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二维单层和三维人体血管模型中 DNA 损伤焦点的形成和减少:根据辐射质量的不同影响。

DNA damage foci formation and decline in two-dimensional monolayers and in three-dimensional human vessel models: differential effects according to radiation quality.

机构信息

Center for Radiological Research, College of Physicians and Surgeons, Columbia University, NY 10032, USA.

出版信息

Int J Radiat Biol. 2012 Jun;88(6):493-500. doi: 10.3109/09553002.2012.679382. Epub 2012 Apr 30.

DOI:10.3109/09553002.2012.679382
PMID:22449005
Abstract

PURPOSE

To analyze the effect of different radiation qualities on the kinetics of p53 Binding Protein 1 (53BP1) formation and decline in human three-dimensional (3-D) vessel models.

MATERIAL AND METHODS

Two-dimensional (2-D) and 3-D cultures of human umbilical vein cells were exposed to 80 cGy of Gamma radiation and high-energy protons and Fe ions. 53BP1 antibodies were used for foci visualization via immunocytochemistry. Computer analysis was used to determine the number and the size of foci up to 48 hours after irradiation.

RESULTS

DNA foci kinetics in 2-D and 3-D human vessel cultures show that foci formation and removal were the same in each type of culture. After 48 h, the number of foci induced by high-energy protons and gamma rays reduced to almost control levels while high linear energy transfer (LET) Fe particles produced more persistent damage.

CONCLUSION

The kinetics of radiation-induced 53BP1 foci in 3-D vessel models is essentially the same as in 2-D monolayers. Since the basal level of spontaneous foci is low in these differentiated non-proliferating cultures, the persistence of radiation-induced 53BP1 foci is detected longer than previously noted. Furthermore, analysis of foci sizes revealed that abnormal radiation-induced foci can persist even when foci frequencies are close to basal levels. The detection of these latent abnormalities could be useful for a more sensitive dosimetry.

摘要

目的

分析不同辐射质量对人三维(3-D)血管模型中 p53 结合蛋白 1(53BP1)形成和减少的动力学的影响。

材料和方法

用 80cGyγ射线和高能质子及 Fe 离子照射人脐静脉细胞的二维(2-D)和三维(3-D)培养物。用 53BP1 抗体通过免疫细胞化学法进行焦点可视化。用计算机分析在照射后 48 小时内确定焦点的数量和大小。

结果

2-D 和 3-D 人血管培养物中的 DNA 焦点动力学表明,每种培养物中的焦点形成和去除相同。48 小时后,高能质子和γ射线诱导的焦点数量减少到接近对照水平,而高线性转移(LET)Fe 粒子产生更持久的损伤。

结论

3-D 血管模型中辐射诱导的 53BP1 焦点的动力学与 2-D 单层基本相同。由于这些分化的非增殖培养物中自发焦点的基础水平较低,因此检测到的辐射诱导的 53BP1 焦点的持久性比以前注意到的更长。此外,焦点大小的分析表明,即使焦点频率接近基础水平,异常辐射诱导的焦点也可以持续存在。这些潜在异常的检测对于更敏感的剂量测定可能是有用的。

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