MOLECULAR GENETIC ABNORMALITIES IN THE GENOME OF PATIENTS WITH Ph-NEGATIVE MYELOPROLIFERATIVE NEOPLASIA AFFECTED BY IONIZING RADIATION AS A RESULT OF THE CHORNOBYL NUCLEAR ACCIDENT. / MOLEKULIaRNO-GENETYChNI ANOMALIÏ U GENOMI KhVORYKh NA Rh-NEGATYVNI MIIeLOPROLIFERATYVNI NEOPLAZIÏ, IaKI ZAZNALY DIÏ IONIZUIuChOÏ RADIATsIÏ VNASLIDOK AVARIÏ NA ChAES.

OBJECTIVE: to determine the frequency of major somatic mutations in the JAK2, MPL and CALR genes in the genomeof patients with Ph-negative myeloproliferative neoplasms that occur in individuals who have been exposed to ionizing radiation as a result of the Chornobyl accident. MATERIALS AND METHODS: Molecular genetic analysis of genomic DNA samples isolated from blood was performed in90 patients with Ph-negative myeloproliferative neoplasia (MPN) with a history of radiation exposure and 191patients with spontaneous MPN utilizing allele-specific polymerase chain reaction (PCR). RESULTS: The presence of major mutations in the genes JAK2, CALR and MPL was revealed in patients with MPN witha history of radiation exposure with a frequency 58.9 % (53 of 90), 12.2 % (11 of 90), and 0 % respectively, and without exposure with frequency 75.4 % (144 of 191), 3.1 % (6 out of 191) and 1.6 % (3 out of 191) respectively.Mutations JAK2 V617F in patients with spontaneous MPN were observed in each clinical form: polycythemia vera (PV),essential thrombocythemia (ET) and primary myelofibrosis (PMF). CALR mutations were detected exclusively inpatients with PMF and ET, significantly more often in groups with a radiation exposure history (18.9 % and 33.3 %,vs. 4.2 % and 6.5 %) than without one. At the same time, the occurence of MPL mutations was determined only inpatients with spontaneous MPN in 1.6 % of casees. Triple negative mutation status of genes JAK2, MPL and CALR prevailed in the group of patients with MPN with a history of radiation exposure and was 27.8 %, against 16.2 % inpatients without radiation exposure (p = 0.05). CONCLUSIONS: Genomic research of patients with Ph-negative MPN revealed features of molecular genetic damage inthose patients who were exposed to IR as a result of the Chornobyl accident and those with spontaneous MPN. Thedata obtained by determining of JAK2, MPL and CALR genes mutational status in the genome of patients with MPN isnecessary to expand the understanding of the mechanism of leukogenesis, especially caused by radiation.

CONTRIBUTION OF THE G1691A ALLELE CARRYING OF THE COAGULATION FACTOR V GENE TO THE DEVELOPMENT OF THROMBOSES IN RADIATION-EXPOSED PATIENTS WITH REACTIVE CHANGES IN PERIPHERAL BLOOD. / VNESOK NOSIISTVA ALEL'NOGO VARIANTA G1691A GENA V FAKTORU KOAGULIaTsIÏ V ROZVYTOK TROMBOTYChNYKh USKLADNEN' V OSIB Z REAKTYVNYMY ZMINAMY U PERYFERIINII KROVI, ShchO ZAZNALY RADIATsIINOGO OPROMINENNIa.

