Abstract—

The individual differences in the efficiency of the DNA DSB repair have been evaluated in lymphocytes of patients with amnestic mild cognitive impairment (AMCI) and Alzheimer’s disease (AD) and of healthy volunteers by the level of residual γH2AX foci after γ-irradiation at a dose of 2 Gy. Lymphocytes isolated from the peripheral blood of the examined patients were frozen in a cell freezing medium. Before the study, the frozen lymphocytes were thawed, suspended in the RPMI 1640 medium supplemented with 10% inactivated fetal bovine serum, and subdivided into two halves. One half was γ-irradiated using a ⁶⁰Co source on a GUT-200M facility at a dose of 2 Gy (a dose rate of 0.75 Gy/min) at 4°C. Control and irradiated lymphocytes were then cultured for 24 h, collected, fixed, and stored until the study of the number of spontaneous and residual foci of γH2AX performed using fluorescent microscopy after staining with fluorescent labeled antibodies. An increased number of residual γH2AX foci in lymphocytes as well as an increased number of lymphocytes containing such foci were found in AMCI and АD patients as compared with healthy volunteers. This suggests a decrease in the ability of the DNA DSB repair in these patients. Parameters of the cellular immunity and the serum concentration of TNF-α in the group of examined patients were normal. In the group of patients with the cognitive impairments (AMCI + AD), a correlation was found between the number of residual foci of γH2AX and the number of CD3⁺CD4⁺ lymphocytes and the concentration of proinflammatory cytokine TNF-α in the serum. This suggests the development of more pronounced neuroinflammation in patients with reduced ability to repair DNA DSB in this pathology.

中文翻译：

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认知障碍和健康志愿者患者淋巴细胞中DNA双链断裂修复系统的有效性

摘要—

已通过一定剂量的γ射线辐照后残留的γH2AX病灶水平，评估了轻度轻度认知障碍（AMCI）和阿尔茨海默氏病（AD）患者以及健康志愿者的淋巴细胞中DNA DSB修复效率的个体差异。 2 Gy。从被检查患者的外周血中分离出的淋巴细胞在细胞冷冻培养基中冷冻。在研究之前，将冷冻的淋巴细胞融化，悬浮在补充有10％灭活胎牛血清的RPMI 1640培养基中，并分为两半。一半用⁶⁰在4°C下以2 Gy的剂量（0.75 Gy / min的剂量率）在GUT-200M设施上提供共源。然后将对照和辐照的淋巴细胞培养24小时，收集，固定和保存，直到用荧光标记抗体染色后使用荧光显微镜对γH2AX的自发和残留病灶数量进行研究。与健康志愿者相比，在AMCI和АD患者中发现淋巴细胞中残留的γH2AX病灶数量增加，并且包含此类病灶的淋巴细胞数量增加。这表明这些患者中DNA DSB修复的能力降低。所检查的患者组中细胞免疫参数和血清TNF-α的参数均正常。在患有认知障碍（AMCI + AD）的患者组中，⁺ CD4 ⁺淋巴细胞和血清中促炎细胞因子TNF-α的浓度。这表明在这种病理学中，修复DNA DSB的能力下降的患者出现了更为明显的神经炎症。