11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)

Short-term cell-free DNA changes caused by local electron irradiation of pelvic region in rats

Irina Vasilyeva Alexander Semenov Vladimir Bespalov Sergey Ivanov
Research laboratory of cancer chemoprevention and oncopharmacology, N.N.Petrov National Medical Research Center of Oncology, Saint-Petersburg, Saint-Petersburg, Russia

Radiation pathology is largely determined by the processes of cell death, the one of criterion of which is cell-free DNA (cfDNA).

Objective: To assess the changes of cfDNA after electron radiation of the pelvis and its relation with a number of blood cell count and biochemistry parameters.

The research was performed on 12-week-old female Wistar rats (n=20) weighting 210±35 g. The irradiation of the 2x2 cm pelvic region was carried out on electron accelerator Axesse (Elekta) with an energy of 6 MeV with a dose of 25 Gy. Blood was taken from the peripheral vein at 0, 6, 24 and 48 h after irradiation, and serum was obtained. CfDNA was measured by the ELISA. Blood cell count (WBC, lymphocytes, monocytes and granulocyte) was performed on BC-280Vet (Mindray) analyser. Biochemical analysis (Cholesterol, GGT, Uric acid, Urea, Tryglycerides, Alkaline phosphatase) was performed on Konelab 20 (Thermo Scientific) analyser.

Before irradiation (0h), the level of serum cfDNA was 7.70±0.55 ng/μl, 6h after irradiation it increased to 10.49±0.86 ng/μl (p<0.05), after 24h - to 11.2±1.33 ng/μl (p<0.05) and decreased to control level 48h after irradiation to 8.55±0.73 ng/μl.
WBC decreased from 16.06±1.83×109/L (0h) to 10.57±1.06×109/L (6h) and 10.74±0.99×109/L (24h), lymphocytes from 11.44±1.3×109/L (0h) to 5.84±0.47×109/L (6h), monocytes from 0.51±0.08×109/L (0h) to 0.32±0.03×109/L (6h) and 0.25±0.03×109/L (24h), and granulocytes were stable from 0h (4.11±0.57×109/L) to 6h (4.40±0.70×109/L) but also decreased at 24h (2.14±0.15×109/L).

Serum tryglicerides decreased from 2.05±0.21mmol/l (before irradiation) to 1.41±0.15 mmol/l 24h after (p<0.05). Other parameters didn’t change significantly.

Relative change in cfDNA (0h vs 6h) correlated with tryglyceride changes (0h vs 24h): Tryglycerides=0.32+0.08*cfDNA (R=0.78, p<0.05).

It is possible that the increase in the level of cfDNA already after 6 hours after local irradiation is associated with the development of the pathology, and can predict certain metabolic changes, which allows to accelerate the screening of radioprotective drugs.









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