title: The effects of selenium and the GPx-1 selenoprotein on the phosphorylation of H2AX.
abstract: BACKGROUND
  Significant data supports the health benefits of selenium although supplementation trials have yielded mixed results. GPx-1, whose levels are responsive to selenium availability, is implicated in cancer etiology by human genetic data. Selenium's ability to alter the phosphorylation of the H2AX, a histone protein that functions in the reduction of DNA damage by recruiting repair proteins to the damage site, following exposure to ionizing radiation and bleomycin was investigated.
  
  
  METHODS
  Human cell lines that were either exposed to selenium or were transfected with a GPx-1 expression construct were exposed to ionizing radiation or bleomycin. Phosphorylation of histone H2AX was quantified by flow cytometry and survival by the MTT assay. Phosphorylation of the Chk1 and Chk2 checkpoint proteins was quantified by western blotting.
  
  
  RESULTS
  In colon-derived cells, selenium increases GPx-1 and attenuated H2AX phosphorylation following genotoxic exposures while the viability of these cells was unaffected. MCF-7 cells and transfectants that express high GPx-1 levels were exposed to ionizing radiation and bleomycin, and H2AX phosphorylation and cell viability were assessed. GPx-1 increased H2AX phosphorylation and viability following the induction of DNA damage while enhancing the levels of activated Chk1 and Chk2.
  
  
  CONCLUSIONS
  Exposure of mammalian cells to selenium can alter the DNA damage response and do so by mechanisms that are dependent and independent of its effect on GPx-1.
  
  
  CONCLUSIONS
  Selenium and GPx-1 may stimulate the repair of genotoxic DNA damage and this may account for some of the benefits attributed to selenium intake and elevated GPx-1 activity.
authors.affiliation: Department of Pathology, University of Illinois, Chicago, IL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jerome-Morais
authors.forename: S
authors.initials: S
authors.lastname: Bera
authors.forename: W
authors.initials: W
authors.lastname: Rachidi
authors.forename: P H
authors.initials: PH
authors.lastname: Gann
authors.forename: A M
authors.initials: AM
authors.lastname: Diamond
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D012643:Selenium / Q000378:metabolism*; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000903:Antibiotics, Antineoplastic; C468783:H2AX protein, human; D006657:Histones; D051140:Selenoproteins; D001761:Bleomycin; D005979:Glutathione Peroxidase; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human