title: The importance of bystander effects in radiation therapy in melanoma skin-cancer cells and umbilical-cord stromal stem cells.
abstract: OBJECTIVE
  To examine direct and bystander radiation-induced effects in normal umbilical-cord stromal stem cell (HCSSC) lines and in human cancer cells.
  
  
  METHODS
  The UCSSC lines used in this study were obtained in our laboratory. Two cell lines (UCSSC 35 and UCSSC 37) and two human melanoma skin-cancer cells (A375 and G361) were exposed to ionizing radiation to measure acute radiation-dosage cell-survival curves and radiation-induced bystander cell-death response. Normal cells, although extremely sensitive to ionizing radiation, were resistant to the bystander effect whilst tumor cells were sensitive to irradiated cell-conditioned media, showing a dose-response relationship that became saturated at relatively low doses. We applied a biophysical model to describe bystander cell-death through the binding of a ligand to the cells. This model allowed us to calculate the maximum cell death (χ(max)) produced by the bystander effect together with its association constant (K(By)) in terms of dose equivalence (Gy). The values obtained for K(By) in A375 and G361 cells were 0.23 and 0.29 Gy, respectively.
  
  
  CONCLUSIONS
  Our findings help to understand how anticancer therapy could have an additional decisive effect in that the response of sub-lethally hit tumor cells to damage might be required for therapy to be successful because the survival of cells communicating with irradiated cells is reduced.
authors.affiliation: Hospital Universitario Virgen de la Victoria, Unidad de Gestión Clínica de Oncología, Málaga, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Gómez-Millán
authors.forename: Iana Suly Santos
authors.initials: IS
authors.lastname: Katz
authors.forename: Virgínea de Araujo
authors.initials: Vde A
authors.lastname: Farias
authors.forename: Jose-Luis
authors.initials: JL
authors.lastname: Linares-Fernández
authors.forename: Jesús
authors.initials: J
authors.lastname: López-Peñalver
authors.forename: Gustavo
authors.initials: G
authors.lastname: Ortiz-Ferrón
authors.forename: Carmen
authors.initials: C
authors.lastname: Ruiz-Ruiz
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Oliver
authors.forename: José Mariano
authors.initials: JM
authors.lastname: Ruiz de Almodóvar
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D024201:Bystander Effect; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D053960:DNA Breaks; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008545:Melanoma / Q000473:pathology / Q000532:radiotherapy*; D059630:Mesenchymal Stem Cells / Q000528:radiation effects*; D011836:Radiation Tolerance; D012878:Skin Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D014470:Umbilical Cord / Q000166:cytology*