Keta Otilija D, Todorović Danijela V, Bulat Tanja M, Cirrone Pablo Ga, Romano Francesco, Cuttone Giacomo, Petrović Ivan M, Ristić Fira Aleksandra M
1 Vinča Institute of Nuclear Sciences, University of Belgrade, Belgrade 11001, Serbia.
2 Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia.
Exp Biol Med (Maywood). 2017 May;242(10):1015-1024. doi: 10.1177/1535370216669611. Epub 2016 Sep 15.
The aim of this study was to investigate effects of irradiations with the therapeutic proton and carbon ion beams in two non-small cell lung cancers, CRL5876 adenocarcinoma and HTB177 large cell lung carcinoma. The DNA damage response dynamics, cell cycle regulation, and cell death pathway activation were followed. Viability of both cell lines was lower after carbon ions compared to the therapeutic proton irradiations. HTB177 cells showed higher recovery than CRL5876 cells seven days following the treatments, but the survival rates of both cell lines were lower after exposure to carbon ions with respect to therapeutic protons. When analyzing cell cycle distribution of both CRL5876 and HTB177 cells, it was noticed that therapeutic protons predominantly induced G1 arrest, while the cells after carbon ions were arrested in G2/M phase. The results illustrated that differences in the levels of phosphorylated H2AX, a double-strand break marker, exist after therapeutic proton and carbon ion irradiations. We also observed dose- and time-dependent increase in the p53 and p21 levels after applied irradiations. Carbon ions caused larger increase in the quantity of p53 and p21 compared to therapeutic protons. These results suggested that various repair mechanisms were induced in the treated cells. Considering the fact that we have not observed any distinct change in the Bax/Bcl-2 ratio following irradiations, it seemed that different types of cell death were involved in the response to the two types of irradiations that were applied.
本研究的目的是调查治疗性质子束和碳离子束照射对两种非小细胞肺癌(CRL5876腺癌和HTB177大细胞肺癌)的影响。跟踪DNA损伤反应动力学、细胞周期调控和细胞死亡途径激活情况。与治疗性质子照射相比,碳离子照射后两种细胞系的活力均较低。治疗后7天,HTB177细胞的恢复情况比CRL5876细胞更好,但与治疗性质子照射相比,两种细胞系在接受碳离子照射后的存活率均较低。在分析CRL5876和HTB177细胞的细胞周期分布时,发现治疗性质子主要诱导G1期阻滞,而碳离子照射后的细胞则阻滞在G2/M期。结果表明,治疗性质子和碳离子照射后,双链断裂标志物磷酸化H2AX的水平存在差异。我们还观察到照射后p53和p21水平呈剂量和时间依赖性增加。与治疗性质子相比,碳离子导致p53和p21的量增加更大。这些结果表明,处理后的细胞诱导了各种修复机制。鉴于我们在照射后未观察到Bax/Bcl-2比值有任何明显变化,似乎两种照射方式所引发的细胞死亡反应涉及不同类型的细胞死亡。