title: Different effects of carbon ion beams and X-rays on clonogenic survival and DNA repair in human pancreatic cancer stem-like cells.
abstract: OBJECTIVE
  The effects of a carbon ion beam and X-rays on human pancreatic cancer stem-like cells were examined from the point of view of clonogenic survival and DNA repair.
  
  
  METHODS
  Human pancreatic cancer stem-like cells were treated with and without carbon ion and X-ray irradiation, and then colony, spheroid and tumor formation assays as well as γH2AX foci formation assay were performed.
  
  
  RESULTS
  The relative biological effectiveness (RBE) values of a carbon ion beam relative to X-ray for the MIA PaCa-2 and BxPc-3 cells at the D10 values were 1.85-2.10. The ability for colony, spheroid formation, and tumorigenicity from cancer stem-like CD44(+)/CD24(+) cells is significantly higher than that from non-cancer stem-like CD44(-)/CD24(-)cells. FACS data showed that CD44(+)/CD24(+) cells were more highly enriched after X-rays compared to carbon ion irradiation at isoeffective doses. The RBE values for the carbon ion beam relative to X-ray at the D10 levels for CD44(+)/CD24(+) cells were 2.0-2.19. The number of γH2AX foci in CD44(-)/CD24(-) cells was higher than that of CD44(+)/CD24(+) cells after irradiation with either X-ray or carbon ion beam. The number of γH2AX foci in CD44(+)/CD24(+) cells was almost the same in the early time, but it persists significantly longer in carbon ion beam irradiated cells compared to X-rays.
  
  
  CONCLUSIONS
  Carbon ion beam has superior potential to kill pancreatic cancer stem cell-like cells, and prolonged induction of DNA damage might be one of the pivotal mechanisms of its high radiobiological effects compared to X-rays.
authors.affiliation: Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Oonishi
authors.forename: Xing
authors.initials: X
authors.lastname: Cui
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirakawa
authors.forename: Akira
authors.initials: A
authors.lastname: Fujimori
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kamijo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kamada
mesh_terms: D000818:Animals; D051927:CD24 Antigen / Q000032:analysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects*; D063193:Heavy Ion Radiotherapy; D006657:Histones / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D014411:Neoplastic Stem Cells / Q000528:radiation effects*; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D014964:X-Ray Therapy
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; C468783:H2AX protein, human; D006657:Histones; D018960:Hyaluronan Receptors