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

被引：55

作者：

Oike, Takahiro ^{[1
,2
]}

Niimi, Atsuko ^{[3
]}

Okonogi, Noriyuki ^{[1
]}

Murata, Kazutoshi ^{[1
,2
]}

Matsumura, Akihiko ^{[2
]}

Noda, Shin-Ei ^{[1
,2
]}

Kobayashi, Daijiro ^{[1
]}

Iwanaga, Mototaro ^{[1
]}

Tsuchida, Keisuke ^{[1
]}

Kanai, Tatsuaki ^{[2
]}

Ohno, Tatsuya ^{[2
]}

Shibata, Atsushi ^{[4
]}

Nakano, Takashi ^{[1
,2
]}

机构：

[1] Gunma Univ, Grad Sch Med, Dept Radiat Oncol, 3-39-22 Showa Machi, Maebashi, Gunma 3718511, Japan

[2] Gunma Univ, Heavy Ion Med Ctr, 3-39-22 Showa Machi, Maebashi, Gunma 3718511, Japan

[3] Gunma Univ, Initiat Adv Res, Div Integrated Oncol Res, Res Program Heavy Ion Therapy, 3-39-22 Showa Machi, Maebashi, Gunma 3718511, Japan

[4] Gunma Univ, Adv Sci Res Leaders Dev Unit, 3-39-22 Showa Machi, Maebashi, Gunma 3718511, Japan

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

日本学术振兴会;

关键词：

HOMOLOGOUS RECOMBINATION REPAIR; GAMMA-H2AX; SIMULATION; RADIOSENSITIVITY; EXPOSURE;

D O I：

10.1038/srep22275

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：7

共 28 条

[1] GEANT4-a simulation toolkit [J].

Agostinelli, S ;

Allison, J ;

Amako, K ;

Apostolakis, J ;

Araujo, H ;

Arce, P ;

Asai, M ;

Axen, D ;

Banerjee, S ;

Barrand, G ;

Behner, F ;

Bellagamba, L ;

Boudreau, J ;

Broglia, L ;

Brunengo, A ;

Burkhardt, H ;

Chauvie, S ;

Chuma, J ;

Chytracek, R ;

Cooperman, G ;

Cosmo, G ;

Degtyarenko, P ;

Dell'Acqua, A ;

Depaola, G ;

Dietrich, D ;

Enami, R ;

Feliciello, A ;

Ferguson, C ;

Fesefeldt, H ;

Folger, G ;

Foppiano, F ;

Forti, A ;

Garelli, S ;

Giani, S ;

Giannitrapani, R ;

Gibin, D ;

Cadenas, JJG ;

González, I ;

Abril, GG ;

Greeniaus, G ;

Greiner, W ;

Grichine, V ;

Grossheim, A ;

Guatelli, S ;

Gumplinger, P ;

Hamatsu, R ;

Hashimoto, K ;

Hasui, H ;

Heikkinen, A ;

Howard, A .

NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT, 2003, 506 (03) :250-303

[2] Geant4 developments and applications [J].

Allison, J ;

Amako, K ;

Apostolakis, J ;

Araujo, H ;

Dubois, PA ;

Asai, M ;

Barrand, G ;

Capra, R ;

Chauvie, S ;

Chytracek, R ;

Cirrone, GAP ;

Cooperman, G ;

Cosmo, G ;

Cuttone, G ;

Daquino, GG ;

Donszelmann, M ;

Dressel, M ;

Folger, G ;

Foppiano, F ;

Generowicz, J ;

Grichine, V ;

Guatelli, S ;

Gumplinger, P ;

Heikkinen, A ;

Hrivnacova, I ;

Howard, A ;

Incerti, S ;

Ivanchenko, V ;

Johnson, T ;

Jones, F ;

Koi, T ;

Kokoulin, R ;

Kossov, M ;

Kurashige, H ;

Lara, V ;

Larsson, S ;

Lei, F ;

Link, O ;

Longo, F ;

Maire, M ;

Mantero, A ;

Mascialino, B ;

McLaren, I ;

Lorenzo, PM ;

Minamimoto, K ;

Murakami, K ;

Nieminen, P ;

Pandola, L ;

Parlati, S ;

Peralta, L .

IEEE TRANSACTIONS ON NUCLEAR SCIENCE, 2006, 53 (01) :270-278

[3] The EGFR mutation status affects the relative biological effectiveness of carbon-ion beams in non-small cell lung carcinoma cells [J].

Amornwichet, Napapat ;

Oike, Takahiro ;

Shibata, Atsushi ;

Nirodi, Chaitanya S. ;

Ogiwara, Hideaki ;

Makino, Haruhiko ;

Kimura, Yuka ;

Hirota, Yuka ;

Isono, Mayu ;

Yoshida, Yukari ;

Ohno, Tatsuya ;

Kohno, Takashi ;

Nakano, Takashi .

SCIENTIFIC REPORTS, 2015, 5

[4] Carbon-Ion Beam Irradiation Kills X-Ray-Resistant p53-Null Cancer Cells by Inducing Mitotic Catastrophe [J].

Amornwichet, Napapat ;

Oike, Takahiro ;

Shibata, Atsushi ;

Ogiwara, Hideaki ;

Tsuchiya, Naoto ;

Yamauchi, Motohiro ;

Saitoh, Yuka ;

Sekine, Ryota ;

Isono, Mayu ;

Yoshida, Yukari ;

Ohno, Tatsuya ;

Kohno, Takashi ;

Nakano, Takashi .

PLOS ONE, 2014, 9 (12)

[5] Biological characteristics of carbon-ion therapy [J].

Ando, Koichi ;

Kase, Yuki .

INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2009, 85 (09) :715-728

[6] Unrepaired clustered DNA lesions induce chromosome breakage in human cells [J].

Asaithamby, Aroumougame ;

Hu, Burong ;

Chen, David J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (20) :8293-8298

[7]

Aso T, 2007, IEEE NUCL SCI CONF R, P2564

[8] Radiosensitivity in breast cancer assessed by the histone γ-H2AX and 53BP1 foci [J].

Djuzenova, Cholpon S. ;

Elsner, Ines ;

Katzer, Astrid ;

Worschech, Eike ;

Distel, Luitpold V. ;

Flentje, Michael ;

Polat, Buelent .

RADIATION ONCOLOGY, 2013, 8

[9]

DOE-NCI, 2013, WORKSH ION BEAM THER

[10] γH2AX foci analysis for monitoring DNA double-strand break repair Strengths, limitations and optimization [J].

Loebrich, Markus ;

Shibata, Atsushi ;

Beucher, Andrea ;

Fisher, Anna ;

Ensminger, Michael ;

Goodarzi, Aaron A. ;

Barton, Olivia ;

Jeggo, Penny A. .

CELL CYCLE, 2010, 9 (04) :662-669

← 1 2 3 →