抗氧化药物对CT辐射导致DNA双链断裂预防效果及机制的研究

With the clinical application of CT more widely, people are more and more concerned about radiation safety. X-rays from CT examination can induce many types of DNA damage and may even cause cancer. In recent years, it has been discovered that a γ-H2AX protein capable of labeling DNA double-strand breaks which provides a reliable means for the biological study of radiation damage. Our study found that CT radiation can cause elevated levels of γ-H2AX protein in the peripheral blood lymphocytes of the examiner, and the degree of increase is positively correlated with the radiation dose. We found that taking vitamin C before the examination can reduce the γ-H2AX protein production in nuclear and reduce the degree of DNA double-strand breaks. Based on this, we propose a hypothesis that antioxidants can neutralize the free radicals produced by cells during radiation and reduce the DNA double-strand breaks caused by oxidative stress, thereby preventing radiation damage. In this project, in both in vitro experiments and in vivo experiments, from the molecular level and cell level, through observe the changes of γ-H2AX protein, oxidative stress related substances and cell status of lymphocytes in peripheral blood after radiation， to explore the effect and mechanism of anti-oxidant drugs to prevent radiation injury. This study will demonstrate from all-round that whether antioxidation drugs can prevent CT radiation damage and provide new ideas for the prevention of CT radiation damage.

CT检查带来的X射线可诱发多种类型的DNA损伤，甚至可能引起癌症的发生。近年来，人们发现了一种能够标记DNA双链断裂的γ-H2AX蛋白，为辐射损伤的生物学研究提供了可靠的手段。研究表明，CT辐射可以引起检查者外周血淋巴细胞中γ-H2AX蛋白水平升高，且升高的程度与辐射剂量呈正相关。我们发现在检查前服用维生素C后可以减少细胞核内γ-H2AX焦点产生，减轻DNA双链断裂程度。据此我们提出假说：抗氧化剂可以中和细胞接受辐射后产生的自由基的，减轻氧化应激导致的DNA双链断裂，从而起到辐射损伤预防的作用。本项目拟通过体外实验及体内实验，从分子水平及细胞水平，观察辐射后外周血中淋巴细胞中γ-H2AX蛋白、氧化应激相关物质及细胞状态的变化，探讨抗氧化药物预防辐射损伤的效果及其作用机制。本研究将从全方位论证抗氧化药物能否预防CT辐射损伤，为CT辐射损伤的预防提供新思路。

CT检查带来的X射线可诱发多种类型的DNA损伤，甚至可能引起癌症的发生。近年来，人们发现了一种能够标记DNA双链断裂的γ-H2AX蛋白，为辐射损伤的生物学研究提供了新方法。同时，抗氧化药物被发现能够减少辐射损伤相关蛋白，为辐射损伤预防提供了新思路。在本项研究中，我们通过细胞实验、动物实验及临床研究，由粗到细，逐步筛选最有效、最合理的抗氧化药物预防方案。同时，使用尝试使用多维度的生物学方法解释辐射预防机制。口服或静脉使用N-乙酰半胱氨酸和维生素C有可以有效减轻CT辐射生物损伤。CT检查前3h，口服1g维生素C泡腾片可降低潜在生物损伤。在低剂量CT辐射下，在细胞实验中，N-乙酰半胱氨酸、维生素C及氨磷汀减轻DSBs效果较好。在动物实验中，N-乙酰半胱氨酸和维生素C均可以通过降低细胞内的氧化应激，减少外周血淋巴细胞中DSBs、24h后微核个数。在临床实验中，维生素C发现可以减少H2AX及53BP共定位焦点个数约36%，改变基因表达情况。提示预防性使用抗氧化药物，可以降低低剂量CT检查中、核辐射或其他低剂量辐射暴露过程中的生物损伤，有潜在应用价值。