title: Human keratinocyte radiosensitivity is linked to redox modulation.
abstract: BACKGROUND
  Ionising radiation-induced reactive oxygen species (ROS) overproduction induces keratinocyte alterations and constitutes one of the most common effects after therapeutic gamma-irradiation. ROS production is controlled by a complex enzymatic system.
  
  
  OBJECTIVE
  The aim of our study is to analyse the role of radiation-induced oxidative stress in keratinocytes death by apoptosis. We hypothesized that keratinocyte capacity to hamper radiation-induced ROS generation may control their radiosensitivity.
  
  
  METHODS
  For this purpose, an original human skin explant model was developed and two types of human epidermal cells were used: primary keratinocytes NHEK and spontaneous non-tumourigenic cell line HaCaT.
  
  
  RESULTS
  cDNA-arrays analysis was performed 24h after a 20Gy gamma-radiation and revealed down-regulation of genes involved in oxidative stress control and the apoptosis process. This was confirmed by alterations in catalase, GPx and SOD enzymatic activities. This redox modulation was concomitant to the down-regulation of anti-apoptotic genes and up-regulation of some pro-apoptotic genes (caspase 10, ubiquitin C). Interestingly TUNEL labelling revealed an increase in the number of apoptotic cells. We also demonstrated a differential inducibility of the cell antioxidant network in two keratinocyte lines, which results in a differential cellular level of ROS, explaining their different radiosensitivities.
  
  
  CONCLUSIONS
  Keratinocytes apoptosis is partly dependent on ROS production after exposure to gamma-rays. In addition, the differential radiosensitivity of keratinocytes is linked to different oxidative stress responses.
authors.affiliation: Institut de Radioprotection et de Sûreté Nucléaire IRSN, Service de Radiobiologie d'Epidémiologie, Direction de la Radioprotection de l'Homme, Laboratoire de RadioPathologie, IRSN, B.P. no. 17, F-92262 Fontenay-aux-Roses Cedex, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Isoir
authors.forename: Valérie
authors.initials: V
authors.lastname: Buard
authors.forename: Philippe
authors.initials: P
authors.lastname: Gasser
authors.forename: Philippe
authors.initials: P
authors.lastname: Voisin
authors.forename: Elian
authors.initials: E
authors.lastname: Lati
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000528:radiation effects*; D002374:Catalase / Q000378:metabolism; D002461:Cell Line, Transformed; D000078404:Epidermal Cells; D005260:Female; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology* / Q000528:radiation effects*; D010084:Oxidation-Reduction / Q000528:radiation effects; D018384:Oxidative Stress / Q000528:radiation effects*; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase