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γ射线和碳离子束辐照后肺腺癌 A549 细胞中的 DNA 损伤反应信号转导

DNA damage response signaling in lung adenocarcinoma A549 cells following gamma and carbon beam irradiation.

机构信息

Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai, India.

出版信息

Mutat Res. 2011 Nov 1;716(1-2):10-9. doi: 10.1016/j.mrfmmm.2011.07.015. Epub 2011 Aug 3.

DOI:10.1016/j.mrfmmm.2011.07.015
PMID:21839752
Abstract

Carbon beams (5.16MeV/u, LET=290keV/μm) are high linear energy transfer (LET) radiation characterized by higher relative biological effectiveness than low LET radiation. The aim of the current study was to determine the signaling differences between γ-rays and carbon ion-irradiation. A549 cells were irradiated with 1Gy carbon or γ-rays. Carbon beam was found to be three times more cytotoxic than γ-rays despite the fact that the numbers of γ-H2AX foci were same. Percentage of cells showing ATM/ATR foci were more with γ-rays however number of foci per cell were more in case of carbon irradiation. Large BRCA1 foci were found in all carbon irradiated cells unlike γ-rays irradiated cells and prosurvival ERK pathway was activated after γ-rays irradiation but not carbon. The noteworthy finding of this study is the early phase apoptosis induction by carbon ions. In the present study in A549 lung adenocarcinoma, authors conclude that despite activation of same repair molecules such as ATM and BRCA1, differences in low and high LET damage responses might be due to their distinct macromolecular complexes rather than their individual activation and the activation of cytoplasmic pathways such as ERK, whether it applies to all the cell lines need to be further explored.

摘要

碳离子束(5.16MeV/u,LET=290keV/μm)具有较高的线性能量转移(LET),其相对生物效应高于低 LET 辐射。本研究旨在确定γ射线与碳离子辐照之间的信号差异。用 1Gy 的碳离子或γ射线辐照 A549 细胞。尽管γ-H2AX 焦点的数量相同,但碳离子束的细胞毒性是γ射线的三倍。表现出 ATM/ATR 焦点的细胞百分比γ射线更多,但每个细胞的焦点数量在碳辐照的情况下更多。与γ射线辐照的细胞不同,所有碳离子辐照的细胞中都发现了大的 BRCA1 焦点,并且 γ射线辐照后激活了促生存的 ERK 途径,但碳离子辐照后没有。本研究的一个显著发现是碳离子诱导的早期凋亡。在本研究中,作者在肺腺癌 A549 细胞中得出结论,尽管相同的修复分子(如 ATM 和 BRCA1)被激活,但低 LET 和高 LET 损伤反应的差异可能是由于它们独特的大分子复合物,而不是它们的单独激活和细胞质途径(如 ERK)的激活,这是否适用于所有细胞系需要进一步探索。

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