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.

FEATURES OF OXIDATIVE METABOLISM AND GENETIC DISORDERS IN PERIPHERAL BLOOD LYMPHOCYTES OF PATIENTS WITH PRIMARY CERVICAL CANCER.

BACKGROUND: The combination of chemo- and radiotherapy used as main treatment of locally advanced cervical cancer (CC) may lead to side effects in healthy cells, which undermine the effectiveness of treatment and quality of life. The assessment of damage level in healthy radiosensitive cells from the tumor environment before the treatment is important in order to predict and prevent remote side effects of radiation. AIM: To study the oxidative metabolism and genetic disorders in peripheral blood lymphocytes (PBL) of primary CC patients in order to evaluate the possibilities of predicting radiation complications based on the molecular and biological properties of PBL. MATERIALS AND METHODS: Peripheral blood samples were collected from 13 primary CC patients T1-4N0-1M0-1, and PBL were routinely isolated. The oxidative metabolism (mitochondrial trans-membrane potential, superoxide anion radical (О2•) generation, reactive oxygen species (ROS) production in PBL as well as the level of SH-groups in plasma and pro/antioxidant ratio in hemolysates were examined. The development of genetic instability was determined by estimation of DNA double-strand breaks (DNA-DSB), frequency and spectrum of chromosome aberrations and apoptosis. RESULTS: The marked increase in the intensity of О2• generation in PBL (1.5-fold), depletion of SH-groups content (1.6-fold) and a shift in the pro-antioxidant balance (1.4-fold) towards its prooxidant component were observed in the blood of primary CC patients as compared to healthy individuals. These oxidative stress related events were accompanied by an increase in the level of DNA-DSB (2.1-fold), apoptosis (3.5-fold) and frequency of cells with chromosome aberrations (3.9-fold). On the contrary, significant decrease in mitochondrial trans-membrane potential (2.0-fold) and ROS generation in PBL (4.0-fold) were detected. CONCLUSION: Preliminary data indicate a violation of redox processes regulation, a shift in the pro-antioxidant balance towards its pro-oxidant component, accompanied by an increase in the level of DNA damage, development of genetic instability and apoptotic death of blood lymphocytes in primary CC patients.

Effects of brachytherapy on cytogenetic parameters and oxidative status in peripheral blood lymphocytes of gynecologic cancer patients.

BACKGROUND: The state-of-the-art brachytherapy technologies with high-dose sources of 60Co and 192Ir within contemporary treatment protocols for cancer patients allow achieving maximum dose distribution in the clinical target and with minimum radiation exposure of surrounding organs and tissues. For minimization and overcoming the early and late radiation complications, development of respective radiobiological criteria along with perfecting of physical and technical characteristics of the ionizing radiation sources are required. AIM: To study the effect of 192Ir radiation on the chromosomal aberrations and prooxidant/antioxidant status of blood lymphocytes in gynecological cancer patients. MATERIALS AND METHODS: The patients (n = 45) with endometrial, cervical and secondary cancer of vagina were enrolled in the study. For brachytherapy, the irradiation of vaginal mucosa was conducted using "GammaMed plus" device for contact radiation therapy with 192Ir source. Prior to irradiation and in 20-24 h after brachytherapy session, the venous blood samples were obtained and peripheral blood lymphocytes (PBL) were cultured for cytogenetic analysis. The prooxidant/antioxidant status was determined in hemolysates by the method of hydrogen peroxide-induced chemiluminescence. RESULTS: The average level of spontaneous chromosome aberrations in PBL of the patients was (7.8 ± 0.4) per 100 metaphases, which is more than twice higher than the upper limit of the average population values. The frequency of chromosome aberrations in PBL of patients after brachytherapy session was (15.3 ± 1.0) per 100 metaphases. An increased intensity of O2- generation by PBL after brachytherapy session was also noticed. CONCLUSION: Local irradiation at a dose of 6 Gy featuring the first dose fraction of brachytherapy induces extra chromosomal aberrations in PBL of gynecological cancer patients and intensifies prooxidant processes in the blood.

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.