Abstract—
The study was designed to identify an index that changes shortly after irradiation and can be used for early (within 6–24 h) diagnosis of the initiation of cystitis as a complication arising during radiation therapy of patients with malignant neoplasms in the pelvic organs. Our newly developed model of radiation-induced cystitis is based on a single irradiation of the urinary bladder area in rats on a linear electron accelerator Axesse (Elekta, Sweden) with a quantum energy of 6 MeV at a dose of 25 Gy at a dose rate of 4.50 Gy/min. Early effects were estimated by a change in the total number of leukocytes and their fractions, the concentration of extracellular DNA (exDNA), and the cholesterol, gamma-glutamyl transferase, urea, and alkaline phosphatase of the serum in the peripheral blood in 6 and 24 h after irradiation. Within 6 h after the effect, a decrease in the total number of leukocytes, lymphocytes, and monocytes was observed (from 16.06 ± 1.83 to 10.57 ± 1.06; from 11.44 ± 1.30 to 5.84 ± 0.47; and from 0.51 ± 0.08 to 0.32 ± 0.03 (×109/L), respectively), while 24 h later, the number of granulocytes also decreased from 4.11 ± 0.57 to 2.14 ± 0.15 (×109/L). In 6 and 24 h after irradiation, there was an increase in the concentration of exDNA in the blood serum from 7.70 ± 0.55 to 11.20 ± 1.33 ng/μL normalized by 48 h after the effect. ExDNA is an index of cell death with a local effect of radiation and can be a promising early noninvasive marker of the development of radiation cystitis, which will probably be important in the choice of means for the prevention of the occurrence of radiation pathology.
REFERENCES
Villeirs, L., Tailly, Th., Ost, P., et al., Hyperbaric oxygen therapy for radiation cystitis after pelvic radiotherapy: systematic review of the recent literature, Int. J. Urol., 2020, vol. 2, pp. 98–107.
Oscarsson, N., Müller, B., Rosen, A., et al., Radiation-induced cystitis treared with hyperbaric oxygen therapy (RICH-ART): a randomized, controlled, phase 2–3 trial, Lancet Oncol., 2019, vol. 11, pp. 1602–1614.
Zwaans, B.M.M., Lamb, L.E., Bartolone, S., Nicolai, H.E., et al., Cancer survivorship issues with radiation and hemorrhagic cystitis in gynecological malignancies, Int. Urol. Nephrol., 2018, vol. 10, pp. 1745–1751.
Vasilyeva, I.N., Bespalov, V.G., Von, J.D., et al., Cell-free DNA plasma levels differ in age-specific pattern in healthy rats and castrated with testosterone-induced benign prostatic hyperplasia, Int. J. Genomics, 2019, p. 8173630.
Lee, A.Y., Golden, D.W., Bazan, J.G., et al., Hematologic nadirs during chemoradiation for anal cancer: temporal characterization and dosimetric predictors, Int. J. Radiat. Oncol. Biol. Phys., 2017, vol. 97, no. 2, pp. 306–312.
Sanguineti, G., Giannarelli, D., Petrongari, M.G., et al., Leukotoxicity after moderately hypofractionated radiotherapy versus conventionally fractionated dose escalated radiotherapy for localized prostate cancer: a secondary analysis from a randomized study, Radiat. Oncol., 2019, vol. 14, no. 23.
Mohamed, N.E. and Ashour, S.E., Role of ethanolic extract of Morus alba leaves on some biochemical and haematological alterations in irradiated male rats, Int. J. Radiat. Biol., 2018, vol. 94, no. 4, pp. 374–384.
Vasilyeva, I.N. and Bespalov, V.G., Release of extracellular DNA after administration of radioprotective combination of α-tocopherol and ascorbic acid, Radiats. Biol. Radioecol., 2015, vol. 55, no. 5, pp. 495–500.
Vasilyeva, I.N., Podgornaya, O.I., and Bespalov, V.G., Nucleosome fraction of extracellular DNA as the index of apoptosis, Tsitologiya, 2015, vol. 57, no. 2, pp. 87–94.
Moss, J., Magenheim, J., Neiman, D., et al., Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease, Nat. Commun., 2018, vol. 9, p. 5068.
