High LET Radiation Enhances Nocodazole Induced Cell Death in HeLa Cells through Mitotic Catastrophe and Apoptosis
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概要
- 論文の詳細を見る
To understand how human tumor cells respond to the combined treatment with nocodazole and high LET radiation, alterations in cell cycle, mitotic disturbances and cell death were investigated in the present study. Human cervix carcinoma HeLa cells were exposed to nocodazole for 18 h immediately followed by high LET iron ion irradiation and displayed a sequence of events leading to DNA damages, mitotic aberrations, interphase restitution and endocycle as well as cell death. A prolonged mitotic arrest more than 10 h was observed following nocodazole exposure, no matter the irradiation was present or not. The occurrence of mitotic slippage following the mitotic arrest was only drug-dependent and the irradiation did not accelerate it. The amount of polyploidy cells was increased following mitotic slippage. No detectable G2 or G1 arrest was observed in cells upon the combined treatment and the cells reentered the cell cycle still harboring unrepaired cellular damages. This premature entry caused an increase of multipolar mitotic spindles and amplification of centrosomes, which gave rise to lagging chromosomal material, failure of cytokinesis and polyploidization. These mitotic disturbances and their outcomes confirmed the incidence of mitotic catastrophe and delayed apoptotic features displayed by TUNEL method after the combined treatment. These results suggest that the addition of high-LET iron ion irradiation to nocodazole enhanced mitotic catastrophe and delayed apoptosis in HeLa cells. These might be important cell death mechanisms involved in tumor cells in response to the treatment of antimitotic drug combined with high LET radiation.
- Journal of Radiation Research 編集委員会の論文
著者
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FURUSAWA Yoshiya
Heavy-ion Radiobiology Research Group, Research Center for Charged Particle Therapy, National Instit
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MATSUMOTO Yoshitaka
Heavy-ion Radiobiology Research Group, National Institute of Radiological Sciences
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Furusawa Yoshiya
Heavy-ion Radiobiology Res. Group National Inst. Of Radiological Sciences
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Li Ping
Key Lab. Of Heavy Ion Radiation Biology And Medicine Of Chinese Acad. Of Sciences
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LI Ping
Institute of Modern Physics, Chinese Academy of Sciences
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ZHOU Libin
Institute of Modern Physics, Chinese Academy of Sciences
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DAI Zhongying
Institute of Modern Physics, Chinese Academy of Sciences
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JIN Xiaodong
Institute of Modern Physics, Chinese Academy of Sciences
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LIU Xinguo
Institute of Modern Physics, Chinese Academy of Sciences
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LI Qiang
Institute of Modern Physics, Chinese Academy of Sciences
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Li Ping
Institute Of Modern Physics Chinese Academy Of Sciences
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Li Qiang
Institute Of Modern Physics Chinese Academy Of Sciences
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Matsumoto Yoshitaka
Heavy-ion Radiobiology Res. Group National Inst. Of Radiological Sciences
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Jin Xiaodong
Institute Of Modern Physics Chinese Academy Of Sciences
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Dai Zhongying
Institute Of Modern Physics Chinese Academy Of Sciences
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