Thrombosis triggers, in addition to «classic¼ risk factors (RFs) of cardiovascular events, includes the reactive changesof peripheral blood (RCPB), markers of the hereditary thrombophilia and radiation anamnesis. However, results ofmost studies suggest the «classic¼ RFs are able to neutralize the prothrombogenic potential of the hereditary thrombophilia and other, less powerful predictors of thrombosis. OBJECTIVE: to determine the influence of the G1691A allele of the proaccelerin gene carrying to the thrombosis development, taking into account the vascular type of their occurrence, the presence of RFs in individuals with RCPB (reactive leukocytosis and thrombocytosis, and secondary erythrocytosis), as well as with and without radiation anamnesis. MATERIAL AND METHODS: In general, it was analyzed the results of clinical and molecular-genetic data of 152 patientswith RCPB, 19 patients had radiation anamnesis, 133 - did not have. The thrombotic complications were detected in5 (26.31 %) of radiation-exposer patients and 25 (18.79 %) patients without radiation anamneses. The carrying ofthe G1691A allele proaccelerin gene (APG) (Leiden mutation (LM)) was detected using the allele-specific polymerasechain reaction. RESULTS: The LM was found in 5.9 % (9 carriers) of the general cohort (GC) of RPBC patients. There were no differencein the LM frequency between the groups of patients with and without radiation anamnesis (р = 0.312). In the groupof radiation-exposer patients (р = 0.017), as well as in the group without its (р = 0.031), venous thromboses only weremore frequently in the LM carriers. In the presence of a radiation anamnesis, G1691A APG carriers with RFs have thehigher frequency (р = 0.008) and the probability of the occurrence (relative risk [RR] = 25.00; CI 95 %: 1.56-399.68)of venous thrombosis. In the group without radiation anamnesis, the frequency of venues thrombosis in the LMcarriers is higher in the younger age subgroup (р = 0.001), without RFs (p = 0.044) and without RFs under 60 years(р = 0.023). The risk of venous thrombosis in the G1691A APG carriers of the group without radiation anamnesis is5.78 (95 % CI: 1.58-21.13). In LM carriers without radiation anamnesis and RFs, as well as under the 60 years of age,the probability of venous thrombosis was 6.85 (95 % CI: 1.86-25.22) and 19.40 (95 % CI: 4.64-81.09), respectively,and in the absence of both criteria - 9.57 (95 % CI: 2.49-36.73). CONCLUSIONS: In patients with and without radiation anamnesis, the risk of venues thrombosis are observed moreoften in carriers of LM. The carrying of the G1691A APG in patients with RPBC and without RA increased the risk ofvenues thrombosis development in subjects without FRs and below 60 years of age. In the radiation-exposure group,the frequency and the risk of venues thrombosis in the G1691A APG carriers was higher in the subgroup with RFs. It isprobably due to the peculiarity of the samples, or prothrombogenic interaction between LM and radiation-associated endothelial damage.

MUTATIONS OF GENES BRCA1 AND BRCA2 IN WOMEN WITH OVARIAN CANCER EXPOSED TO FACTORS OF CHORNOBYL NUCLEAR ACCIDENT. / MUTATsIÏ U GENAKh BRCA1 TA BRCA2 U ZhINOK, KhVORYKh NA RAK IaIeChNYKIV, IaKI ZAZNALY VPLYVU ChYNNYKIV ChORNOBYL'S'KOÏ KATASTROFY.

OBJECTIVE: to determine a frequency of germline mutations 185delAG, 5382insC in BRCA1 gene and 6174delT in BRCA2 gene in Ukrainian patients with OC including women who were exposed to the factors of Chornobyl nuclear accident. MATERIAL AND METHODS: In the study we enrolled 306 OC patients of different age who were tested for the presence of the major BRCA1 and BRCA2 gene mutations using allele specific multiplex polymerase chain reaction. RESULTS: The mutation frequency in patients exposed to IR with OC (main group) was 5.3 % (2 from 38). Among unexposed patients (control group) 11,2 % (30 from 268) of cases with mutation were identified. However, the dif- ference between the groups was not significant (p = 0.39). It was shown that the BRCA1/2 mutations frequency in the patient of both groups was 10,4 % (32 from 306). The mutation BRCA1 5382insC was positive in 87.5 % (28 from 32) of cases, nevertheless nobody was identified with the allelic variant BRCA2 6174delT among both groups. There was a tendency toward an earlier age of the OC manifestation in the patients exposed to IR due to Chornobyl nuclear accident compared to BRCA-positive women of the control group (р = 0.06). When comparing BRCA-positive and BRCA-negative patients with OC of the main group, there was a statistical significance regarding the earlier age of the disease manifestation in the patients with mutations (р = 0.04). However, such difference was not observed in the control group (р = 0.22). CONCLUSIONS: The frequency of the mutations in exposed to IR and unexposed patients with OC does not differ and depends on a spectrum of studied BRCA1/2 gene mutations, level of DNA amplification and sample number. The allel- ic variant BRCA1 5382insC is dominant and accounts for 87.5 % of the total number of the found mutations. Due to the radiation factor the OC in the BRCA1-positive individuals is realized at the earlier age than in patients negative for these mutations. The incidence of OC after the Chornobyl accident was observed 27-38 years later in a cohort of women who were from 4 to 40 years old at the moment of the nuclear explosion.

Overexpression of P-glycoprotein in L1210/VCR cells is associated with changes in several endoplasmic reticulum proteins that may be partially responsible for the lack of thapsigargin sensitivity.

