Validation of the γH2AX biomarker for genotoxicity assessment: a review
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, measuri...
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| Veröffentlicht in: | Archives of toxicology 2019-08, Vol.93 (8), p.2103-2114 |
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| creator | Kopp, B. Khoury, L. Audebert, Marc |
| description | 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. |
| doi_str_mv | 10.1007/s00204-019-02511-9 |
| format | Article |
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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. 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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.</description><subject>Assaying</subject><subject>Biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Carcinogens</subject><subject>Cell lines</subject><subject>Chemicals</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA damage</subject><subject>Environmental Health</subject><subject>Genotoxic chemicals</subject><subject>Genotoxicity</subject><subject>In vitro methods and tests</subject><subject>In vivo methods and tests</subject><subject>Lesions</subject><subject>Life Sciences</subject><subject>Maintenance</subject><subject>Occupational Medicine/Industrial Medicine</subject><subject>Organic chemistry</subject><subject>Pharmacology/Toxicology</subject><subject>Review Article</subject><subject>Risk assessment</subject><subject>Serine</subject><subject>Toxicology</subject><issn>0340-5761</issn><issn>1432-0738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc9OGzEQxq0KVALtC3BAlrggVUvH9no35hZFbVMpEpeCerO83lnisFmDvQnNc_U9eKY6Xf5IHDjNSPObb77RR8gxg3MGUH6NABzyDJjKgEvGMvWBjFgueAalGO-REYgcMlkW7IAcxrgEYHysxEdyIHZNakdkdm1aV5ve-Y76hvYLpI9_Z3zym1bOr0y4xUAbH-gNdr73f5x1_ZaaGDHGFXb9BTU04Mbhwyey35g24uenekSuvn_7NZ1l88sfP6eTeWZzxvrMAIybWpSmaqQRlSmkLIXgFWusYMrWNSBHXjNEYcbpP9nYoiwrtIWslFRWHJEvg-7CtPouuORxq71xejaZa9MlYxq4yBVIsWGJPhvou-Dv1xh7vXLRYtuaDv06as6lzAupBCT09A269OvQpV92VM4U8DJPFB8oG3yMAZsXDwz0LhU9pKJTKvp_KlqlpZMn6XW1wvpl5TmGBIgBiGnU3WB4vf2O7D9iTZai</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Kopp, B.</creator><creator>Khoury, L.</creator><creator>Audebert, Marc</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><general>Springer Verlag</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T2</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>MBDVC</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-7898-6912</orcidid></search><sort><creationdate>20190801</creationdate><title>Validation of the γH2AX biomarker for genotoxicity assessment: a review</title><author>Kopp, B. ; 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| subjects | Assaying Biomarkers Biomedical and Life Sciences Biomedicine Carcinogens Cell lines Chemicals Deoxyribonucleic acid DNA DNA damage Environmental Health Genotoxic chemicals Genotoxicity In vitro methods and tests In vivo methods and tests Lesions Life Sciences Maintenance Occupational Medicine/Industrial Medicine Organic chemistry Pharmacology/Toxicology Review Article Risk assessment Serine Toxicology |
| title | Validation of the γH2AX biomarker for genotoxicity assessment: a review |
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