title: Gemcitabine Induces Radiosensitization Through Inhibition of RAD51-dependent Repair for DNA Double-strand Breaks.
abstract: OBJECTIVE
  Gemcitabine (GEM) is used in clinical chemo-radiotherapy; however, the mechanism that contributes to enhanced radiosensitivity by GEM is not fully-understood. We evaluated the effect of GEM on radiosensitization in pancreatic cancer cell lines.
  
  
  METHODS
  Pancreatic cell lines PK-59 and PK-45p were used. A total of 5 μM GEM for 4 h were administered pre- or post-gamma irradiation.
  
  
  RESULTS
  Enhanced cell killing effects by GEM in radiotherapy were observed for pre-treatment but not post-treatment GEM. We focused on the dynamics of RAD51 and phospho-H2AX foci after irradiation. Significantly higher numbers of phospho-H2AX foci were observed in GEM pre-treated cells than in untreated cells after irradiation. We also found inhibition of the formation and degradation of RAD51 foci by GEM pre-treatment. The radiosensitizing effect of GEM was suppressed by knockdown of RAD51.
  
  
  CONCLUSIONS
  RAD51-dependent homologous recombination is one of the key targets in the GEM-induced radiosensitizing effect.
authors.affiliation: Department of Radiology, School of Medicine, Oita University, Oita, Japan.
authors.forename: Shinko
authors.initials: S
authors.lastname: Kobashigawa
authors.affiliation: Department of Radiological Science, Faculty of Health Science, Junshin Gakuen University, Fukuoka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Morikawa
authors.affiliation: Department of Radiology, School of Medicine, Oita University, Oita, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Mori
authors.affiliation: Advanced Molecular Imaging Center, School of Medicine, Oita University, Oita, Japan kashino@oita-u.ac.jp.
authors.forename: Genro
authors.initials: G
authors.lastname: Kashino
mesh_terms: D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005720:Gamma Rays; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents; D000093542:Gemcitabine
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: RAD51; Radiosensitization; gemcitabine; homologous recombination