L1210/VCR cells, which express an abundant amount of P-glycoprotein (P-gp), were found to be resistant to thapsigargin--an inhibitor of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA). In the current paper, we have studied the possible differences among L1210 and L1210/VCR cells in expression of endoplasmic reticulum proteins involved in the regulation of calcium homeostasis and calcium-dependent processes. Amounts of mRNA encoding both calcium release channels (ryanodine receptor channels--RyR and IP3-receptor channels--IP3R) were found to be at similar levels in sensitive and resistant cells. However, mRNAs encoding IP3R1 or 2 were decreased in resistant cells cultivated in the presence of VCR (1.08 micromol/l), while mRNA encoding RyR remained unchanged. The amount of mRNA for SERCA2 was decreased in resistant cells when compared with sensitive cells. This decrease was more pronounced when resistant cells were cultivated in the presence of vincristine (VCR). Calnexin was found to be less expressed at the protein level in resistant as in sensitive cells. The level of mRNA encoding calnexin was decreased only when resistant cells were cultivated in the presence of VCR. Calnexin was found to be associated with immature P-gp in resistant cells. Thus, differences exist between sensitive and resistant cells in the expression of endoplasmic reticulum proteins involved in the control of intracellular calcium homeostasis or calcium-dependent processes. These changes may be at least partially responsible for the lack of sensitivity of resistant cells to thapsigargin.

EVALUATION OF BURDENSOME SYMPTOMS IN PATIENTS WITH RADIATION6ASSOCIATED AND SPONTANEOUS MYELOPROILIFERATIVE NEOPLASMS WITH THE USE OF OPTIMIZED SELF-ASSESSMENT MPN-SAF TSS. / OTsINKA OBTIaZhLYVYKh SYMPTOMIV U KhVORYKh NA RADIATsIINO-ASOTsIIOVANI TA SPONTANNI MIIeLOPROLIFERATYVNI NEOPLAZIÏ Z VYKORYSTANNIaM ADAPTOVANOÏ ShKALY SAMOOTsINKY MPN-SAF TSS.

OBJECTIVE: To investigate the intensity of burdensome symptoms using self-assessment MPN-SAF TSS in patientswith radiation-associated and spontaneous myeloproiliferative neoplasms (MPNs). MATERIALS AND METHODS: The study included 89 patients with radiation-associated and spontaneous MPNs, the bur-densome symptoms of MPN were determined using MPN-SAF TSS. RESULTS: The average score for complaints in patients with radiation-associated MPNs was significantly higher thanin patients with spontaneous MPNs - 43.46 and 25.04 points, respectively (p = 0.003). MPN patients classified bysubtypes also showed differences regarding intensity of burdensome MPN symptoms, demonstrating significantlyhigher average score of complaints among primary myelofibrosis patients (35.60), compared to polycythemia vera(29.60) and essential thrombocythemia (18.05) patients, (p = 0.005). Our study did not reveal any influence of theJAK2 V617F mutation on MPN burdensome symptoms intensity in MPN patients. CONCLUSIONS: We demonstrated a higher intensity of the MPN burdensome symptoms determined by the optimizedself-assessment MPN-SAF TSS in patients with radiation-associated, and in primary myelofibrosis patients, indicat-ing increased severity of patient's general conditions at the stage of diagnosis verification. It is advisable to usethe optimized MPN-SAF TSS at the moment of molecular genetic testing during the diagnosis of MPN for selectionor modifying treatment strategies in order to achieve better quality of life for patients.

Radioprotective properties of sodium humate in radiation-induced mutagenesis in cultured lymphocytes of thyroid cancer patients.

UNLABELLED: To investigate the effect of sodium humate on the level of cytogenetic damage in culture of lymphocytes of patients with thyroid cancer after γ-irradiation. MATERIALS AND METHODS: Metaphase analysis of chromosome aberrations in cultured peripheral blood lymphocytes of 10 individuals with thyroid cancer was performed after irradiation of lymphocytes in vitro at a dose of 1 Gy from (137)Cs source at the early G0 phase of cell cycle. Sodium humate was added to cell culture for 30 ± 15 min after phytohemagglutinin stimulation at concentrations of 10 and 100 µg/ml. RESULTS: Sodium humate exhibited antimutagenic properties. The preparation at a concentration of 10 µg/ml was more effective than at a concentration of 100 µg/ml, reducing the average incidence of radiation-induced chromosome aberrations by 51.88 and 38.77%, respectively. The most pronounced antimutagenic effect of sodium humate was the reduction of the frequency of chromosomal type aberrations, however, such efficiency varied between individual patients with thyroid cancer. CONCLUSIONS: Sodium humate could be considered as a potential therapeutic modifier of radiation damage.

Modification of radiation induced chromosome damage in Allium test by sodium humate. / MODYFIKATsIIa GUMATOM NATRIIu RADIATsIY̆NO INDUKOVANYKh POShKODZhEN' KhROMOSOM V ALLIUM TESTI.

