The Intensity of Blood Lymphocyte Apoptosis in Chronically Exposed Individuals with Obligate Forms of Precancerous Conditions.

We studied the apoptotic death of peripheral blood lymphocytes in individuals chronically exposed to radiation with a history of obligate forms of precancerous conditions. The study included 242 subjects chronically exposed to low-intensity radiation in the range of low and medium doses (mean dose of irradiation of the red bone marrow 555±39 mGy). Of these, 121 subjects had obligate forms of precancerous conditions. In irradiated individuals with obligate forms of precancers, a statistically significant increase in the frequency of apoptosis of peripheral blood lymphocytes at an early and late stages was revealed. Correlation analysis revealed no dependence of the apoptotic death of peripheral blood lymphocytes on the dose of red bone marrow irradiation.

[Influence of synthetic peptide of active GM-CSF center on hemopoiesis recovery in C57Bl/6 mice after exposure to fractionated radiation].

The research allowed evaluation of the influence exerted by synthetic peptide of the active center of granulocyte-macrophage colony-stimulating (GM-CSF) factor on hematopoiesis in mice both under normal physiological conditions of the animals, and during the period of post-exposure recovery of hematopoiesis. It has been demonstrated that a synthetic peptide of the active GM-CSF center is able to exert a stimulating effect on animals with radiation-induced hematopoiesis inhibition. A single injection of the preparation at a dose of 0.005 µg/g to female C57Bl/6 mice, which had been exposed to fractionated exposure at a dose of 10 Gy and developed inhibition of bone-marrow hematopoiesis and cytopenia, exerted a stimulating effect on the granulocyte and monocyte lineages of hemopoiesis. Injections of an active GM-CSF center peptide to irradiated animals did not influence the content of CFUs in thebone-marrow (BM), but they exerted a stimulating influence on the population of these cells in unexposed animals. No effect of the influence of the preparation on the development of extramedullary hematopoiesis in the spleen was observed in the irradiated mice. The study showed that a peptide active site GM-CSF is a promising drug in terms of its use for the treatment of radiation-induced myelosuppression.

[Changes in cellular radiosensitivity after low dose irradiation].

When the adaptive response (AR) was studied on human blood lymphocytes, a new dependence was discovered. This dependence defines the direction of the radiosensitivity change after a low dose of irradiation. Using micronucleus (MN) test with cytochalasin B the dependence between the cell reaction after low level irradiation and radiosensititvity (the effect after irradiation at the dose of 1 Gy) was observed. The negative correlation between the frequency of AR manifestation, sensibilization, intermediate links and radiosensitivity was discovered. This regularity is observed in the population of Moscow, Obninsk, Chelyabinsk region (irradiated and control) inhabitants, Chernobyl accident liquidators, Moscow children, in individuals with Hodgkin's lymphoma before and during treatment. The negative correlation is also noted by AR determination with two irradiation schemes: in one or two different cell cycle phases (G1-G1 or G1-G2). Similar links are observed using the chromosome methaphase analysis (the frequency of cells with chromosome aberrations). So, the results of the experiments conducted allow us to suppose that the connection between the cell radiosensitivity and a different type of reaction after low dose irradiation--from AR to the increase in radiosensitivity (sensibilization) is a general regularity. AR is induced by low level irradiation and high cell radiosensitivity, while sensibilization is induced by low radiosensitivity. Since AR and sensibilization can be induced not only by irradiation, but many different chemicals and physical agents, the described correlation can be observed in the case of different exposures. Cellular AR and sensibilization are integral indexes depending on many genetic and epigenetic factors, as well as on the initiation of a large number of events. However, the discovered mechanisms of interrelations are still difficult to explain.

[Phytoplankton and zooplankton of the industrial reservoir R-9 (Lake Karachay)].

