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200 MeV 质子和 10 MV X 射线诱导人肿瘤细胞系中 DNA 双链断裂和凋亡。

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

机构信息

Proton Medical Research Center, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.

出版信息

Int J Radiat Biol. 2011 Jan;87(1):57-70. doi: 10.3109/09553002.2010.518201. Epub 2010 Oct 18.

DOI:10.3109/09553002.2010.518201
PMID:20954835
Abstract

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 (γ-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.

摘要

目的

通过与临床高能 X 射线比较,阐明临床高能质子的特性。

材料与方法

采用 200MeV 质子和 10MVX 射线照射人肿瘤细胞系 ONS76 和 MOLT4。用磷酸化组蛋白 H2AX(γ-H2AX)免疫细胞化学染色评估原位 DNA 双链断裂(DDSB)的诱导。用 Annexin V 染色后通过流式细胞术测量细胞凋亡。通过集落形成存活实验获得相对生物效应(RBE)。

结果

照射后 30min,DDSB 的诱导质子明显高于 X 射线,平均比值分别为 1.28(ONS76)和 1.59(MOLT4)。然而,在 6h 后,差异变得不显著。同样,MOLT4 细胞中凋亡的诱导质子也明显高于 X 射线,平均比值为 2.13,在 12h。然而,在 20h 后,差异变得不显著。10%存活时质子相对于 X 射线的 RBE 值分别为 1.06±0.04 和 1.02±0.15。

结论

细胞失活可能因不同的时间和/或终点而异。在早期阶段,质子束比 X 射线具有更高的细胞失活能力。这些数据可能有助于理解临床质子束的生物学特性。

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