OBJECTIVE: Cytogenetic analysis of the effects of sodium humate in induced γ irradiation mutagenesis in Allium test. MATERIALS AND METHODS: Analysis of the root meristem cells of Allium cepa L. seeds carried by ana telophase. Inves tigated the effect of sodium humate (100 mg/l) on cytogenetic effects γ irradiation (137Cs) at doses of 5, 10 and 20 Gy. RESULTS: Antimutagenic effect of sodium humate was revealed, what allows to consider it as potential therapeutic modifier of radiation damage. Antimutagenic effect of sodium humate increased with increasing irradiation dose. Spotted differential activity of the drug with respect to various types of aberrations are most effectively reducing the frequency of radiation markers mutagenesis - chromosomal aberrations manifested in lower efficiency of long term survivors against potential changes of chromosomes compared with short lived. CONCLUSIONS: Revealed different mechanisms for implementing antimutagenic properties of sodium humate in con dition of γ irradiation induced mutagenesis in Allium test.

Polymorphism of DNA repair gene XPD Lys751Gln and chromosome aberrations in lymphocytes of thyroid cancer patients exposed to ionizing radiation due to the Chornobyl accident.

The aim of this work was to analyze the relationship between polymorphisms of DNA repair gene XPD Lys751Gln and frequency and spectrum of chromosome aberrations in the culture of peripheral blood lymphocytes of thyroid cancer (TC) patients having been exposed to ionizing radiation due to the Chornobyl accident. MATERIALS AND METHODS: XPD Lys751Gln polymorphisms were detected by polymerase chain reaction in 102 TC patients including 38 patients exposed to ionizing radiation due to Chornobyl disaster (Chornobyl recovery workers, evacuees, and the residents of contaminated areas), 64 patients without history of ionizing radiation exposure and 45 healthy residents of Ukraine as control group. RESULTS: In homozygous carriers of the minor allele XPD Gln751Gln, exposed to ionizing radiation, the significantly increased risk of TC (odds ratio = 3.66; p = 0.03; 95% confidence interval 1.04-12.84) was found. Among evacuees and residents of contaminated areas, homozygous carriers of the minor allele variants of XPD gene were characterized by the high level of spontaneous chromosome aberrations. TC patients without history of ionizing radiation exposure, being homozygous carriers of the allele XPD Lys751Lys, had significantly reduced frequency of chromosome-type aberrations. CONCLUSIONS: The carriage of homozygous minor allele of DNA repair gene XPD Gln751Gln is a risk factor for TC in persons from Ukrainian population exposed to ionizing radiation and is associated with the increased levels of chromosomal instability. This article is a part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

The contribution of hereditary thrombophilia to increasing the frequency of thrombosis in patients with Ph negative myeloproliferative neoplasms, including the victims from the Chornobyl accident. / VNESOK SPADKOVOÏ TROMBOFILIÏ V ZBIL'ShENNIa ChASTOTY TROMBOZIV U KhVORYKh NA Ph NEGATYVNI MIIeLOPROLIFERATYVNI NOVOUTVORENNIa, VKLIuChAIuChY POSTRAZhDALYKh VNASLIDOK AVARIÏ NA ChORNOBYL'S'KIY̆ ATOMNIY̆ ELEKTROSTANTsIÏ.

OBJECTIVE: The definition of a contribution of the carriage of the G1691A allele of thecoagulation factor V gene and the G20210A allele of the coagulation factor II gene in the development of thrombosis in Ph negative myeloprolifer ative neoplasms (MPN) patients, who were irradiated in the dose range 0,001 0,99 Gy and who were not. MATERIALS AND METHODS: The clinical and molecular genetic characteristics of patients with radiation associated and spontaneous polycythemia vera (PV), essential trombotsytemiya (ET) and primary myelofibrosis (PMF) were ana lyzed. The group of radiation associated PV, ET and PMF represented by 35, 10 and 22 patients respectively, and the cohort of spontaneous PV, ET and PMF - 149, 111 and 78 patients respectively. RESULTS AND CONCLUSIONS: The carriage of any of the two molecular genetic markers of hereditary thrombophilia at spontaneous PMF increases the frequency (3 of 6 vs 8 of 72; p = 0.033) and risk (RR = 6.09; 95 % CI = 1.40-26.43) of thrombosis. The presence of the G1691A allele of the proaccelerin gene in patients with PMF, who were not exposed to ionizing radiation, causes increase the likelihood of venous thrombosis at 10.14 times (95 % CI = 1.67-61.33). At spontaneous and radiation associated Ph negative MPN (in individuals exposed to doses in the range 0,001-0,99 Gy), the higher rate of the occurrence of venous, arterial and any thrombosis was observed in carriers of the G1691A allele the coagulation factor V gene, than in those, whose have the wild type allele. In particular, the G1691A allele of the proaccelerin gene carriers, that are belonged to the group of patients with radiation associated PV, have at 33.33 person years bigger rate of any thrombosis (95 % CI = 0.22-100.00, p = 0.048) and venous vascular events (95 % CI = 12.50-50.00; p = 0.003).In PMF patients with a radiation anamnesis were found the difference (20.00 person years; 95 % CI = 1.51-50.00, p = 0.035) between the ratio of any thrombosis and arterial vascular events, which was calculated for the G1691A allele of the proaccelerin gene and for those, who have the wild type allele. The carriers of the G20210A nucleotide variant of the coagulation factor II gene with spontaneous ET and PMF, compared with patients with the wild type allele, have a higher rate of venous thrombosis per 100 patient years.