Planktonic communities of the Reservoir-9 (Lake Karachay, storage reservoir of liquid medium-level radioactive waste of the Mayak Production Association) are exposed to the severe radioactive forcing (in 2010 the total beta-activity of the water was 1.8 x 10(7) Bq/L, total alpha-activity was 1.1 x 10(4) Bq/L), aswell as to the chemical contamination (level of nitrates in water 4.1 g/L). The calculated values of the absorbed dose rate were 130 Gy/day for phytoplankton and 4.0 Gy/day for zooplankton. Extremely low species diversity, the overwhelming dominance of one species (phytoplankton is close to a monoculture of ubiquitous cyanobacteria Geitlerinema amphibium, zooplankton--to a monoculture of rotifers Hexarthrafennica), wide fluctuations in numbers of algae, a low number of zooplankton were the most substantial characteristics of the plankton communities in Lake Karachay. So, plankton communities status is a sign of environmental retrogress in this ecosystem.

[Status of hemapoiesis in residents of the Techa riverside villages in the period of maximum radiation exposure. Report 1. Evaluation of the cellular composition of peripheral blood and the role of comorbidities in the oppression of hemapoiesis].

Residents of the Techa riverside villages chronically exposed to ionizing radiation (the average dose rate in 1951-1956 was 0.047 Gy/year, the maximum reached 2.44 Gy/year) developed marked changes in the cellular composition of peripheral blood. The maximum reduction of peripheral blood counts occurred in the years 1951-1953, after which the beginning of the restoration of cellularity to the control level was observed. The dose rate at this point (1956) was about 0.02 Gy/year. The factors of radiation and non-radiation nature (gender, the age at the onset of exposure, health related disorders) in different combinations affect the number of peripheral blood cells. The influence of dose rate of a chronic radiation exposure on a platelet count takes precedence over other factors. The factors of gender and dose rate determine the number of erythrocytes in exposed persons. The changes accompanying the health status and dose rate significantly affect the number of neutrophils. The influence of comorbidity, age and dose rate on the number of monocytes was noted. A lymphocyte count was mainly determined by the age at the onset of exposure and concomitant diseases. A joint influence of chronic radiation exposure and concomitant diseases increases a mutual action on erythro- and thrombocytopoiesis. The decrease of the dose rate was followed by a gradual predominance of the somatic disease influence on leukocyte (neutrophils, lymphocytes and monocytes) counts.

[Status of hemapoiesis in residents of the Techa riverside villages in the period of maximum radiation exposure. Report 2. Influence of exposure dose and dose rate of red bone marrow as well as modifying factors on the frequency of cytopenia and cytosis].

The purpose of this study is a retrospective estimation of the influence of dose and dose rate of the red bone marrow chronic radiation exposure in combination with various modifying factors (gender, age, comorbidity) on the frequency of deviations from normal values of the results of peripheral blood investigation in humans exposed on the Techa River. The results of investigation show that humans chronically exposed to radiation can develop marked changes in the cellular composition of peripheral blood characterized by a tendency to cytopenia (signs of the decompensation of hemopoiesis). The tendency to cytopenia can be identified earlier in the lymphoid germ, and later in platelet and erythroid lines. A high lability of granulocytes under the influence of various, often infectious, factors is the cause of the lack of statistically significant differences in terms of frequency of neutropenia. Several non-radiation factors (gender, age, health status) in combination with radiation exposure could have a modifying influence on hematopoiesis, which contributed to the disruption of adaptation processes and the development of conditions characterized by a tendency to cytopenias in exposed individuals. The red bone marrow dose rate reduction resulted in a gradual decrease in the frequency of erythrocytopenia, thrombocytopenia, neutropenia and lymphocytopenia in the group of exposed population. Increased frequencies of erythrocytosis, thrombocytosis, lymphocytosis, monocytosis and neutrophilia were observed when the median dose rate was reduced to the level of 0.024 Gy/year (in the year 1956), which could be regarded as activation of regenerative processes in hematopoiesis.

