Department of Radiology, University of Erlangen-Nürnberg, Maximiliansplatz 1, D-91054 Erlangen, Germany.
Radiology. 2012 Jul;264(1):59-67. doi: 10.1148/radiol.12111730. Epub 2012 Apr 16.
To investigate the effect of a radioprotective oral agent containing a formulation of antioxidants and glutathione-elevating compounds on the extent of x-ray-induced γ-H2AX foci formation.
The study was approved by local ethics committee and informed consent was obtained from each subject. In vitro experiments with blood lymphocytes of 25 healthy volunteers were performed without antioxidants and with antioxidants added either before or immediately after irradiation (10 mGy). For in vivo/in vitro tests, blood samples were obtained before, 15, 30, and 60 minutes (n=17) after, and 2, 3, and 5 hours (n=11) after oral ingestion of antioxidant pills and were irradiated (10 mGy). DNA double-strand breaks (DSBs) were quantified in isolated lymphocytes 5 minutes (in vitro and in vivo/in vitro) and 15 minutes (in vitro) after irradiation by enumerating γ-H2AX foci. To validate the data, additional in vitro experiments with use of 53BP1 as another independent marker for DSBs were performed. Nonirradiated samples served as controls. Statistical analyses were performed by using Wilcoxon rank-sum tests (in vitro), repeated-measures test, and Dunnett test (in vivo/in vitro).
In the in vitro experiments, 15-minute preincubation with antioxidants significantly reduced mean γ-H2AX foci levels by 23% (P<.0001), whereas addition of antioxidants immediately after irradiation did not lead to a reduction of x-ray-induced foci (P=.6905). Mean 53BP1 foci were also reduced by preincubation with the radioprotectant. In the in vivo/in vitro tests, oral pretreatment with antioxidants also led to a significant reduction of γ-H2AX foci formation; administration 60 minutes before irradiation resulted in a mean foci reduction of 58% (P<.0001).
The tested formulation of antioxidants significantly reduced formation of γ-H2AX and 53BP1 foci after irradiation at a radiologic radiation dose typical for computed tomographic imaging; administration 60 minutes prior to irradiation seems to be appropriate and leads to a significant reduction in foci.
研究一种含有抗氧化剂和谷胱甘肽提升化合物配方的放射防护口服剂对 X 射线诱导 γ-H2AX 焦点形成程度的影响。
本研究获得了当地伦理委员会的批准，并获得了每位受试者的知情同意。在没有抗氧化剂的情况下，对 25 名健康志愿者的血液淋巴细胞进行了体外实验，并在辐照前（10mGy）或辐照后立即添加抗氧化剂进行了实验。对于体内/体外试验，在口服抗氧化丸后 15、30 和 60 分钟（n=17）以及 2、3 和 5 小时（n=11）时采集血样，并进行辐照（10mGy）。通过计数 γ-H2AX 焦点，在辐照后 5 分钟（体外和体内/体外）和 15 分钟（体外）时，从分离的淋巴细胞中定量评估 DNA 双链断裂（DSBs）。为了验证数据，还进行了使用 53BP1 作为 DSBs 的另一个独立标志物的额外体外实验。未辐照的样本作为对照。通过使用 Wilcoxon 秩和检验（体外）、重复测量检验和 Dunnett 检验（体内/体外）进行统计分析。
在体外实验中，15 分钟的预孵育与抗氧化剂显著降低了平均 γ-H2AX 焦点水平 23%（P<.0001），而辐照后立即添加抗氧化剂不会导致 X 射线诱导焦点减少（P=.6905）。预孵育与放射防护剂也降低了平均 53BP1 焦点。在体内/体外试验中，抗氧化剂的口服预处理也导致 γ-H2AX 焦点形成的显著减少；在辐照前 60 分钟给药导致平均焦点减少 58%（P<.0001）。
在典型的计算机断层扫描成像放射剂量下，经测试的抗氧化剂配方显著减少了 γ-H2AX 和 53BP1 焦点的形成；在辐照前 60 分钟给药似乎是合适的，并导致焦点显著减少。