[Determination of BCR/ABL translocation in radiation-associated acute myeloid leukemia patients by fluorescence in situ hybridization].

We report the results of BCR/ABL translocation analysis on interphase leukemic cells of 33 acute myeloid leukemia (AML) patients by fluorescence in situ hybridization. Of these, there were 13 persons exposed to ionizing radiation due to the Chernobyl accident with radiation-associated AML and 20 patients with spontaneous disease. BCR/ABL translocation which was detected in 4 and I case respectively may play an important role in radiation-induced leukemigenesis.

[P-glycoprotein expression in radiation-associated acute myeloid leukemia].

The article presents findings of the analysis on P-glycoprotein expression of leukemic cells in 52 acute myeloid leukemia (AML) patients. Of these, there were 20 persons exposed to ionizing radiation due to the Chernobyl accident and 32 patients with spontaneous disease. Leukemic cells in patients with radiation-associated AML compared to spontaneous cases more often were P-glycoprotein positive (12/20 vs 9/32, P<0,05). P-glycoprotein overexpression significantly correlated with resistant disease in patients with radiation-associated AML, but was not a prognostic variable for treatment outcome in terms of overall survival.

Predictive value of laboratory hematological parameters for thromboses development in patients with spontaneous and radiation associated Ph negative myeloproliferative neoplasms. / PROGNOSTYChNA TsINNIST' GEMATOLOGIChNYKh POKAZNYKIV ShchODO VYNYKNENNIa TROMBOZIV U KhVORYKh NA SPONTANNI TA RADIATsIYNO ASOTsIYOVANI Rh NEGATYVNI MIIeLOPROLIFERATYVNI NOVOUTVORENNIa.

OBJECTIVE: To establish which of hematological parameters have discriminatory ability for forecast the development of thromboses in spontaneous and radiation associated Ph negative myeloproliferative neoplasms (MPN). MATERIALS AND METHODS: It was analyzed hematological parameters of 85 patients with polycythemia vera (PV), 43 - essential thrombocythemia (ET) and 40 - primary myelofibrosis (PMF). The main group consisted of patients (PV = 18, ET = 6, PMF = 18) which were exposed to ionizing radiation due to the Chornobyl accident, and control - patients (PV = 67, ET = 37, PMF = 22) without affecting emergency radiation in history. RESULTS: It was determined, that in spontaneous PV predictive for the thromboses development value of the hema tocrit and the leukocytes is > 55 % and > 13.2 · 109/l respectively, and the total cholesterol is > 5.7 mmol/l. The effi ciency such factor as the "hematocrit > 55 %" (area under the curve - AUC = 0.67; p = 0.023) and the "leukocytes > 13.2 · 109/l "(AUC = 0.66; p = 0.011) is average for the predicting of thromboses, and the "total cholesterol > 5.7 mmol / l" (AUC = 0.92; p < 0.0001) is excellent. In radiation associated PV and spontaneous ET predictor of thromboses was the platelet count < 440.0 · 109/l and the leukocytes > 10.0 · 109/l respectively, and it character ized by very good (AUC = 0.84; p = 0.0002 and AUC = 0.72, p = 0.019, respectively) predictive power. In the main and in the control group of PV patients was determined the same AUC for application the "hematocrit> 55 %" (p = 0.800) and the "leukocytes > 13.2 · 109/l" (p = 0.831) in the thromboses prediction, but it was calculated dif ferent AUC for the "platelets < 440.0 · 109/l" (p = 0.0004). Therefore, the use such PB index as the "platelets < 440.0 · 109/l" for the thromboses risk assessment is appropriate only in PV patients with a history of radiation, the "hematocrit < 55 %", the "leukocytes < 13.2 · 109/l" - in the patients who suffered from the Chornobyl accident and in the persons affected by IR exclusively within the natural background radiation. In the main and in the control group of patients with ET is no difference between the AUC of the factor "leukocytes > 10.0 · 109 / l" (p = 0.509), so it can be used at spontaneous and radiation related ET.

