GammaH2AX, an accurate marker that analyzes UV genotoxic effects on human keratinocytes and on human skin
The phosphorylated form of histone H2AX, gammaH2AX, is a component of the DNA repair system. Most studies have focused on the role of gammaH2AX during cell transformation and human cancer, but little is known about its role in keratinocytes and the skin during UV irradiation. We analyzed the respons...
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Veröffentlicht in: | Photochemistry and photobiology 2010-07, Vol.86 (4), p.933-941 |
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creator | Barnes, Laurent Dumas, Marc Juan, Mylène Noblesse, Emmanuelle Tesniere, Anne Schnebert, Sylvianne Guillot, Bernard Molès, Jean-Pierre |
description | The phosphorylated form of histone H2AX, gammaH2AX, is a component of the DNA repair system. Most studies have focused on the role of gammaH2AX during cell transformation and human cancer, but little is known about its role in keratinocytes and the skin during UV irradiation. We analyzed the response to UV irradiation focusing on the phosphorylation of histone H2AX both in vitro, in keratinocyte cultures and in artificial epidermis, and then in vivo, in human skin. Acute UVB irradiation of human keratinocytes increased the phosphorylation of H2AX in a dose-dependent manner; two types of gammaH2AX response were observed either in vitro or in vivo. After a low nonapoptotic UVB irradiation, cells contained phosphorylated H2AX and arrested their cell cycle to repair the DNA damages. For a stronger and proapoptotic UVB irradiation, keratinocytes dramatically increased the phosphorylation of H2AX and committed apoptosis. Our results indicate that gammaH2AX constitutes a highly sensitive marker relevant for studying subapoptotic doses as well as proapoptotic doses of UVB in human skin. |
doi_str_mv | 10.1111/j.1751-1097.2010.00744.x |
format | Article |
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Most studies have focused on the role of gammaH2AX during cell transformation and human cancer, but little is known about its role in keratinocytes and the skin during UV irradiation. We analyzed the response to UV irradiation focusing on the phosphorylation of histone H2AX both in vitro, in keratinocyte cultures and in artificial epidermis, and then in vivo, in human skin. Acute UVB irradiation of human keratinocytes increased the phosphorylation of H2AX in a dose-dependent manner; two types of gammaH2AX response were observed either in vitro or in vivo. After a low nonapoptotic UVB irradiation, cells contained phosphorylated H2AX and arrested their cell cycle to repair the DNA damages. For a stronger and proapoptotic UVB irradiation, keratinocytes dramatically increased the phosphorylation of H2AX and committed apoptosis. Our results indicate that gammaH2AX constitutes a highly sensitive marker relevant for studying subapoptotic doses as well as proapoptotic doses of UVB in human skin.</description><subject>Apoptosis - radiation effects</subject><subject>Biomarkers - analysis</subject><subject>Biomarkers - metabolism</subject><subject>Cells, Cultured</subject><subject>DNA - genetics</subject><subject>DNA - radiation effects</subject><subject>DNA Damage</subject><subject>DNA Repair</subject><subject>Dose-Response Relationship, Radiation</subject><subject>Histones - analysis</subject><subject>Histones - genetics</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Keratinocytes - metabolism</subject><subject>Keratinocytes - radiation effects</subject><subject>Phosphorylation</subject><subject>Skin - metabolism</subject><subject>Skin - radiation effects</subject><subject>Ultraviolet Rays</subject><issn>1751-1097</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkEtLA0EQhAdBTIz-BZmbF3ed12YzxxA0EQJeonhbemZ7zCb7iDuzkPjrHfDVl4aqrxuqCKGcpTzO_S7lecYTznSeChZVxnKl0uMZGf8ZI3Lp_Y4xrnTOL8hIMKVFNlVjUi2haWAl5m93FFoK1g49BKQN9HvsadhCiDrUp0_09OWVvmPbhe5YWYrOoQ2edi3dDk28jTyEqu3sKUQW2vLf8vuqvSLnDmqP1z97QjaPD5vFKlk_L58W83VyyDKVGOGkcQassghouUKdMzMthRBZaXipOQIzqGbaZZLn2nEFJQqhSzblwmk5Ibffbw999zGgD0VTeYt1DS12gy9yqWJJMykjefNDDqbBsjj0VUx9Kn7LkV_iN2ds</recordid><startdate>201007</startdate><enddate>201007</enddate><creator>Barnes, Laurent</creator><creator>Dumas, Marc</creator><creator>Juan, Mylène</creator><creator>Noblesse, Emmanuelle</creator><creator>Tesniere, Anne</creator><creator>Schnebert, Sylvianne</creator><creator>Guillot, Bernard</creator><creator>Molès, Jean-Pierre</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201007</creationdate><title>GammaH2AX, an