THE PECULIARITIES OF THE PRODUCTION OF FREE RADICAL COMPOUNDS BY PERIPHERAL BLOOD LYMPHOCYTES AND INTENSITY OF THEIR FORMATION AFTER X-RAY EXPOSURE
DOI:
https://doi.org/10.32471/oncology.2663-7928.t-22-3-2020-g.9096Keywords:
free radical compounds, ionizing radiation, lymphocytes, peripheral bloodAbstract
The problem of assessing the negative effects of ionizing radiation on normal cells and tissues is important for those who are exposed to it due to their profession, cancer patients during chemotherapy and people in radiation-contaminated areas. Its action is mainly realized owing to the direct formation of free radical compounds and indirectly as a result of changes in the intensity of free radical processes in tissues and cells. Aim: to examine in vitro the features of free radical compounds (FRC) production by human lymphocytes of X-ray irradiated blood; to substantiate the use of this indicator as an additional marker for the negative effects of ionizing radiation exposure on humans. Object and methods: in the study, 36 peripheral blood samples from apparently healthy individuals — 18 women aged 39–69 years and 18 men aged 18–58 years — were used. Test X-ray irradiation of blood (TI) was carried out at a dose of 0.5; 1.0; 2.0 and 3.0 Gy. The total intensity of FRC production in peripheral blood lymphocytes was determined with dichloro-fluorescein diacetate fluorescent probe and converted to mmol H2O2 per thousand cells per hour (mmol/thousand cells/hour). Results: in intact lymphocytes, the mean level of FRC production was 21.4 mmol/thousand cells/h and varies from 1.6 to 64.3 mmol/thousand cells/h. The level of FRC production was 1.5 times higher for females than for males. Furthermore, the intensity of FRC production in lymphocytes depended on the age of donors: in the 18–30 years age group it was 1.7 and 2.0 times significantly higher than, respectively, in the 31–50 and 51–69 age groups. After TI, this difference remained despite the dose used. The mean values of FRC production intensity in lymphocytes after TI did not differ from the non-irradiated control. At the same time, when the baseline of FRC production was low (up to 10 mmol/thousand cells/h) TI led to the increase in FRC production by 1.84–2.34 times; when the initial level was high (30 mmol/thousand cells/h and above) TI decreased FRC formation by 1.29–1.35 times. These changes in FRC production were not dose-dependent. At the level of FRC formation from 10 to 30 mmol/thousand cells/h TI did not affect the mean values of this indicator. Conclusions: it is shown that the level of FRC formation in lymphocytes depends on sex and age of the examined people, and the influence of TI on this indicator depends on the initial level of FRC production. The obtained results can provide a basis for the application of FRC formation as a marker in assessing the individual risk of the adverse impact of ionizing radiation exposure in profession activity and radiation therapy.
References
Wilczyńska U, Szeszenia-Dabrowska N. Occupational diseases caused by ionizing radiation in Poland, 1971–2006. Med Pr 2008; 59 (1): 1–8 (in Polish).
Djokovic-Davidovic J, Milovanovic A, Milovanovic J, et al. Analysis of chromosomal aberrations frequency, haematological parameters and received doses by nuclear medicine professionals. J BUON 2016; 21 (5):1307–15.
Gerić M, Popić J, Gajski G, et al. Cytogenetic status of interventional radiology unit workers occupationally exposed to low-dose ionising radiation: A pilot study. Mutat Res 2019; 843: 46–51.
Loganovsky KN, Marazziti D, Fedirko PA, et al. Radiation-Induced Cerebro-Ophthalmic Effects in Humans. Life (Basel) 2020; 10 (4): 41.
Ahmad IM, Abdalla MY, Moore TA, et al. Healthcare Workers Occupationally Exposed to Ionizing Radiation Exhibit Altered Levels of Inflammatory Cytokines and Redox Parameters. Antioxidants (Basel) 2019; 8 (1): 12.
Domina EA. Evaluation of the effect of professional irradiation on cytogenetic parameters of peripheral blood lymphocytes. Dopov Nac akad nauk Ukr 2018; 10: 112–9 (in Russian).
Domina EA. Radiogenic cancer: epidemiology and primary prevention. Kiev: Naukova Dumka, 2016. 195 p. (in Russian).
Yahyapour R, Motevaseli E, Rezaeyan A, et al. Reduction-oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics. Clin Transl Oncol 2018; 20 (8): 975–88.
Wason MS, Lu H, Yu L, et al. Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer to Radiation Therapy through Oxidative Activation of the JNK Apoptotic Pathway. Cancers (Basel) 2018; 10 (9): 303.
Ping Z, Peng Y, Lang H, et al. Oxidative Stress in Radiation-Induced Cardiotoxicity. Review Oxid Med Cell Longev 2020; V. 2020, Art. ID 3579143, 15 p.
Franco A, Ciccarelli M, Sorriento D, et al. Rays Sting: The Acute Cellular Effects of Ionizing Radiation Exposure. Transl Med UniSa 2016; 14 (8): 42–53.
Choi KM, Kang CM, Cho ES, et al. Ionizing radiation-induced micronucleus formation is mediated by reactive oxygen species that are produced in a manner dependent on mitochondria, Nox1, and JNK. Oncol Rep 2007; 17 (5):1183–8.
Pereboeva L, Westin E, Patel T, et al. DNA damage responses and oxidative stress in dyskeratosis congenital. PLoS One 2013; 8 (10): e76473.
Kawamura K, Qi F, Kobayashi J. Potential relationship between the biological effects of low-dose irradiation and mitochondrial ROS production. J Radiat Res 2018; 59 (Suppl. 2): ii91-ii97.
Sangsuwan T, Haghdoost S. The nucleotide pool, a target for low-dose gamma-ray-induced oxidative stress. Radiat Res 2008; 170 (6): 776–83.
Farhood B, Ashrafizadeh M, Khodamoradi E, et al. Targeting of cellular redox metabolism for mitigation of radiation injury. Life Sci 2020; 250:117570.
Domina EA. Radiogenic cancer: Epidemiology and primary prevention. Kiyv: Naukova Dumka, 2016. 196 p. (in Russian).
Grinevich YuA, Domina EA. Immune and cytogenetic effects of dense and rarely ionizing radiation. Kiev: Zdorov’ya, 2006. 200 p. (in Russian).
Ogawa Y, Kobayashi T, Nishioka A, et al. Radiation-induced reactive oxygen species formation prior to oxidative DNA damage in human peripheral T cells. Int J Mol Med 2003; 11 (2): 149–52.
Tang Y, Zhang Y, Guo L, et al. Relationship between individual radiosensitivity and radiation encephalopathy of nasopharyngeal carcinoma after radiotherapy. Strahlenther Onkol 2008; 184 (10): 510–4.
Borgmann K, Hoeller U, Nowack S, et al. Individual radiosensitivity measured with lymphocytes may predict the risk of acute reaction after radiotherapy. Int J Radiat Oncol Biol Phys 2008; 71 (1): 256–64.
Guogytė K, Plieskienė A, Ladygienė R, et al. Assessment of Correlation between Chromosomal Radiosensitivity of Peripheral Blood Lymphocytes after In vitro Irradiation and Normal Tissue Side Effects for Cancer Patients Undergoing Radiotherapy. Genome Integr 2017; 8: 1.
Adamczyk A, Biesaga B, Klimek M, et al. Comet assay is not useful to predict normal tissue response after radiochemotherapy in cervical and larynx cancer patients Pol J Pathol 2018; 69 (4): 410–21.
Pajic J, Rovcanin B, Kekic D, et al. The influence of redox status on inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation. Int J Radiat Biol 2018; 94 (6): 569–75.
Product Information Histopaque®-1077 Hybri-Max™ (H8889) (https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma/Product_Information_Sheet/2/h8889pis.pdf).
Bokunyaeva NI, Zolotnitskaya RP. Handbook of clinical laboratory research methods. Moscow: Meditsina, 1975. 338 р. (in Russian).
Yao K, Wu W, Wang K, et al. Electromagnetic noise inhibits radiofrequency radiation-induced DNA damage and reactive oxygen species increase in human lens epithelial cells. Mol Vis 2008; 19 (14): 964‑9.
Tarpey MM, Wink DA, Grisham MB. Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations. Am J Physiol Regul Integr Comp Physiol 2004; 286: R431–44.
Lakin GF. Biometry. Moskow: Vyschaya Shkola, 1990. 352 p. (in Russian).
Song Y, Xie L, Lee Y, et al. Integrative assessment of low-dose gamma radiation effects on Daphnia magna reproduction: Toxicity pathway assembly and AOP development. Sci Total Environ 2020; 705: 135912.
Gomes T, Song Y, Brede DA, et al. Gamma radiation induces dose-dependent oxidative stress and transcriptional alterations in the freshwater crustacean daphnia magna. Sci. Total Environ 2018; (628–629): 206–16.
Hoeller U, Borgmann K, Bonacker M, et al. Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer. Radiother Oncol 2003; 69 (2): 137–44.