Specifics of the course and the clinical pictures of essential thrombocythemia depending on the JAK2V617F status of the patients. / OSOBLYVOSTI PEREBIGU TA KLINIChNOI KARTYNY ESENTsIAL'NOI TROMBOTsYTEMII ZALEZhNO VID JAK2V617F STATUSU KhVORYKh.

OBJECTIVE: The purpose of the study was to analyze the specific features of the relationship between the JAK2 V617Fmutation and clinical presentation, and risks of thrombosis in patients with spontaneous and radiation associated essential trombocitemia (ET). MATERIALS AND METHODS: Clinical, laboratory hematological, molecular genetic characteristics of ET patients were analyzed. The group of patients with radiation associated ET was represented by 10 individuals and the cohort of spontaneous ET represented by 111 persons. RESULTS: The JAK2V617F positive mutation status in patients with spontaneous ET is the predictor of the increase of distribution of thrombosis (23.0 % vs. 6.0 %), risk of its development (relative risk = 1.5; 95 % confidence interval = 1.3-1.8), and the decrease of survival without thrombosis. It has been proved that presence of the JAK2V617F mutation increases the probability of venous thrombosis (relative risk = 1.5; 95 % confidence interval = 1.30-1.7) in spontaneous ET patients. The use of the JAK2V617F mutation status of patients with spontaneous and radiation associated ET (AUC = 0.62 and AUC = 0.68 respectively) complies with the average power marker for the prediction of thrombosis. The carriage of the JAK2V617F mutation in patients with spontaneous and radiation associated ET is characterized by a higher (93.9 % and 100 % accordingly) indicator of predictive value of a negative result to deter mine of the risk of thrombosis. ET patients with the JAK2V617F mutation were found to have a higher average value of erythrocytes, hemoglobin, mean corpuscular volume and lower erythrocyte sedimentation rate in their peripher al blood, when compared to those without the mutation. Trepanobioptat samples of JAK2V617F positive ET patients exhibited a prevalence of moderate hypercellularity of bone marrow, large and giant forms of megakaryocytes, reti culin fibrosis and microcirculation disorders compared to individuals without the mutation. A greater number of average quantities of leukocytes in JAK2V617F positive patients with radiation associated ET were found compared to JAK2V617F negative persons.

Research of DNA repair genes polymorphism XRCC1 and XPD and the risks of thyroid cancer development in persons exposed to ionizing radiation after the Chornobyl disaster. / DOSLIDZhENNIa POLIMORFIZMU GENIV REPARATsIi DNK XRCC1 TA XPD TA RYZYKU VYNYKNENNIa RAKU ShchYTOPODIBNOi ZALOZY U OSIB, IaKI ZAZNALY DIi IONIZUIuChOi RADIATsIi VNASLIDOK AVARIi NA ChORNOBYL'S'KIi AES.

OBJECTIVE: The objective of this work was to determine and compare the features of DNA repair gene XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in patients with thyroid cancer (TC), who were exposed to ionizing radiation (IR) as a result of the Chornobyl disaster, and in patients without exposure to ionizing radiation in history. MATERIALS AND METHODS: Determination of gene XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms was performed by polymerase chain reaction (PCR) in 102 patients with thyroid cancer: 38 people, who were exposed to ionizing radiation due to Chornobyl disaster (members of the accident, and evacuees and residents from controlled areas contaminated with radionuclides), 64 individuals without exposure to ionizing radiation in history and 41 persons residents of Ukraine without cancer pathology in the control group. For comparison of the data on spontaneous and radiation-associated thyroid cancer and settlement of allele frequencies differences and risk of cancer pathology were used the literature data on control groups of populations of Russia, Belarus and Poland. RESULTS: Comparing to the literature data on XRCC1 Arg399Gln polymorphisms in radiation-exposed individuals without cancer pathology, the risk of thyroid cancer in homozygous minor allele XRCC1 Gln399Gln carriers, who were exposed to ionizing radiation was significantly increased: OR = 4,14, p = 0,001 (CI95 % 1,72-9,93). In homozygous carriers of the minor allele of the gene XPD Lys751Gln, exposed to IR, revealed increased risk of thyroid cancer: OR = 3,30, p = 0,05 (CI 95 % 0,82-14,14), when compared with the control group of Ukrainian population. CONCLUSIONS: The carriage of homozygous minor allele Gln399Gln XRCC1 and XPD Gln751Gln of DNA repair genes is a risk factor for thyroid cancer under the influence of ionizing radiation in research group of Ukrainian population.

[Long-term results of treatment of chronic B-cell lymphoid leukocytes in persons who participated in the elimination of the effects of the nuclear accident at the Chernobyl nuclear station]. / Rezul'taty likuvannia khronichnoho B-klitynnoho limfoleikozu v uchasnykiv likvidatsiï naslidkiv avariï na ChAES u viddalenomu periodi.