accurate marker that analyzes UV genotoxic effects on human keratinocytes and on human skin</title><author>Barnes, Laurent ; Dumas, Marc ; Juan, Mylène ; Noblesse, Emmanuelle ; Tesniere, Anne ; Schnebert, Sylvianne ; Guillot, Bernard ; Molès, Jean-Pierre</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p554-b2f3bfbac4ceaec14e970b6d2225db1d91ea0be489f53179f14ade229d0612f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Apoptosis - radiation effects</topic><topic>Biomarkers - analysis</topic><topic>Biomarkers - metabolism</topic><topic>Cells, Cultured</topic><topic>DNA - genetics</topic><topic>DNA - radiation effects</topic><topic>DNA Damage</topic><topic>DNA Repair</topic><topic>Dose-Response Relationship, Radiation</topic><topic>Histones - analysis</topic><topic>Histones - genetics</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Keratinocytes - metabolism</topic><topic>Keratinocytes - radiation effects</topic><topic>Phosphorylation</topic><topic>Skin - metabolism</topic><topic>Skin - radiation effects</topic><topic>Ultraviolet Rays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barnes, Laurent</creatorcontrib><creatorcontrib>Dumas, Marc</creatorcontrib><creatorcontrib>Juan, Mylène</creatorcontrib><creatorcontrib>Noblesse, Emmanuelle</creatorcontrib><creatorcontrib>Tesniere, Anne</creatorcontrib><creatorcontrib>Schnebert, Sylvianne</creatorcontrib><creatorcontrib>Guillot, Bernard</creatorcontrib><creatorcontrib>Molès, Jean-Pierre</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Photochemistry and photobiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barnes, Laurent</au><au>Dumas, Marc</au><au>Juan, Mylène</au><au>Noblesse, Emmanuelle</au><au>Tesniere, Anne</au><au>Schnebert, Sylvianne</au><au>Guillot, Bernard</au><au>Molès, Jean-Pierre</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GammaH2AX, an accurate marker that analyzes UV genotoxic effects on human keratinocytes and on human skin</atitle><jtitle>Photochemistry and photobiology</jtitle><addtitle>Photochem Photobiol</addtitle><date>2010-07</date><risdate>2010</risdate><volume>86</volume><issue>4</issue><spage>933</spage><epage>941</epage><pages>933-941</pages><eissn>1751-1097</eissn><abstract>The phosphorylated form of histone H2AX, gammaH2AX, is a component of the DNA repair system. Most studies have focused on the role of gammaH2AX during cell transformation and human cancer, but little is known about its role in keratinocytes and the skin during UV irradiation. We analyzed the response to UV irradiation focusing on the phosphorylation of histone H2AX both in vitro, in keratinocyte cultures and in artificial epidermis, and then in vivo, in human skin. Acute UVB irradiation of human keratinocytes increased the phosphorylation of H2AX in a dose-dependent manner; two types of gammaH2AX response were observed either in vitro or in vivo. After a low nonapoptotic UVB irradiation, cells contained phosphorylated H2AX and arrested their cell cycle to repair the DNA damages. For a stronger and proapoptotic UVB irradiation, keratinocytes dramatically increased the phosphorylation of H2AX and committed apoptosis. Our results indicate that gammaH2AX constitutes a highly sensitive marker relevant for studying subapoptotic doses as well as proapoptotic doses of UVB in human skin.</abstract><cop>United States</cop><pmid>20492564</pmid><doi>10.1111/j.1751-1097.2010.00744.x</doi><tpages>9</tpages></addata></record> |
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subjects | Apoptosis - radiation effects Biomarkers - analysis Biomarkers - metabolism Cells, Cultured DNA - genetics DNA - radiation effects DNA Damage DNA Repair Dose-Response Relationship, Radiation Histones - analysis Histones - genetics Histones - metabolism Humans Keratinocytes - metabolism Keratinocytes - radiation effects Phosphorylation Skin - metabolism Skin - radiation effects Ultraviolet Rays |
title | GammaH2AX, an accurate marker that analyzes UV genotoxic effects on human keratinocytes and on human skin |
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