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Validation of the γH2AX biomarker for genotoxicity assessment: a review

Abstract : The H2AX histone protein is rapidly phosphorylated at the serine-139 position (gammaH2AX) in response to a broad range of DNA lesions. gammaH2AX 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 gammaH2AX 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 gammaH2AX in different cell lines by numerous laboratories. Based on 27 published reports comprising 329 tested chemicals, we compared the performance of the gammaH2AX assay with other genotoxic endpoints (Ames assay, micronucleus, HPRT and comet) regularly used for in vitro genotoxicity assessment. Notably, the gammaH2AX 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 gammaH2AX assay for regular genotoxicity studies, but we suggest the gammaH2AX biomarker could be used as a new standard genotoxicity assay and discuss its future role in genotoxicity risk assessment.
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https://hal-anses.archives-ouvertes.fr/anses-02349053
Contributor : Emmanuelle Chiffoleau <>
Submitted on : Tuesday, November 5, 2019 - 3:14:51 PM
Last modification on : Tuesday, August 11, 2020 - 10:08:02 PM

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Benjamin Kopp, Laure Khoury, Marc Audebert. Validation of the γH2AX biomarker for genotoxicity assessment: a review. Archives of Toxicology, Springer Verlag, 2019, 93 (8), pp.2103-2114. ⟨10.1007/s00204-019-02511-9⟩. ⟨anses-02349053⟩

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