It has been established that cell-free DNA (cfDNA) circulates throughout the bloodstream, affecting cells. The characteristics of cfDNA depend on the physiological state of the organism. Diseases can cause GC-enrichment of the cfDNA pool (cerebral atherosclerosis, heart attack, rheumatic arthritis, cancer). As was shown previously, cfDNA pool is enriched with ribosomal GC repeat in cases of people working with gamma-radiation (N=230).
GC-rich cfDNA causes adaptive response in human adipose-derived mesenchymal stem cells (MSCs) via DNA damage response. It rapidly induces DNA breaks after 30 minutes of incubation (shown by means of single cell electrophoresis and flow cytometry), leading to increase in DNA reparation gene level BRCA1 (6,5-fold) and anti-apoptotic genes BCL2 (4,5 - fold), BCL2A1 (5-fold), BCL2L1 (3-fold), BIRC3 (5-fold), BIRC2(6-fold) after 3 hours of incubation. Moreover, GC-rich DNA activates NF-kB signaling pathway: NF-kB translocates to the nucleus after 1 h of incubation (fluorescent microscopy) and genes of NF-kB signaling pathway: MAP3K1, MAP4K4, NFKB1A, REL, IKBKB, RelA (p65), NFRKB, NFKB1 and NFKB2 increase 2 – 5,5-fold (RT-PCR). Expression of NF-kB target proinflammatory cytokines genes TNFa (3,9-fold), IL1B (2,4-fold), IL8 (2,8-fold), IL6 (1,7-fold), TNFRSF1A (3,2-fold) increases. In addition, level of apoptosis decreases and proliferation rises, level of Ki-67 and PCNA proteins increases (flow cytometry). Treating MSCs with GC-rich cfDNA prior to exposure to damaging factors such as ionizing radiation positively affects cell survival - radiation induces less DNA breaks and less cell death in cell cultures treated with GC-rich cfDNA.
Conclusion. GC-rich fragments of the ribosomal repeat in the pool of cfDNA can be inductors of adaptive response development in cases of exposure to external damaging factors (ex. ionizing radiation).