Abstract
In pathology or under damaging conditions, the properties of cell-free DNA (cfDNA) change. An example of such change is GC enrichment, which drastically alters the biological properties of cfDNA. GC-rich cfDNA is a factor of stress signaling, whereas genomic cfDNA is biologically inactive. GC-rich cfDNA stimulates TLR9-MyD88-NF-κB signaling cascade, leading to an increase in proinflammatory cytokine levels in the organism. In addition, GC-rich DNA is prone to oxidation and oxidized cfDNA can stimulate secondary oxidative stress. This article is a review of works dedicated to the investigation of a low-dose ionizing radiation effect, a bystander effect, and the role of cfDNA in both of these processes.
Highlights
In pathology or under damaging conditions, the properties of cell-free DNA change
CfDNA was studied as a passive marker of cell death in many diseases and conditions such as cancer, autoimmune and cardiovascular diseases, and various types of stress, including radiation-induced [5]. cell-free DNA (cfDNA) is an object for noninvasive diagnostics, including prenatal diagnostics
Tumor cfDNA can be used for early diagnosis, monitoring, and therapeutic prognosis of different types of cancer, including the analysis of the genome of tumor cells as well as for noninvasive detection of pregnancy pathology and disorders of fetal development [6]. cfDNA can be used to assess the risk of damaging factors, including ionizing radiation and ultraviolet radiation [7, 8]. cfDNA is used as a marker of pathology in autoimmune diseases, in acute conditions that lead to death of a large number of cells, sepsis, transplantation, and trauma [9, 10]
Summary
The presence of DNA in the noncellular fraction of peripheral blood (cell-free DNA) was initially identified more than 50 years ago [1]. cfDNA was shown to be present in the blood of healthy subjects. The extracellular telDNA [16] and ribosomal repeat within cfDNA [17] are explored This DNA is, firstly, enriched with GC-rich motifs, including unmethylated CpG motifs, which are recognized by TLR9 receptors and stimulate TLR9-MyD88-NF-kB signaling cascade, activation of which leads to an increase in the concentration of proinflammatory cytokines in the organism. This DNA contains a large count of oxidized and/or oxidizable (dG)n fragments. LDIR can lead to the development of the adaptive response and hormesis, which is of importance when it comes to public health issues [28]
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