Induction of in situ DNA double-strand breaks and apoptosis by 200 MeV protons and 10 MV X-rays in human tumour cell lines

Induction of in situ DNA double-strand breaks and apoptosis by 200 MeV protons and 10 MV X-rays in human tumour cell lines
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DOI:
10.3109/09553002.2010.518201
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发表时间:
2011-01-01
影响因子:
2.6
通讯作者:
Tsuboi, Koji
Tsuboi, Koji
中科院分区:
医学3区
文献类型:
--
作者:
Gerelchuluun, Ariungerel;Hong, Zhengshan;Tsuboi, Koji

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目的:通过与临床高能X射线的比较,阐明临床高能质子的性质。材料和方法:用200 MeV质子或10 mV X射线照射人肿瘤细胞株ONS76和MOLT4。用磷酸化组蛋白H_2AX(γ-H_2AX)免疫细胞化学染色评价原位DNA双链断裂(DDSB)诱导作用。结果:照射后30min质子诱导率明显高于X射线,平均比值分别为1.28(ONS76)和1.59(MOLT4)。质子对MOLT4细胞的凋亡诱导作用在12h时显著高于X射线,12h时平均为2.13,20h时差异不显著,10%存活率时质子对X射线的RBE值分别为1.06+/-0.04和1.02+/-0.15。在早期阶段,质子束显示出比X射线更高的细胞失活。这些数据可能有助于理解临床质子束的生物学特性。
Purpose: To clarify the properties of clinical high-energy protons by comparing with clinical high-energy X-rays.Materials and methods: Human tumor cell lines, ONS76 and MOLT4, were irradiated with 200 MeV protons or 10 MV X-rays. In situ DNA double-strand breaks (DDSB) induction was evaluated by immunocytochemical staining of phosphorylated histone H2AX (gamma-H2AX). Apoptosis was measured by flow-cytometry after staining with Annexin V. The relative biological effectiveness (RBE) was obtained by clonogenic survival assay.Results: DDSB induction was significantly higher for protons than X-rays with average ratios of 1.28 (ONS76) and 1.59 (MOLT4) at 30 min after irradiation. However the differences became insignificant at 6 h. Also, apoptosis induction in MOLT4 cells was significantly higher for protons than X-rays with an average ratio of 2.13 at 12 h. However, the difference became insignificant at 20 h. RBE values of protons to X-rays at 10% survival were 1.06 +/- 0.04 and 1.02 +/- 0.15 for ONS76 and MOLT4, respectively.Conclusions: Cell inactivation may differ according to different timings and/or endpoints. Proton beams demonstrated higher cell inactivation than X-rays in the early phases. These data may facilitate the understanding of the biological properties of clinical proton beams.