Blinova E A, Nikiforov V S, Yanishevskaya M A, Akleyev A А
Urals Research Center for Radiation Medicine, Chelyabinsk, Russia Chelyabinsk State University, Chelyabinsk, Russia.
Urals Research Center for Radiation Medicine, Chelyabinsk, Russia.
Vavilovskii Zhurnal Genet Selektsii. 2020 Jul;24(4):399-406. doi: 10.18699/VJ20.632.
It is known that ionizing radiation influences the expression of the genes that play a key role in the mechanisms of maintaining the stability of cellular homeostasis. As a rule, changes in the transcriptome of an exposed cell occur within the first 24 hours following radiation exposure. And it predetermines early response in the case of genome damage. Later on modulations in gene transcription activity are also possible and could result in a carcinogenic effect. However, in order to find the role of exogenous factors (ionizing radiation), it is also necessary to take into account the contribution of endogenous factors that are able to modify gene transcription activity. This is especially important for long after the onset of radiation exposure. Single nucleotide polymorphisms located in regulatory regions of the genes may belong to this group of factors. The objective of the current study was to analyze the influence of ionizing radiation on the transcription activity of the STAT3, GATA3, NFkB1, PADI4 genes, which regulate proliferation and differentiation of immune competent human cells; and to assess the potential influence of single nucleotide polymorphisms located in regulatory regions of the genes on the amount of mRNA. The study involved people who had been chronically exposed due to releases of radioactive waste into the Techa River. It was observed that 60 years after the onset of radiation exposure changes in the transcription activity of the NFkB1 and PADI4 genes were registered in people with cumulative doses to RBM within the range 78-3510 mGy. In people who had been chronically exposed, the effect of allelic variations in rs1053023, rs4143094, rs28362491, rs874881 on the level of mRNAs of the STAT3, GATA3, PADI4, NFkB1 genes has not been established.
众所周知,电离辐射会影响在维持细胞内稳态稳定性机制中起关键作用的基因的表达。通常,受照射细胞的转录组变化发生在辐射暴露后的头24小时内。这预先决定了基因组受损情况下的早期反应。随后基因转录活性也可能发生调节,并可能导致致癌作用。然而,为了确定外源性因素(电离辐射)的作用,还必须考虑能够改变基因转录活性的内源性因素的作用。这在辐射暴露开始很久之后尤为重要。位于基因调控区域的单核苷酸多态性可能属于这组因素。本研究的目的是分析电离辐射对调节人类免疫活性细胞增殖和分化的STAT3、GATA3、NFkB1、PADI4基因转录活性的影响;并评估位于基因调控区域的单核苷酸多态性对mRNA量的潜在影响。该研究涉及因放射性废物排放到捷恰河而长期受照射的人群。观察到,在辐射暴露开始60年后,累积剂量到红骨髓在78 - 3510 mGy范围内的人群中,NFkB1和PADI4基因的转录活性发生了变化。在长期受照射的人群中,rs1053023、rs4143094、rs28362491、rs874881等位基因变异对STAT3、GATA3、PADI4、NFkB1基因mRNA水平的影响尚未确定。