pATM and γH2AX are effective radiation biomarkers in assessing the radiosensitivity of (12)C(6+) in human tumor cells.
pATM and γH2AX are effective radiation biomarkers in assessing the radiosensitivity of (12)C(6+) in human tumor cells.
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DOI：
10.1186/s12935-017-0419-5
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发表时间：
2017
影响因子：
5.8
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Zhao J;Guo Z;Pei S;Song L;Wang C;Ma J;Jin L;Ma Y;He R;Zhong J;Ma Y;Zhang H
肿瘤放射敏感性在优化放射治疗期间的辐射剂量方面特别有用。本研究旨在评价磷酸化H2 AX（γ H2 AX）和ATM（pATM）在评价肿瘤细胞12 C6+放射敏感性中的潜在价值。用不同剂量的12 C6+照射人宫颈癌HeLa细胞、肝癌HepG 2细胞和粘液表皮样癌MEC-1细胞。用克隆形成存活法测定细胞存活分数，用免疫细胞化学方法观察γ H2 AX和pATM灶。流式细胞仪检测γ H2 AX、pATM和细胞周期。12 C6+照射后24 h内，细胞存活分数呈剂量依赖性下降，而24 h内细胞存活分数又显著上升。γ H2 AX和pATM的聚集点均随剂量的增加而线性增加，γ H2 AX和pATM分别在0.5 h和0.5 h或4 h达到最大诱导量，部分聚集点可持续24 h。γ H2 AX和pATM的表达与细胞周期有关。γ H2 AX在G 0/G1期细胞中的表达在照射后0.5h最高，24 h后下降至较低水平。2、4戈伊照射24 h后，G2/M期pATM明显增加。G2/M期阻滞明显。γ H2 AX和pATM的表达与12 C6+诱导的克隆形成的存活率在时间和剂量上都有密切关系。γ H2 AX和pATM的形成和丢失速率可能是细胞对12 C6+反应的重要因素。pATM和γ H2 AX是评价肿瘤细胞12 C6+放射敏感性的有效放射生物标志物。
Tumour radiosensitivity would be particularly useful in optimizing the radiation dose during radiotherapy. The aim of the current study was to evaluate the potential value of phosphorylated H2AX (γH2AX) and ATM (pATM) in assessing 12C6+ radiosensitivity of tumour cells. Human cervical carcinoma HeLa cells, hepatoma HepG2 cells, and mucoepidermoid carcinoma MEC-1 cells were irradiated with different doses of 12C6+. The survival fraction was assayed with clonogenic survival method and the foci of γH2AX and pATM was visualized using immunocytochemical methods. Flow cytometry was used to assay γH2AX, pATM and the cell cycle. The survival fraction decreased immediately in dose-dependent manner, but in turn, significantly increased during 24 h after 12C6+ irradiation. Both γH2AX and pATM foci accumulated linearly with doses and with a maximum induction at 0.5 h for γH2AX and 0.5 or 4 h for pATM, respectively, and a fraction foci kept for 24 h. The expression of γH2AX and pATM was in relation to cell cycle. The G0/G1 phase cells had the highest expression of γH2AX after 0.5 h irradiation and then decreased to a lower level at 24 h after irradiation. An obvious increase of pATM in G2/M phase was shown after 24 h of 2 and 4 Gy irradiation. The significant G2/M phase arrest was shown. There was a close relationship between the clonogenic survival and γH2AX and pATM expression both in timing and dose in response to 12C6+. The rate of γH2AX and pATM formation and loss may be an important factor in the response of cells to 12C6+. pATM and γH2AX are effective radiation biomarkers in assessing the radiosensitivity of 12C6+ in human tumor cells.