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Archives of Toxicology

, Volume 93, Issue 8, pp 2103–2114 | Cite as

Validation of the γH2AX biomarker for genotoxicity assessment: a review

  • B. Kopp
  • L. Khoury
  • Marc AudebertEmail author
Review Article
  • 477 Downloads

Abstract

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.

Keywords

γH2AX pH3 Genotoxicity DNA damage Micronucleus Biomarker 

Notes

Acknowledgements

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.

Author contributions

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.

Supplementary material

204_2019_2511_MOESM1_ESM.xlsx (99 kb)
Supplementary material 1 (XLSX 98 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Toxalim, Université de Toulouse, INRA, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul SabatierToulouseFrance
  2. 2.ANSES, French Agency for Food, Environmental and Occupational Health and Safety, Toxicology of Contaminants UnitFougèresFrance
  3. 3.PrediToxToulouseFrance
  4. 4.INRA-UMR1331Toulouse Cedex 3France

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