Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia.
Institute of High Energy Physics of the National Research Center 'Kurchatov Institute', Protvino, Russia.
Int J Radiat Biol. 2020 Oct;96(10):1245-1253. doi: 10.1080/09553002.2020.1807640. Epub 2020 Aug 25.
The objective of the study was to estimate the DNA damage in blood leukocytes at long terms after irradiation of mice with carbon ions (450 MeV/nucleon) both before and in the Bragg peak.
White outbred SHK male mice were exposed to whole-body irradiation with carbon ions at doses of 0.1-2 Gy in the spread-out Bragg peak and at a dose of 6 Gy before and in the Bragg peak. At different times after irradiation (1-75 days), whole blood was collected from the tail of each mouse and analyzed by the comet assay. Mice X-irradiated in the same dose range served as a positive control. The level of the expression of mRNA of and genes in bone marrow cells was determined in animals irradiated with carbon ions at doses of 0.1-2 Gy using the real-time PCR.
It was found that, 24 h after C-irradiation, a dose-dependent (0.1-2 Gy) increase in the DNA damage of leukocytes occurred, which was accompanied by a decrease in their concentration and an increase in the expression of the and genes in bone marrow cells. The expression of the and genes did not change. In mice C-irradiated at a dose of 6 Gy before and in the Bragg peak, the level of DNA damage changed as follows: by day 3, it increased; by day 23 it returned to the control level; by day 30, it increased again; and by day 75, it fell to the control level on irradiation before the Bragg peak and was significantly higher ( < .05) than in the control after irradiation in the Bragg peak.
The dynamics of changes in the level of DNA damage in leucocytes of C-irradiated mice within 30 days is similar to that in mice exposed to sublethal doses of X-radiation. The retention of the high level of DNA damage by day 75 after C-irradiation in the Bragg peak indicates a significant injury of cells from different cell pools of the blood system. The high level of DNA damage may be related not only to complex DNA injuries but also to chronic oxidative stress.
本研究的目的是估算在碳离子（450 MeV/核子）扩束布拉格峰前后照射下，小鼠血液白细胞中的 DNA 损伤情况。
选用雄性 SHK 白化种系小鼠，全身照射碳离子，剂量范围为 0.1-2 Gy 的扩束布拉格峰内照射和 6 Gy 的布拉格峰前和峰内照射。在照射后不同时间（1-75 天），从每只小鼠的尾巴采集全血，并用彗星试验进行分析。用相同剂量范围的 X 射线照射的小鼠作为阳性对照。用实时 PCR 检测碳离子照射 0.1-2 Gy 剂量的动物骨髓细胞中 和 基因的 mRNA 表达水平。
发现碳离子照射后 24 h，白细胞 DNA 损伤随剂量（0.1-2 Gy）呈依赖性增加，同时白细胞浓度降低，骨髓细胞中 和 基因的表达增加。 和 基因的表达没有改变。在碳离子 6 Gy 的布拉格峰前和峰内照射的小鼠中，DNA 损伤水平的变化如下：第 3 天增加；第 23 天恢复到对照水平；第 30 天再次增加；第 75 天降至布拉格峰前照射的对照水平，且显著高于（ <.05）布拉格峰内照射的对照水平。
在 30 天内，碳离子照射小鼠白细胞中 DNA 损伤水平的变化动态与亚致死剂量 X 射线照射的小鼠相似。在碳离子布拉格峰内照射后 75 天，DNA 损伤保持高水平，表明血液系统不同细胞池的细胞受到严重损伤。高水平的 DNA 损伤可能不仅与复杂的 DNA 损伤有关，还与慢性氧化应激有关。
