Validation of the γH2AX biomarker for genotoxicity assessment: a review
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The H2AX histone protein is rapidly phosphorylated at the serine-139 position (γH2AX) in response to a broad range of DNA lesions. γH2AX induction is one of the earliest events in the DNA damage response (DDR) and plays a central role in sensing and repairing DNA damage. Since its discovery, measuring γH2AX formation using numerous methods in in vitro and in vivo experiments has been an attractive endpoint for the detection of genotoxic agents. Our review focuses on validation studies performed using this biomarker to detect the genotoxicity of model chemicals using different methods. To date, nearly two hundred genotoxic and carcinogenic model chemicals have been shown to induce in vitro γH2AX in different cell lines by numerous laboratories. Based on 27 published reports comprising 329 tested chemicals, we compared the performance of the γH2AX assay with other genotoxic endpoints (Ames assay, micronucleus, HPRT and comet) regularly used for in vitro genotoxicity assessment. Notably, the γH2AX assay performs well (91% predictivity) and efficiently differentiates aneugenic and clastogenic compounds when coupled with the pH3 biomarker. Currently, no formal guidelines have been approved for the γH2AX assay for regular genotoxicity studies, but we suggest the γH2AX biomarker could be used as a new standard genotoxicity assay and discuss its future role in genotoxicity risk assessment.
KeywordsγH2AX pH3 Genotoxicity DNA damage Micronucleus Biomarker
We apologize for any literature that we were unable to cite due to space limitations. B. Kopp was supported by a doctoral fellowship from INRA and ANSES.
All the authors contributed to writing the manuscript.
Compliance with ethical standards
Conflict of interest
MA and LK are co-founders of Preditox SAS. LK is CEO of Preditox. MA serves as consultant to Preditox SAS.
- Chevereau M, Glatt H, Zalko D, Cravedi J-P, Audebert M (2017) Role of human sulfotransferase 1A1 and N-acetyltransferase 2 in the metabolic activation of 16 heterocyclic amines and related heterocyclics to genotoxicants in recombinant V79 cells. Arch Toxicol 91(9):3175–3184CrossRefPubMedGoogle Scholar
- Kuo LJ, Yang L-X (2008) γH2AX—a novel biomarker for DNA double-strand breaks. Vivo 22(3):305–309Google Scholar
- OECD (2014) OECD test guidelines for testing of chemicals: introduction to the OECD guidelines on genetic toxicology. https://www.oecd.org/env/ehs/testing/oecdguidelinesforthetestingofchemicals.htm