EXPERIENCE OF PRECLINICAL AND CLINICAL STUDY OF EXTRACELLULAR DNA IN VARIOUS PATHOLOGIES

DOI: https://doi.org/10.29296/25877313-2019-10-08
Issue: 
10
Year: 
2019

I.N. Vasilyeva Ph.D. (Biol.), Senior Research Scientist, Laboratory of Cancer Chemoprevention and Oncopharmacology, N.N. Petrov National Medical Research Center of Oncology E-mail: iravasilyeva@hotmail.com V.G. Bespalov Dr.Sc. (Med.), Head of Laboratory of Cancer Chemoprevention and Oncopharmacology, N.N. Petrov National Medical Research Center of Oncology A.L. Semenov Research Scientist, Laboratory of Cancer Chemoprevention and Oncopharmacology, N.N. Petrov National Medical Research Center of Oncology G.V. Tochilnikov Ph.D. (Med.), Research Scientist, Laboratory of Cancer Chemoprevention and Oncopharmacology, N.N. Petrov National Medical Research Center of Oncology

Our experimental and clinical studies revealed changes in the content of extracellular DNA (exDNA) in the blood plasma for various pathologies. Ionizing irradiation of rats causes an increase in the content of nucleosomal exDNA in proportion to the radiation dose. Sequencing of exDNA of the irradiated rats shows that this exDNA is released from various parts of the genome and various tissues. Low-frequency noise in single or repeated exposure leads to increase in the content of exDNA, significantly greater in chronic acoustical exposure. Consequently, ionizing radiation and low-frequency noise increase the apoptosis of cells. Administering to rats a combination of vitamins A and E before irradiation raises the level of exDNA, this pro-apoptotic effect of vitamins explains their radioprotective effect as a result of the death of damaged cells. The exDNA level is significantly increased in old intact male rats in comparison with young male rats; exDNA level does not change with testosterone induction of benign hyperplasia of the prostate (BPH) in the young rats, whereas in the old rats increases significantly, which indicates the intensification of apoptosis processes with age and with the development of BPH in old animals. The content of exDNA is increased within 3 days after an acute period in patients with acute impairment of cerebral circulation, and dynamics of change of exDNA levels in patients with ischemic and hemorrhagic stroke is different, which can be used both: to assess the severity of brain damage, and for differential diagnosis of various types of strokes. In patients with COPD the content of exDNA decreases during remission, which indicates the reduction of cell death in the lungs and the reduction of inflammatory process. Thus, the finding of exDNA in blood plasma can be used for the diagnosis of various pathologies, monitoring and evaluating the effectiveness of treatment.

Keywords: 
extracellular DNA
nucleosomes
apoptosis
pathologies

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