Snyder, M.W., Kircher, M., Hill, A.J., et al., Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin, Cell, 2016, vol. 164, nos. 1–2, pp. 57–68.
Ashry, O.M., Hussein, E.M., and Abd El-Azime, A.Sh., Restorative role of persimmon leaf (Diospyros kaki) to gamma irradiation induced oxidative stress and tissue injury in rats, Int. J. Radiat. Biol., 2017, vol. 93, no. 3, pp. 324–329.
Liu, J., Au, YengSh.L., Kwok, M.K., et al., The effect of liver enzyme on bone composition: a Mendelian randomization study, PLoS One, 2020, vol. 15, no. 2, p. e0228737.
Lenarczyk, M., Kronenberg, A., Mader, M., et al., Age of exposure to radiation determined severity of renal and cardiac disease in rats, Radiat. Res., 2019, vol. 192, no. 1, pp. 63–67.
Korytov, O.V., Korytova, L.I., Ponezha, T.E., et al., Method for modeling radiation cystitis, RF Patent no. 2676431, 2018.
Korytov, O.V., Korytova, L.I., Akhmetzyanov, A.R., et al., Experimental models of radiation-induced cystitis in laboratory animals, Vopr. Onkol., 2019, vol. 65, no. 3, pp. 337–341.
Ocana, A., Nieto-Jiménez, C., Pandiella, A., and Templeton, A.J., Neutrophils in cancer: prognostic role and therapeutic strategies, Mol. Cancer, 2017, vol. 16, no. 1, pp. 137–143.
Guner, A. and Kim, H.I., Biomarkers for evaluating the inflammation status in patients with cancer, J. Gastric Cancer, 2019, vol. 19, no. 3, pp. 254–277.
Brengues, M., Lapierre, A., Bourgier, C., et al., T lymphocytes to predict radiation-induced late effects in normal tissues, Exp. Rev. Mol. Diagn., 2017, vol. 17, no. 2, pp. 119–127.
Holdenrieder, S. and Stiber, P., Clinical use of circulating nucleosomes, Crit. Rev. Clin. Lab. Sci., 2009, vol. 46, no. 1, pp. 1–24.
Fehr, Y., Holdenrieder, S., Hoffman, R.-Th., et al., Circulating nucleosomes in cancer patients with liver matastases undergoing selective internal radiation therapy using Yttrium-90 labelled microspheres, in Circulating Nucleic Acids in Plasma and Serum, Gahan, P.B., Ed., Dordrecht: Springer, 2009, pp. 91–96.
Holdenrieder, S., Liquid profiling of circulating nucleic acids as a novel tool for the management of cancer patients, Adv. Exp. Med. Biol., 2016, vol. 924, pp. 53–60.
Ermakov, A.V., Kon’kova, M.S., Kostyuk, S.V., and Veiko, N.N., DNA-signaling pathway mediating development of a radiation induced bystander effect in human cells, Radiats. Biol., Radioekol., 2011, vol. 51, no. 6, pp. 651–659.
Chernikov, A.B., Gudkov, S.V., Usacheva, A.M., and Bruskov, V.I., Exogenous 8-oxo-7,8-dihydro-2'-deoxyguanosine: biomedical properties, mechanisms of action, and therapeutic potential, Usp. Biol. Khim., 2017, vol. 57, pp. 267–302.
Kostyuk, S.V., Ermakov, A.V., Alekseeva, A.Yu., et al., Role of extracellular DNA oxidative modification in radiation induced bystander effects in human endotheliocytes, Mutat. Res., 2012, vol. 729, nos. 1–2, pp. 52–60.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest. The authors declare that they have no conflicts of interest.
Statement on the welfare of animals. This work was carried out according to the requirements of current standards for the maintenance and use of laboratory animals.
Additional information
Translated by A. Barkhash
Rights and permissions
About this article
Cite this article
Vasilyeva, I.N., Korytov, O.V., Ivanov, S.D. et al. Changes in the Concentration of Extracellular DNA and Peripheral Blood Leukocytes in the Early Stages of Development of Radiation Cystitis in Rats. Biol Bull Russ Acad Sci 49, 2279–2284 (2022). https://doi.org/10.1134/S106235902212024X
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S106235902212024X