[Assessment of radiation exposure level for hydrobionts in some special industrial ponds at the "Mayak" PA].

Evaluation of the radionuclide content in the ecosystem components (water, sediments, aquatic organisms) of industrial reservoirs-storages of liquid radioactive waste of the "Mayak" PA (reservoirs R-4, R-10, R-11, R-17, R-9) and the estimation of the absorbed dose rate in aquatic organisms of these reservoirs using the software package ERICA Assessment Tool 1.0 May 2009 have been performed. Gradient of the absorbed dose rate for the detected taxonomic groups of hydrobionts in the series of the studied reservoirs R-11 --> R-10 --> R-4 --> R-17 --> R-9 was almost equal to one order of magnitude. The estimated absorbed dose rate for phytoplankton ranged from 5.4 x 10(0) mGy/day (R-11) to 4.0 x 10(4) mGy/day (R-9), for zooplankton--from 6.4 x 10(-1) mGy/day (R-11) to 3.8 x 10(3) mGy/day (R-9), for zoobenthos (chironomids)--from 5.6 x 10(0) mGy/day (R-11) to 1.1 x 10(3) mGy/day (R-17), for fish (roach)--from 8.0 x 10(-1) mGy/day (R-11) to 1.9 x 10(1) mGy/day (R-4).

[Assessment of erythrocytes pathology level in peripheral blood in roach (Rutilus rutilus L.) from reservoirs with different levels of radioactive contamination].

In summer 2009, the level of pathology of erythrocytes was assessed in the peripheral blood of roach (Rutilus rutilus L.) from the reservoirs for water-storage of low level radioactive waste of PA "Mayak". Roach from the Shershny reservoir and the Buffer reservoir (Chelyabinsk region) was used as a control. Radionuclide maintenance in water, sediment, and roach was determined and dose rates for the roach were calculated using the software package ERICA Assessment Tool 1.0 May 2009. It is revealed that chronic radiation exposure with the dose rates in the range from 0.8 up to 19 mGy/d leads to a twofold increase in the frequency of erythrocytes with micronuclei in peripheral blood, dose-dependent increase in the frequency of red blood cells with the nuclear pyknosis and causes no significant increase in the level oferythrocyte amitosis. It is suggested that the frequency rate of apoptosis in peripheral blood erythrocytes of the fish could be used in the biological monitoring of contaminated aquatic ecosystems.

[Distribution of individuals by spontaneous frequencies of lymphocytes with micronuclei. Particularity and consequences].

By micronucleus (MN) assay with cytokinetic cytochalasin B block, the mean frequency of blood lymphocytes with MN has been determined in 76 Moscow inhabitants, 35 people from Obninsk and 122 from Chelyabinsk region. In contrast to the distribution of individuals on spontaneous frequency of cells with aberrations, which was shown to be binomial (Kusnetzov et al., 1980), the distribution of individuals on the spontaneous frequency of cells with MN in all three massif can be acknowledged as log-normal (chi2 test). Distribution of individuals in the joined massifs (Moscow and Obninsk inhabitants) and in the unique massif of all inspected with great reliability must be acknowledged as log-normal (0.70 and 0.86 correspondingly), but it cannot be regarded as Poisson, binomial or normal. Taking into account that log-normal distribution of children by spontaneous frequency of lymphocytes with MN has been observed by the inspection of 473 children from different kindergartens in Moscow we can make the conclusion that log-normal is regularity inherent in this type of damage of lymphocytes genome. On the contrary the distribution of individuals on induced by irradiation in vitro lymphocytes with MN frequency in most cases must be acknowledged as normal. This distribution character points out that damage appearance in the individual (genomic instability) in a single lymphocytes increases the probability of the damage appearance in another lymphocytes. We can propose that damaged stem cells lymphocyte progenitor's exchange by information with undamaged cells--the type of the bystander effect process. It can also be supposed that transmission of damage to daughter cells occurs in the time of stem cells division.

