title: Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy.
abstract: Carbon ion radiotherapy shows great potential as a cure for X-ray-resistant tumors. Basic research suggests that the strong cell-killing effect induced by carbon ions is based on their ability to cause complex DNA double-strand breaks (DSBs). However, evidence supporting the formation of complex DSBs in actual patients is lacking. Here, we used advanced high-resolution microscopy with deconvolution to show that complex DSBs are formed in a human tumor clinically treated with carbon ion radiotherapy, but not in a tumor treated with X-ray radiotherapy. Furthermore, analysis using a physics model suggested that the complexity of radiotherapy-induced DSBs is related to linear energy transfer, which is much higher for carbon ion beams than for X-rays. Visualization of complex DSBs in clinical specimens will help us to understand the anti-tumor effects of carbon ion radiotherapy.
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oike
authors.affiliation: Research Program for Heavy Ion Therapy, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Niimi
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Okonogi
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Murata
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Matsumura
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Shin-Ei
authors.initials: SE
authors.lastname: Noda
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Daijiro
authors.initials: D
authors.lastname: Kobayashi
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Mototaro
authors.initials: M
authors.lastname: Iwanaga
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tsuchida
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Kanai
authors.affiliation: Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohno
authors.affiliation: Advanced Scientific Research Leaders Development Unit, Gunma University, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shibata
authors.affiliation: Department of Radiation Oncology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.|Gunma University Heavy Ion Medical Center, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D016923:Cell Death / Q000528:radiation effects; D004247:DNA / Q000648:ultrastructure*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D005260:Female; D063193:Heavy Ion Radiotherapy; D006801:Humans; D018499:Linear Energy Transfer; D008853:Microscopy; D047368:Tumor Burden / Q000528:radiation effects; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy* / Q000648:ultrastructure; D014964:X-Ray Therapy
chemical_list: C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D004247:DNA