Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy

• Published in: Scientific reports Vol. 6; no. 1; p. 22275
• Main Authors: Oike, Takahiro, Niimi, Atsuko, Okonogi, Noriyuki, Murata, Kazutoshi, Matsumura, Akihiko, Noda, Shin-Ei, Kobayashi, Daijiro, Iwanaga, Mototaro, Tsuchida, Keisuke, Kanai, Tatsuaki, Ohno, Tatsuya, Shibata, Atsushi, Nakano, Takashi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2016; Nature Publishing Group
• Subjects: 14/34; 14/63; 631/337/1427/2122; 631/67/1059/485; Adult; Aged; Biopsy; Carbon; Cell Death - radiation effects; Chromosomes; Deoxyribonucleic acid; DNA; DNA - ultrastructure; DNA Breaks, Double-Stranded - radiation effects; DNA damage; Energy transfer; Female; Heavy Ion Radiotherapy; Humanities and Social Sciences; Humans; Linear Energy Transfer; Microscopy; multidisciplinary; Radiation therapy; Science; Tumor Burden - radiation effects; Tumor Suppressor p53-Binding Protein 1 - immunology; Tumors; Uterine Cervical Neoplasms - radiotherapy; Uterine Cervical Neoplasms - ultrastructure; X-Ray Therapy; X-rays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep22275

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.