[The use of EPR spectroscopy to control the changes of organism radiosensitivity/radioresistance. Experimental and clinical results].

The responses of deoxyribonucleotide (dNTP), DNA and protein synthesis systems in blood-forming organs of animals (dogs, mice) as well as changes in Fe(3+)-transferrin (Fe(3+)-TF) and Cu(2+)-ceruloplasmin (Cu(2+)-CP) pools in blood to gamma-irradiation and the administration of radioprotectors have been studied. It has been shown that changes in Fe(3+)-TF and Cu(2+)-CP pools in blood are indices of changes in the body radioresistance and are reliably controlled by the EPR technique. An increase in the Fe(3+)-TF pool promotes the activated synthesis of dNTP, DNA and Fe(3+)-containing proteins which are essential for the repair efficiency during the early post-irradiation time as well as for the development of compensatory and restorative reactions of cellular systems; i.e., they are responsible for the body resistance to DNA-damaging factors. It is important that the intensity of responses depends on the initial state of the organism. It has been shown, that changes in Fe(3+)-transferrin and Cu(2+)-ceruloplasmin pools, which are trust-worthy controlled by the EPR technique in whole blood, blood plasma, and serum, as well as the changes in the extracellular DNA content in blood plasma are the markers of the changes in the organism radioresistance. This has been proved during the medical examination of the Chernobyl accident recovery workers and civil population, including children, exposed to low-intensity radiation.

[Clinical immunological disorders in children from various observation cohorts exposed to radiation factor during various stages of oncogenesis].

The immune status disorders and features depending on the radiation impact type in various cohorts of radiation observations long after the Chernobyl (CNPP) disaster and the possible role of these disorders in development of chronic somatic pathology in children are shown. Lymphocyte depletion, T-cell immunity component disorders in the form of cell contraction with CD3, CD4, CD8 markers and the B-cell immunity component disorders in the form of reducing the quantity of CD10, CD23 marker cells were observed in children subject to combined chronic irradiation by 131I, 137Cs, 90Sr radionuclides. The descendants of irradiated parents (the 1st generation; children of the Chernobyl accident consequences liquidators, children of the citizens of radiation contaminated territories with various 137Cs levels) had immunity disorders of different type. A change in the total amount of NK-cells (CD16(+)-lymphocytes) is the general sign for all radiation risk groups; however, people subject to direct radiation impact demonstrated reduction of the antitumor protection potency, whereas descendants of irradiated ones demonstrated its activation with typically increasing number of CD16(+)-lymphocytes. In all radiation risk groups, a tendency to reduction of a number of cells involved in the leukocytal activation with the "pluripotential activation" marker (CD38 marker cells), proliferating cells (CD71 marker cells) and the increase of relative amount of cells with apoptosis marker (CD95(+)-lymphocytes). Immune disorder markers under the radiation impact in various cohorts of children's observation are suggested: antigens: CD4, CD8, CD10, CD23, CD16, CD38, CB71, CD95.

[The problem of the transgeneration phenomenon of genome instability in sick children of different age groups after the accident at the Chernobyl Nuclear Power Plant].

A complex genetic examination of children which belong to two cohorts and their parents were carried out. The first cohort included children and constantly living on territories contaminated with radionuclides (Novozybkov district, Bryansk region). They were subdivided in groups according to the ontogenetic age periods of development of their parents at the time of the Chernobyl accident. In the children born in 1986-1995 the level of aberrant genomes is significantly higher as compared to the control (p < 0.001). In children born in 1998-2002 the differences are insignificant (p > 0.05). The frequency of aberrant genomes had a tendency to decrease with the period of time between the birth date of a child and the moment of the accident. Analysis of the results of cytogenetic investigation for the same living on territories with different densities of radioactive contamination (zone I-- 627-688 kBq/m2, 137Cs and zone II-- 135-402 kBq/m2, 137Cs) revealed insignificant differences in the spectrum and average frequencies of chromosome aberrations. The second cohort included children born in 1987-1991 and 1993-2002 from irradiated fathers (Chernobyl clean-up workers) and unirradiated mothers living on territories without radionuclide contamination. These children also displayed increased frequencies of aberrant genomes as compared to the control (p < 0.001). The analysis of the dynamics years of birth of cytogenetic disturbances in the same cohorts of children showed the average frequencies of aberrant genomes remain higher than the control level. In most of the children of both cohorts the repair synthesis of genome DNA by gamma- and UV-radiation is reduced as compared to one in the children from the control group.

[The organization of medical aid to children of various cohorts of supervision, undergone to the influence of small dozes of radiation].

In clause the stages of organization of medical aid to children who undergone to the influence of the ecopathologic factors, including small dozes of ionizing radiation are submitted. The features of various stages of medical aid in nearest time after influence of the radiating agent are shown. The methodological complexities of diagnostic measures in the late times after the ecopathologic influence of small dozes of ionizing radiation are submitted, the role of the radiosensitivity in formation of pathological somatic diseases of condition at children is considered. The opportunity of the differential treating and preventive help rendering to the children various cohorts of supervision is shown.

