title: GammaH2AX, an accurate marker that analyzes UV genotoxic effects on human keratinocytes and on human skin.
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.
authors.affiliation: Laboratoire de Dermatologie Moléculaire, Institut Universitaire de Recherche Clinique, Montpellier, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Barnes
authors.forename: Marc
authors.initials: M
authors.lastname: Dumas
authors.forename: Mylène
authors.initials: M
authors.lastname: Juan
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Noblesse
authors.forename: Anne
authors.initials: A
authors.lastname: Tesniere
authors.forename: Sylvianne
authors.initials: S
authors.lastname: Schnebert
authors.forename: Bernard
authors.initials: B
authors.lastname: Guillot
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Molès
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D006657:Histones / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D010766:Phosphorylation; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D015415:Biomarkers; C468783:H2AX protein, human; D006657:Histones; D004247:DNA