, because they had been tested for classification additional sets or other transcript platforms. Two independently derived used conjunction standard computational techniques can vivo (rat liver both rat mouse liver) different The predictive accuracies ≥92%. These be integrated test strategies short‐term rodent exposures cause cancer.

Язык: Английский

Review of Transcriptomic Biomarkers That Predict In Vitro Genotoxicity in Human Cell Lines

Environmental and Molecular Mutagenesis, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

ABSTRACT The current genotoxicity testing paradigm provides little mechanistic information, has poor specificity in predicting carcinogenicity humans, and is not suited to assessing a large number of chemicals. Genomic technologies enable the characterization genome‐wide transcriptional changes response chemical treatments that can inform mechanisms or modes action. These provided an impetus develop transcriptomic biomarkers could transform hazard assessment for drugs, cosmetics, environmental industrial In August 2022, International Workshops on Genotoxicity Testing (IWGT) held workshop critically review progress development application testing. Here, we describe findings this workshop's subgroup conducted systematized analysis vitro evaluating genotoxicity. Although there multitude published reports exploring transcriptomics genetic toxicology, working group identified only five biomarker candidates, which three (GENOMARK, TGx‐DDI, MU2012) were independently developed with sufficiently defined context use, validation data, supporting case studies warranted inclusion review. these different classes chemicals (TGx‐DDI pharmaceuticals, GENOMARK MU2012 medical chemicals), they all address same shortfall standard battery, is, lack by genotoxicity‐induced stress at level. review, discuss biomarkers, including challenges toward achieving regulatory acceptance.

Язык: Английский