Cellular and molecular effects of protons:: Apoptosis induction and potential implications for cancer therapy
Cellular and molecular effects of protons:: Apoptosis induction and potential implications for cancer therapy
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DOI：
10.1007/s10495-005-3346-1
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发表时间：
2006-01-01
期刊：
影响因子：
7.2
通讯作者：
Purrello, M
中科院分区：
文献类型：
--
作者：
Di Pietro, C;Piro, S;Purrello, M
由于质子的弹道精确性，质子诱导细胞凋亡可能是特异性消除肿瘤细胞的一种策略。为了表征这些强子的细胞和分子效应，我们通过将不同的细胞系（PC3、Ca301D、MCF7）暴露于增加剂量的质子中并使用 FACS、RT-PCR 和电子自旋共振 (ESR) 检查它们来进行剂量反应和时程实验。使用 10 Gy 剂量的 26,7 Mev 质子束进行照射会改变细胞膜等结构，引起 DNA 双链断裂，并显着增加细胞内羟基离子（活性氧 (ROS)）的水平。这改变了受辐射细胞的转录组，激活了细胞凋亡的线粒体（内在）途径，并导致细胞周期停滞在 G2/M 边界。与对照组相比，受辐射细胞群内坏死细胞的数量没有显着增加。 20 Gy 照射的效果在定性和定量上相似，但暴露于 40 Gy 会导致大量坏死。类似的光子实验表明，它们能以显着较低的数量且以时间延迟的方式诱导细胞凋亡。这些数据增进了我们对质子照射的细胞和分子效应的了解，并可用于改进当前的强子治疗方案。
Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols.