INTENSITY OF OXIDATIVE PROCESSES IN BLOOD AND LEVEL OF APOPTOSIS IN BLOOD LYMPHOCYTES IN RADIOLOGISTS/X-RAY TECHNOLOGIES EXPOSED TO SMALL DOSES OF IONIZING RADIATION. / ІНТЕНСИВНІСТЬ ОКИСНИХ ПРОЦЕСІВ В КРОВІ ТА РІВЕНЬ АПОПТОЗУ В ЛІМФОЦИТАХ КРОВІ У РАДІОЛОГІВ/РЕНТГЕНОЛОГІВ, ЯКІ ЗАЗНАЮТЬ ВПЛИВУ МАЛИХ ДОЗ ІОНІЗУЮЧОГО ВИПРОМІНЮВАННЯ.

OBJECTIVE: to determine the presence of changes in peripheral blood parameters, characterizing its redox state, and the level of apoptosis of lymphocyte in radiologists/x-ray technologies who, due to their official duties, are exposed to small doses of ionizing radiation. OBJECT AND METHODS: The work was performed on blood samples of 45 professionals radiologists/x-ray technologies and 52 conventionally healthy individuals (control group). The content of malondialdehyde and sulfhydryl groups of proteins and peptides (-SH) in blood plasma was determined; catalase enzyme activity and the ratio of pro-antioxidant processes in hemolysates, the level of superoxide anion-radical (О2-) generation, the total production offree radical compounds (reactive forms of oxygen and nitrogen) and the level of apoptosis of peripheral blood lymphocytes (PBL). RESULTS: The content of malondialdehyde in the blood of professionals was increased by 1.49 times and the contentof -SH was decreased by 1.67 times compared to conventionally healthy individuals. An increase in the level of О2-production by 1.56 times was observed for PBL. The obtained results indicate a shift in the ratio between antioxidant and pro-oxidant processes towards the latter, which is confirmed by a 1.49-fold increase of this index. The levelfor PBL apoptosis was reduced by 1.35 times. For professionals, against the background of increased generation of О2-, a reliable direct correlation was observed between the indicator of apoptosis and the total production of free radical compounds, and between the latter and the level of apoptosis of lymphocytes, which was not noted for the conventionally healthy individuals group. CONCLUSION: A change in the ratio between pro- and antioxidant processes in the blood was found for professionals who are in contact with sources of ionizing radiation, which indicates the possibility of the development of oxidative stress, and the consequence of a reduced level of apoptosis of lymphocytes may be the danger of accumulating genetic damage in these cells.

RELEVANT BIOCHEMICAL INDICES OF BLOOD RADIOSENSITIVITY IN GYNECOLOGICAL CANCER PATIENTS. / RELEVANTNI BIOKhIMIChNI POKAZNYKY RADIOChUTLYVOSTI KROVI ONKOGINEKOLOGIChNYKh KhVORYKh.

OBJECTIVE: identification of the relevant biochemical indices of blood radiosensitivity in endometrial cancerpatients under the test irradiation in a wide range of doses. MATERIALS AND METHODS: Peripheral blood samples were drawn for assay in the newly diagnosed endometrial cancer patients (study group, n = 42) and healthy donors (control group, n = 27). A set of biochemical values was reviewed to identify and justify the prognostic markers of cell radiosensitivity in the tumor environment featuring gradual development of oxidative stress, namely the intensity of superoxide anionradical (О2) generation, pro/antioxidant ratio (PAR), and malondialdehyde (MDA) content. Predictive values were selected through the construction and analysis of «doseresponse¼ dependencies of the studied parameters during Xray test exposure in a dose range of 0.5-3.0 Gy. Nature of the dose curves was determined using linear and linearquadratic regression models. RESULTS: The 3.2 times higher MDA content was found in blood plasma of endometrial cancer patients compared to the control group, namely (60.87 ± 4.93) µM/g of protein versus (18.93 ± 2.05) µM/g of protein (р ≤ 0.05). The raise in MDA content along with increase in the test radiation dose (in a range of 0.5-3.0 Gy) was approximated by the linear regression model Y = 67.44 + 12.52D, R2 = 0.85. A 1.29-1.74fold increase in the mean group value depending on the radiation dose was recorded (р ≤ 0.05). Effects of lowdose irradiation (0.5 Gy) were differentiated as (85.03 ± 8.9) against the initial MDA level of (60.87 ± 4.93) µM/g of protein. There was an increase in the intensity of О2 generation in blood lymphocytes and elevated PAR value in hemolysate from endometrial cancer patients compared to healthy donors by 1.34 and 1.30 times (р ≤ 0.05) respectively, which indicated the intensification of prooxidant processes in patients. The interindividual peculiarities of the blood reactionresponse to radiation were revealed according to parameters depending on the initial values, which characterize them only as additional prognostic biomarkers in radiation treatment planning for gynecological cancer patients. CONCLUSIONS: It has been proven that the linear nature of dose dependence of MDA content in blood plasma of endometrial cancer patients and response to lowdose irradiation of are the basic criteria for recognizing MDA as a relevant prognostic biochemical indicator of radiosensitivity of healthy cells from the tumor environment. The content of MDA in blood plasma of gynecological cancer patients should be taken into account in order to identify the subjects with a high risk of radiation complications.

Disordered redox metabolism of brain cells in rats exposed to low doses of ionizing radiation or UHF electromagnetic radiation.

AIM: To investigate the changes of redox-state of mammalian brain cells as the critical factor of initiation and formation of radiation damage of biological structures in setting of continuous exposure to low doses of ionizing radiation or fractionated ultra high frequency electromagnetic radiation (UHF EMR) at non-thermal levels. MATERIALS AND METHODS: The influence of low-intensity ionizing radiation was studied on outbred female rats kept for 1.5 years in the Chernobyl accident zone. The effects of total EMR in the UHF band of non-thermal spectrum were investigated on Wistar rats. The rate of formation of superoxide radicals and the rate of NO synthesis in mitochondria were determined by the EPR. RESULTS: After exposure to ionizing or UHF radiation, the levels of ubisemiquinone in brain tissue of rats decreased by 3 and 1.8 times, respectively. The content of NO-FeS-protein complexes in both groups increased significantly (р < 0.05). In the conditions of ionizing or EMR the rates of superoxide radical generation in electron-transport chain of brain cell mitochondria increased by 1.5- and 2-fold, respectively (р < 0.05). In brain tissue of rats kept in the Chernobyl zone, significant increase of NO content was registered; similar effect was observed in rats treated with UHFR (р < 0.05). CONCLUSIONS: The detected changes in the electron transport chain of mitochondria of brain cells upon low-intensity irradiation or UHF EMR cause the metabolic reprogramming of cell mitochondria that increases the rate of superoxide radical generation and nitric oxide, which may initiate the development of neurodegenerative diseases and cancer. This article is part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

Fractionate effect of ionizing radiation and nitric oxide on tumor growth in rats. / Frakcionirovannoe dejstvie ioniziruyushhix izluchenij i oksidov azota na rost opuxolej u krys.

Objective. To investigate the effect of ionizing radiation and nitrogen oxides on the growth and development of Guerin's carcinoma transplanted in rats. Materials and methods. Studies have been conducted on white nonlinear male rats weighing 125-160 g. Animals were exposed of nitrogen oxides and/or ionizing radiation, and then were transplanted Guerin's carcinoma. The dynamics of tumor growth and changes of free radical processes in the blood system by biophysical and biochemical methods were investigated. Results. It is shown that the effect of the studied environmental factors leads to disruption of oxidative processes in the animal's organism, which contributes to the growth and development of tumors. Conclusion. Pre-exposure to low doses of ionizing radiation and/or exogenous nitrogen oxides significantly accelerates the growth of Guerin's carcinoma. This process is accompanied by a disturbance of oxidative metabolism and the development of oxidative stress.

Fractionated low-dose radiation exposure potentiates proliferation of implanted tumor cells.

AIM: The purpose of this study is to test whether whole-body fractionated exposure of tumor-free animals to low doses of low-LET radiation (at the total delivered dose of 1.0 Gy of X-rays) is capable of potentiating growth of subsequently implanted tumor cells. MATERIALS AND METHODS: Adult male rats were fractionally exposed to low doses of X-rays (10 acute exposures with 0.1 Gy each and with a frequency of 1 exposure per 3 days). The next day after the last irradiation rats were implanted with Guerin carcinoma (GC) cells. On the 12th and 18th days after implantation of GC cells, animals were sacrificed, and the mass of tumors was measured by weighing them, although the kinetics of tumor growth was also examined by daily measurements of the dimensions of tumors. Cytotoxic effects in the bone marrow were assessed flow cytometrically in acridine orange-stained unfractionated bone marrow cells using the ratio of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE). RESULTS: In irradiated rats, tumors grew apparently faster than in unirradiated rats for up to 18 days after implantation of GC cells. On the 18th day after implantation of GC cells the average value of the mass of tumors in irradiated rats was 2.8-fold higher compared with the average value of the mass of tumors in unirradiated rats (p < 0.05). On this day post-implantation, the bone marrow in irradiated animals was 1.8-fold more suppressed (as evidenced by decreased PCE/NCE ratios) than that in animals that were irradiated, but were not implanted with GC cells (p > 0.05), and was 1.4-fold more suppressed than that in animals that were not irradiated, but were implanted with GC cells (p > 0.05). CONCLUSION: Fractionated irradiation of tumor-free animals with low doses of X-rays potentiates proliferation of subsequently implanted GC cells. This potentiation seems to be associated with radiation-induced impaired hematopoiesis.

[Genotoxic effects of radiation and hyperthermia in inbred mice strains with different radiation sensitivity].

Peculiarities of repair of DNA injuries induced by radiation and hyperthermia and their realization on chromosomal level in bone marrow cells ofexperimental animals with different radiation sensitivity were studied. It is shown that radiomodification efficiency of mild hyperthermia is higher for radioresistant animals. More intensive elimination of chromosomal injuries the level of which in remote terms of examination corresponds to the control value, is observed. In the group of animals with higher radiation sensitivity prolonged thermal potentiation of radiation effects on chromosomal level is determined.

[Non-specific stress-reaction as indicator of radiosensitivity].

The data presented demonstrate possible personal radiosensitivity prognosis according to the immobilization stress response (animal model). It was demonstrated on the Wistar rats that in radiosensitive animals initial oxidative metabolism parameters were higher than in radioresistant ones, and prooxidant-antioxidant balance alteration after non-radiation stress were more evident and kept for a longer period. Those animals had had limphopenia and neutrophilosis. The differences in the response types between radiosensitive and radioresistant animals were due to the blood system reserve abilities, as well as the state of natural mature cells depot, and antioxidant defence enzymes.