title: Carbon-ion beam irradiation kills X-ray-resistant p53-null cancer cells by inducing mitotic catastrophe.
abstract: OBJECTIVE
  To understand the mechanisms involved in the strong killing effect of carbon-ion beam irradiation on cancer cells with TP53 tumor suppressor gene deficiencies.
  
  
  METHODS
  DNA damage responses after carbon-ion beam or X-ray irradiation in isogenic HCT116 colorectal cancer cell lines with and without TP53 (p53+/+ and p53-/-, respectively) were analyzed as follows: cell survival by clonogenic assay, cell death modes by morphologic observation of DAPI-stained nuclei, DNA double-strand breaks (DSBs) by immunostaining of phosphorylated H2AX (γH2AX), and cell cycle by flow cytometry and immunostaining of Ser10-phosphorylated histone H3.
  
  
  RESULTS
  The p53-/- cells were more resistant than the p53+/+ cells to X-ray irradiation, while the sensitivities of the p53+/+ and p53-/- cells to carbon-ion beam irradiation were comparable. X-ray and carbon-ion beam irradiations predominantly induced apoptosis of the p53+/+ cells but not the p53-/- cells. In the p53-/- cells, carbon-ion beam irradiation, but not X-ray irradiation, markedly induced mitotic catastrophe that was associated with premature mitotic entry with harboring long-retained DSBs at 24 h post-irradiation.
  
  
  CONCLUSIONS
  Efficient induction of mitotic catastrophe in apoptosis-resistant p53-deficient cells implies a strong cancer cell-killing effect of carbon-ion beam irradiation that is independent of the p53 status, suggesting its biological advantage over X-ray treatment.
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan; Department of Radiology, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
authors.forename: Napapat
authors.initials: N
authors.lastname: Amornwichet
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan; Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oike
authors.affiliation: Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ogiwara
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Division of Radiation Biology and Protection, Atomic Bomb Disease Institute, Nagasaki University, Sakamoto, Nagasaki, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamauchi
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Saitoh
authors.affiliation: Advanced Scientific Research Leaders Development Unit, Gunma University, Maebashi, Gunma, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Sekine
authors.affiliation: Gunma University Heavy Ion Medical Center, Maebashi, Gunma, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Isono
authors.affiliation: Gunma University Heavy Ion Medical Center, Maebashi, Gunma, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Gunma University Heavy Ion Medical Center, Maebashi, Gunma, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D045325:HCT116 Cells; D063193:Heavy Ion Radiotherapy; D006657:Histones / Q000378:metabolism; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000528:radiation effects; D010766:Phosphorylation; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D006657:Histones; D016159:Tumor Suppressor Protein p53