Clinical-and-hematological characteristics are presented of B-cell chronic lymphoid leukosis in those persons who took part in the elimination of the effects of the Chornobyl accident in the remote period. Results are highlighted of treatment of 16 patients with making use of different chemical drug preparations. Employment of fludarabin and cyclophosphan combined in treatment of the medical condition in question has been shown to promote long-term complete and partial remissions in a major proportion of patients, which effect was not achievable with standard means of remediation. A side effect of fludarabin was leukocytopenia that in the presence of changed immunity threatened the patients with development and exacerbation of infections complications. Use of manax and erbisol moderated the immunosuppressive and toxic action of fludarabin, due to which fact infectious complications and drug-induced hepatitis have came to be less common, the patients' quality of life gotten better.

Cytogenetic analysis of radioprotective properties of sodium lignogumate after gamma-exposure in Allium-test. / Citogeneticheskij analiz radioprotektornyx svojstv lignogumata natriya pri gamma-obluchenii v ALLIUM-teste.

Objective. Comprehensive cytogenetic analysis of the effects of sodium lignohumate in induced γ-irradiation mutagenesis in Allium-test. Materials and methods. Analysis of the root meristem cells of Allium cepa L. seeds carried by ana-telophase. Lignohumate investigated the effect of sodium (100 mg/l) on cytogenetic effects γ-irradiation (137Cs) at doses of 5, 10 and 20 Gy. Results. Polyfunctionality lignohumate sodium antimutagen as provided by the presence not only antioxidant properties, but other antimutagenic mechanisms. Thus Lignohumate sodium exhibits radioprotective properties of the therapeutic. Stimulation of repair processes influenced lignohumate depends on the radiation dose. It is most effective at a dose of 5 Gy. Upon irradiation at doses of 10 Gy and 20 predominate, other mechanisms, including stimulation of apoptosis and repopulation. Spotted differential activity of the drug with respect to various types of aberrations are most effectively reducing the frequency of radiation markers mutagenesis - chromosomal aberrations manifested in lower efficiency of long term survivors against potential changes of chromosomes compared with short-lived. Conclusions. Revealed multiple mechanisms for implementing antimutagenic properties lignohumate sodium γ-irradiation-induced mutagenesis in Allium-test.

Allelic polymorphism of DNA repair gene XRCC1 in patients with thyroid cancer who were exposed to ionizing radiation as a result of the Chornobyl accident. / Alel''nyj polimorfizm gena reparacii' DNK XRSS1 u hvoryh na rak shhytopodibnoi' zalozy, jaki zaznaly dii' ionizujuchoi' radiacii' vnaslidok avarii' na Chornobyl''s''kij AES.

Objective - to determine and compare the features of DNA repair gene XRCC1 Arg399Gln polymorphisms in patients with thyroid cancer (TC), who were exposed to ionizing radiation as a result of the Chornobyl disaster, and in patients without exposure to ionizing radiation in history. Materials and methods. Determination of gene XRCC1 Arg399Gln polymorphisms was performed by polymerase chain reaction (PCR) in 102 patients with thyroid cancer: 38 people, who were exposed to ionizing radiation due to Chornobyl disaster (clean-up workers, evacuees and residents from controlled areas contaminated with radionuclides) and 64 individuals without exposure to ionizing radiation in anamnesis. The literature data on control groups of populations of Russia and Belarus were used for comparison of the data on spontaneous and radiation-associated thyroid cancer and calculation of allele frequencies differences and risk of cancer pathology. Results. Frequency of minor allele Arg399Gln XRCC1 gene and homozygous carriers of this allele in patients with thyroid cancer, who were exposed to ionizing radiation due to Chornobyl disaster was significantly higher than in patients without exposure to ionizing radiation in anamnesis (0.57 and 0.37, p = 0.006 and 34.21 % and 7.81 %, p = 0.001, respectively). Comparing to the literature data on XRCC1 Arg399Gln polymorphisms in radiation-exposed individuals without cancer pathology, the risk of thyroid cancer in homozygous minor allele XRCC1 Gln399Gln carriers, who were exposed to ionizing radiation was significantly increased: OR = 4.14, p = 0.001 (CI95 % 1.72-9.93). Conclusions. The carrying of homozygous minor allele Gln399Gln of DNA repair gene XRCC1 is a risk factor for thyroid cancer under the influence of ionizing radiation in research group of Ukrainian population.