[The problem of induced genome instability as the basis of the increased morbidity in children exposed to low-intensity radiation at low doses].

The main results of the complex examination of the genome instability are presented in children constantly living on territories contaminated with radionuclides as a result of the accident at the CNPP (Novozybkov district, Bryansk region, 16-18 Ci/km2, 137Cs) and in children exposed to low-intensity radiation at different stages of ontogenetic development: children exposed to postnatal irradiation in 1986 (born before the accident), children exposed to intrauterine irradiation during the accident in 1986, children of irradiated parents born after the accident in 1987-1992 and in 1994-2000. In all examined groups of irradiated children increased frequencies of certain radiation-induced chromosome aberrations were observed as well as a reduced activity of unscheduled synthesis of genomic DNA in lymphocytes and peculiarities in individual heterozygosity of genes encoding structural and enzymatic proteins of blood. An increased radiosensitivity of lymphocyte genomes to testing in vitro irradiation and peculiarities in the dynamics of the frequencies of chromosome aberrations and sister chromatid exchanges in 3 cell generations were revealed in children from the contaminated areas. The data obtained suggest a systemic character of dysgenomic effects, the reality of induction of genome instability in the growing organism of children exposed to low-intensity radiation at low doses the expression of which is determined by individual genotypic features of the organism. Biological significance of the phenomenon of the post-radiation genome instability, its relation to the state of health and the pathogenetic role in the development of somatic pathology are postulated.

[The intellectual development of the children exposed to the influence of the ionizing radiation].

The mental development level of the children living in the territories polluted by the radioactive nuclide as the result of Cheernobil power plant damage, exposed to the prenatal irradiation, evacuated from the alienation zone, born from parents-liquidators (1st generation of the irradiated people) was evaluated. 177 children were examinated. The control group included 34 children not exposed to the radiation. The complex of psychometric methods--"D. Wexler children's intellectual test"--for 3-6-year-old children in the translation and adaptation of A.U. Panasyuk was applied for evaluating the intellect rate. In the structure of the observed groups the pathology diseases of nervous system, of digestion organs and the congenital anomalies prevailed. Clinical and instrumental investigation showed no differences in the neurology status between the observed and the control groups. It was proved that the intellect of the children exposed to the radiation corresponds the age standards. However, intellectual development of the children irradiated in the prenatal period and children evacuated from the 2nd zone of radioactive pollution (or living there) has a tendency to its decreasing. The determining role of social, of economic and of biologic factors (the parents' education, the region of living, the birth weight) in the intellect development was indicated.

[Characteristics of infection in children during prolonged oxidative stress after radiation exposure]. / Osobennosti infektsionnogo protsessa u detei v usloviiakh dlitel'nogo okislitel'nogo stressa vsledstvie radiatsionnogo vozdeistviia.

In the article on discusses the problems of origin and duration of chlamydia and herpes-virus infection in children with chronic somatic pathology and different degrees of radiation stress in contaminated territories of Brianskaya region (the level of contamination according to 137Cs = 9.37-19.73 Ci/km2).

[Evaluation of the immune and interferon status of children infected with herpes simplex virus and living in areas with increased radiation background]. / Otsenka immunnogo i interferonovogo statusov detei, infitsirovannykh virusom prostogo gerpes, prozhivaiushchikh na territorii s povyshennym radiatsionnym fonom.

Virological and immunological examinations were carried out in 52 children aged 4 to 15 living at the Bryansk district territories contaminated with radionuclides after the Chernobyl accident. The persistence of herpes simplex virus (HSV) in the blood was detected by indirect immunofluorescence in 90% of children, in 10% it was confirmed by the virus isolation in vitro in a cell culture. Specific antibodies to HSV-1 and HSV-2 were detected by enzyme immunoassay in 100% examinees, in 50% their titers surpassed those in the control group. Study of the cell-mediated immunity reactions showed increased spontaneous lymphocyte blastogenesis in 46%, a functional defect of lymphocytes upon their nonspecific stimulation with PHA mitogen and increased antigen-dependent capacity of cells to proliferation in 45%, and increased levels of circulating immune complexes in the blood and a tendency to increase of the IgG and decrease of the IgA levels in the blood serum. In addition, a quantitative imbalance was revealed in the T-cell population. Study of interferon production revealed a reduced capacity of blood lymphocytes to produce gamma-interferon and an increased production of alpha-interferon by leukocytes, as well as an increased level of circulating interferon in the serum. These data indicate a decrease of the immune status due to radiation and HSV infection.

[The host-opportunistic protozoa system. The incidence of mixed infections (Pneumocystis and cytomegalovirus) in children living in radionuclide-contaminated areas]. / Sistema "khoziain-uslovno-patogennye prosteishie". Chastota smeshannykh infektsii (pneumotsistnoi i tsitomegalovirusnoi) u detei, prozhivaiushchikh na zagriaznennykh radionuklidami territoriiakh.

The purpose of our study was to determine the influence of ionized radiation onto the frequency of mixed infections (P. carinii and Cytomegalovirus) in children inhabitants of the settlements affected with radionuclide after Chernobyl accident. Two groups of children were under survey. 1) 103 inhabitants of Novozybkov (Bryansk Province, Russia) and 38 patients under observation in Moscow paediatric hospital from another affected villages (5-15 Ci/km2) were examined serologically by the diagnostic system "Pneumo-test" and "Cytomegatest" (Nyarmedic, Moscow, Russia). Cut-off titers for P. carinii were IgM-1: 200, IgG-1: 20, for CMV IgG-1: 200, 2) Retrospective study of 563 patients with respiratory pathology and 1809 died children after acute pneumonia during 14 years period. Sputum and mucus of the patients taken by laryngoscopy and bronchoscopy were studied for P. carinii by microscopy, the section of lungs--histologically. The sediments of urine and saliva were examined for CMV by microscopy and section of different organs_-histologically. Examinations were performed by one and the same highly qualified pathologist. The results of the study were as follows. 1. Of 563 children examined for both P. carinii and CMV 186 (33%) were positive for P. carinii and 189 (33.7%) for CMV. Both pathogens were found in 46 children (8.2%), mainly among 1-2 and 6-12 month age (8.5 and 14.5%, respectively). Retrospective analysis of 1809 autopsy results shows, that in 73 cases (4%) were found only P. carinii, in 200 (11.1%) only CMV and in 24 (1.3%) two pathogens simultaneously. 2. Of 103 children surveyed serologically P. carinii monoinfection was found in 7 (8.8%), CMV-in 25 (24.3%) and coinfection in 55 (53.4%). Estimated frequency for coinfection (if combination of two infections were to be accidental) should equal 46.8%. In control group consisted of 30 children from clean Moscow region the rate of coinfection was 16.7% and estimated rate 15% (the difference between empiric and estimated rates are statistically significant, t > 4). Thus it is clear that the rate of coinfection of P. carinii and CMV is always high either in clean or in affected by ionized radiation regions. This rate determined by microscopy was higher in patients (8.2%) than in autopsy cases (1.3%) and much higher in children from affected region (53.3%) than in control (16.7%), being determined serologically. Separate interest present geometric mean titers found in the cases of coinfection. The titer for anti-CMV IgG in children from affected regions was rather high (5884 vs. 1246 in control) and on the contrary titers for anti-P. carinii IgM and IgG were lower than in control (512 vs. 1245 and 58 vs. 159 respectively). We are incline to interpret the results of our study as evidence of increased susceptibility to P. carinii and CMV in those children whose immune system was suppressed by premorbid factors or ionized radiation and peculiar symbiotic relationships of P. carinii and CMV resulting in enhancement of their infectiousness.

[The host-opportunistic protozoa system. The effect of ionizing radiation on the prevalence of cryptosporidiosis and pneumocystosis]. / Sistema "khoziain-uslovno-patogennye prosteishie". Vliianie ioniziruiushchei radiatsii na rasprostranenie kriptosporidioza i pnevmotsistoza.

The aim of this study was to determine an influence of ionized radiation on the prevalence of Cryptosporidium and Pneumocystis carinii (P. c.) infections in children inhabitants of settlements affected by radionuclides after Chernobyl accident. Survey of children from day-care centers for prevalence of Cryptosporidium was carried out in Bryansk region, Russia, and Gomel and Mogilev regions, Belarus; children from cities Mogilev and Gomel as well as small town Pochep, Bryansk region, serve as control clean zones. Survey for P. c. seroprevalence was carried out in town Novozybkov, Bryansk region, Specific Ab to P. c. determined by "Pneumo-test" system (Nyarmedic. Moscow. Russia), an evaluation of immune status included assessment of Ig in serum and saliva by Manchini method. Results of the study were as follows: 1) of 432 healthy children surveyed for Cryptosporidium oocysts 352 were from affected regions: the prevalence in Bryansk region was 8% vs. 2.8% in control, in Gomel and Mogilev 4.1% vs. 2.8%. 2) Prevalence anti-P.c. Ab accounts 56.3% in children and 78.2% in adult inhabitants of Novozybkov vs. 30% in children of control group. Special interest presents an relationship of seroprevalence P.c. and secretory immunity examined twice with 2 month interval. At the first survey IgG in seropositive for P. c. children was found in 36.8% (vs. 23.1% in control) and secretary IgA in 13.2% vs. 5.8% in control. At the second survey IgG was found in 53.4% vs. 21.8% and IgA in 2.7% vs. 1.8% in control. Taking into consideration the known fact that IgG and IgA in saliva are result of their transudation from blood through the inflammatory mucosa we consider that long ionized radiation impairs the barrier function of mucosae.

[The genetic sequelae of the Chelyabinsk and Chernobyl radioactive contaminations]. / Geneticheskie posledstviia Cheliabinskikh i Chernobyl'skikh radioaktivnykh zagriaznenii.

Genetic consequences of radioactive fall-outs of the Chelyabinsk plant producing plutonium (1949-1952) and the Chernobyl accident have been analysed. Three powerful radioactive fall-outs caused a population genetic dose of 682,801 cSv per 217,750 persons (the average dose was 2.25 cSv). Individual variations were from 1-2 mSv to 1.2 Sv or more. The population genetic dose from the Chernobyl accident was higher (32 x 10(6) man/cSv), but the individual dose was lower (mainly no more than 1 cSv). Progenic analyses of residents of radiation contaminated areas showed no increase in the incidence of congenital anomalies, spontaneous abortions, developmental microanomalies, and Down syndromes (except Byelorussia). Calculations of genetic consequences for the Ural region demonstrated that only in the most contaminated area (the average gonadal dose was 19.5 cSv); a 4.13% increase of the spontaneous level could be observed. In all other areas it was less than 1%. It is difficult to reveal possible genetic consequences of the Chernobyl accident using the real sample size of the newborns. Even in the areas with fall-outs above 15 Ci/km2, the incidence of congenital anomalies did not exceed 1% of the spontaneous level.

[Markers of the metabolic changes arising as a result of ionizing radiation exposure]. / Markery metabolicheskikh izmenenii, voznikaiushchikh vsledstvie vozdeistviia ioniziruiushchei radiatsii.

Time-related changes have been studied in the content of extracellular DNA, Fe(3+)-transferrin (TF), and Cu(2+)-ceruloplasmin (CP) in the blood plasma and the activity of ribonucleotide reductase (RR) in the tumor cells and spleen of mice during the development of acute lympholeukosis P-388 and after ionizing irradiation. At the initial stages of leucosis P-388, the content of extracellular DNA increases, the TF and CP pools in the blood plasma enlarge, and the RR activity in the tumor cells and spleen of tumoral mice markedly increases. A dose-dependent increase in RR activity was also recorded in the spleen of 5-day-old rats within 15-30 min after irradiation. The causes of these changes and the possibility for these indices to be used in estimating leucosis risk are discussed. Radiation-induced increases in RR activity are discussed in relation to the SOS-response to DNA damage; an increased pool of deoxyribonucleotides is necessary for repair of DNA. The mean contents of extracellular DNA, TF and CP in the blood plasma were obtained from children of different ages degrees of radioactive contamination suffering the consequences of the accident at the Chernobyl' Nuclear Power Station (n = 155). Groups of children have been isolated with increased, sharply decreased, and close to normal levels of extracellular DNA, TF, and CP. The lowered TF pool was observed in children with thyroid glands damaged by incorporated radioactive iodine with the degree of suppression determined by the dose. For most children subject to general irradiation, the TF and CP pools in the blood were higher than in the control, suggesting an adaptive response to irradiation.

[Dna repair activity in children exposed to small doses of ionizing radiation as a result of the accident at the Chernobyl nuclear power station]. / Reparativnaia aktivnost' DNK u detei, podverzhennykh vozdeistviiu malykh doz ioniziruiushchego izlycheniia v rezultate avarii na Chernobyl'skoi AES.

The repair activity of DNA was studied by variola vaccine virus reactivation and induced mutagenesis tests in the peripheral blood lymphocytes of children living in areas with an increased level of ionizing radiation due to breakdown at the Chernobyl' nuclear power station. A more profound repair disturbance was revealed in children living on strictly controlled territories and born after the disaster, compared to those born before it, and children living in areas where the radiation level does not exceed background values. The disturbances were characterized by increased induced mutagenesis and decreased reactivation of the variola vaccine virus. No changes in the degree of DNA repair synthesis were registered in any of the groups studied.

[The formation of an adaptive response in children exposed to the effect of low doses of radiation as a result of the accident at the Chernobyl Atomic Electric Power Station]. / Formirovanie adaptivnogo otveta u detei, podvergshikhsia vliianiiu malykh doz radiatsii v rezul'tate avarii na ChAES.

The ability of lymphocytes to form an adaptive response in cells of the children which were exposed to small radiation doses during the Chernobyl accident was studied by hydroxyapatite chromatography of cell lysates. Ten children living in the area with high radiation level (Bryansk region) and seventeen children living in the area with natural radiation level (Bryansk region too) were examined. No difference in cell ability to form adaptive response was found in both children group.