Korzeneva Inna B, Kostuyk Svetlana V, Ershova Elizaveta S, Skorodumova Elena N, Zhuravleva Veronika F, Pankratova Galina V, Volkova Irina V, Stepanova Elena V, Porokhovnik Lev N, Veiko Natalia N
Russian Federal Nuclear Center - All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190 Sarov, 37 Mira ave., Nizhniy Novgorod Region, Russia.
Research Centre for Medical Genetics, 115478 Moscow, 1 Moskvorechye str., Russia.
Mutat Res. 2016 Sep-Oct;791-792:49-60. doi: 10.1016/j.mrfmmm.2016.09.001. Epub 2016 Sep 7.
A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N=88) and tritium β-radiation (N=88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the circulating cfDNA as compared with the cfDNA of non-exposed people (N=109). Such index that simultaneously displays both the increase of rDNA content and decrease of satellite III content in the cfDNA (RrDNA/RsatIII) can be recommended as a marker of chronic processes in the body that involve the elevated cell death rate and/or increased blood plasma endonuclease activity.
单次暴露于电离辐射(IR)会导致血浆中游离DNA(cfDNA)含量升高。在这种情况下,cfDNA浓度可作为机体细胞死亡的标志物。然而,长期低剂量暴露于IR会增强血浆中的核酸内切酶活性以及抗DNA抗体滴度,导致受照射人群循环cfDNA的总浓度降低。在这种情况下,总cfDNA浓度不应被视为受照射机体细胞死亡的标志物。我们假设,受照射人群中循环的cfDNA池包含在血浆核酸内切酶活性升高的环境中对双链断裂形成具有抗性的DNA片段,并且可以在血浆中积累。为了验证这一假设,我们研究了从285名个体获得的cfDNA样本中人类核糖体重复序列(rDNA)转录区域富含GC的序列(69%GC)的含量,以及卫星III(1q12)富含AT的重复序列(63%AT)的含量。我们发现,与未受照射人群(N = 109)的cfDNA相比,长期暴露于γ - 中子辐射(N = 88)和氚β辐射(N = 88)会导致循环cfDNA中rDNA含量增加(RrDNA指数)以及卫星III含量降低(RsatIII指数)。这种同时显示cfDNA中rDNA含量增加和卫星III含量降低的指数(RrDNA/RsatIII)可被推荐作为体内涉及细胞死亡率升高和/或血浆核酸内切酶活性增加的慢性过程的标志物。