MYC gene rearrangements detected by interphase fluorescence in situ hybridization in diffuse large B-cell lymphomas. / MYC perebudovy dyfuznyh krupnoklitynnyh B-limfom, vyjavleni za dopomogoju interfaznoi' fluorescentnoi' IN SITU gibrydyzacii'

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, including approximately 30-40% of all B-cell non-Hodgkin lymphomas (B-NHL). Chromosomal translocations are the hallmark of genetic aberrations in B-lymphoma and are often associated with a specific subtype of B-NHL. MYC gene dysregulation due to chromosomal translocations is characteristic for the most cases of Burkitt's lymphoma. Objective. The goal of this study was to improve the diagnostic accuracy of DLBCL. Identification of chromosome 8 and 14 abnormalities including the translocation of MYC gene t(8; 14)(q24; q32) in substrate cells of lymph nodes was applied using the method of tri-color interphase fluorescence in situ hybridization (I-FISH). Materials and methods. Lymph node biopsy specimens of 17 patients with diffuse large B-cell lymphoma and three patients with Burkitt's lymphoma (including one participant of liquidation of consequences of the catastrophe at the Chornobyl NPP) were studied. The age of patients ranged from 10 to 66 years old (41.3 ± 3.7 average). Biopsy specimens fixed in paraffin. I-FISH-analysis was performed using the commercial test Vysis IGH/MYC, CEP 8 tri-color, dual fusion translocation probe (Abbott Molecular, USA). Results and conclusions. MYC gene and immunoglobulin heavy chain (IGH) gene translocations were found in four out of twenty persons. Consequently the I-FISH method allows identification of of MYC and IGH gene rearrangements in tissue cells substrate of lymphoma fixed in paraffin. Using this method the molecular-cytogenetic abnormalities were found in eight of twenty patients with B-cell lymphoma providing verification of the lymphoma diagnosis, prediction of their clinical course and advance in management i.e increase the effectiveness of therapy, in refractory lymphoma cases among others.

Clinical risk factors of thrombosis in patients with Ph-negative myeloproliferative neoplasms, who had experienced radiation exposure due to the Chornobyl accident.

OBJECTIVE: The objective of this study was to determine the predictive value of a factor of age over 60 years, history of thrombosis, and cardiac risk factors (CRF) for the thrombosis in patients with Ph-negative myeloproliferative neoplasm (Ph-negative MPN), namely the essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (IMF), who had experienced radiation exposure due to the Chornobyl accident and without radiation anamnesis. MATERIALS AND METHODS: There were 216 patients with Ph-negative MPN included in the study. Prevalence of thrombosis and presence of CRF were determined by processing the medical documentation. RESULTS: The age older than 60 years (RR=1.73, 95% confidence interval [CI] 1.00-2.98; p=0.043 and RR=2.04, 95% CI =1.12-3.68; p=0.02) and CRF (RR=2.25, 95% CІ =1.21-4.16; p=0.005 and RR=2.31, 95% CІ =1.20-4.41; p=0.008) are predictors of thrombosis in all patients with PV and with spontaneous PV, respectively. Age over 60 years and CRF in all patients with ET associates with an increase of the relative risk of thrombosis (RR=2.5, 95% CІ =1.05-5.92; p=0.047 and RR=2.74, 95% CІ =1.18-6.23; p=0.026). Frequency of recurrent thrombotic complications in patients with ET and thrombosis in anamnesis is significantly higher than in patient's without history of thrombotic complication (RR=2.75, 95% CІ =1.15-6.51; p=0.035). CONCLUSIONS: Our findings confirm previous results of other studies reporting that the age over 60 years, history of thrombosis, CRF influences on thrombosis development in Ph-negative MPN patients.

Prognosis of probability of BRCA1 and BRCA2 mutations carriage in women with compromised family history of breast and/or ovarian cancer.

UNLABELLED: Burdened family history of breast and/or ovarian cancer may indicate the mutations carriage in the BRCA1 and BRCA2 genes. OBJECTIVE: Estimation and compare of the Manchester Scoring system, Penn II and Myriad algorithm in an ability to distinguish the cases with BRCA1/2 mutation those and no mutant alleles at the individual level among the Ukrainian women with early onset of a breast cancer and/or compromised family history with breast cancer and/or ovarian cancer. MATERIAL AND METHODS: Results of genealogy, molecular genetic and morphological study from 44 females with breast cancer, with early development of the disease or family history of a breast cancer and/or ovarian cancer were the material of research. Determination of carriers BRCA1 and BRCA2 mutations among women was performed by Manchester Scoring system and Penn II and Myriad algorithm. RESULTS AND CONCLUSIONS: Manchester Scoring system has better capacity to distinguish patients with and without mutant alleles at the individual level. The area under the curve of Manchester Scoring system is 0.84, Penn II - 0.66, Myriad - 0.68.