[Adaptive response of blood lymphocytes as a marker of hemopoiesis status in exposed persons].

An obvious correlation between the type of reaction manifested by peripheral blood lymphocytes to low dose irradiation in vitro (adaptive potential), the RBM cell composition (during the period of the major exposure), and the peripheral blood cell composition (at a late time period coincident with the studies of induced radioresistance) has been found in the Techa riverside residents in the later periods after the onset of a long-term low-dose rate radiation exposure (55-60 years later) within a range of individual red bone marrow doses from 0.01 to 1.79 Gy. The nature of these dependences observed in chronically exposed individuals differs from that revealed in the controls. It can be suggested based on the results of the study that the capacity for the adaptive response shown by peripheral blood lymphocytes donated by exposed persons in the remote period after exposure can be regarded as a biological marker of the functional state of the hemopoietic stem cell pool.

[Principal inferences from studies of radiobiological effects for radiation protection purposes].

The most recent Recommendations (Publication 103) issued by the International Commission for Radiological Protection (ICRP) are based on the data that have been published since 1990 up to now. The basic task of the ICRP Committee 1 was to formulate the key implications of studies on radiobiological effects for the purposes of radiological protection. Presented in the paper are the new achievements in the field of biology, radiobiology and radiation epidemiology which were taken into account by the ICRP in the process of Publication 103 preparation. The Recommendations provide present-day values of weighting factors for radiation exposure and tissue weighting factors, as well as radiation detriment and radiogenic risk factors for cancer and genetic diseases. Also considered are tissue reactions to radiation exposure, consequences of in utero exposure and the risks of developing non-cancer diseases for exposed individuals. It should be noted that the key inferences and recommendations are to a considerable degree related to biological effects accounted for by acute and chronic exposure to ionizing radiation in the range of small doses (up to 100 mSv).

[Phytoplankton in reservoir R-11 of Techa reservoir cascade of Industrial Association "Maiak"].

Phytoplankton of reservoir R-11 was investigated at vegetative seasons of 2007 and 2008. R-11 is a locking reservoir in the cascade of Mayak PA reservoirs. The specific activity in water of R-11 ranged from 0.9 to 1.8 kBq/dm for 90Sr and from 0.98 to 3.97 kBq/dm3 for 137Cs; in bottom sediments it ranged from 20 to 400 kBq/kg for 90Sr and from 0.35 to 220 kBq/kg for 137Cs. Concentration of SO4- exceeded the maximum permissible concentration for fishing reservoirs in 5-7 times. The content of 90Sr in the phytoplankton has made 400 kBq/kg (for dry weight), and 137Cs--2.20 kBq/kg (for dry weight). The absorbed dose of irradiation for the phytoplankton calculated under the content of 137Cs and 90Sr in water and in phytoplankton (the external irradiation from activity of bottom sediments was not considered) has made 901 mGy per year. Altogether the phytoplankton of reservoir R-11 included 107 species. Such species of Cyanobacteriae as Oscillatoria agardhii Gom. was the dominant in phytoplanktonic community. Another Cyanobacteriae, Lyngbya limnetica Lemm. and Aphanizomenonflos-aquae (L.) Ralfs. acted the most important part in a complex of species-subdominants. According to quantitative development of the phytoplankton the reservoir R-11 can be classified as P-mezosaprobe waters.

[Carcinogenic risk in residents of the Techa riverside villages].

The paper summarizes carcinogenic risk estimates in residents of the Techa riverside villages who have been exposed for many years to radiation due to discharge of radioactive wastes from the Mayak Production Association into the Techa-Iset-Tobol-Ob river system. Analysis of cancer incidence and mortality data has shown a statistically significant dose-dependent increase in the risk of both malignant tumors and leukemia. The dependence of excess relative risk on exposure dose is well described by a linear model. No evidence has been obtained that carcinogenic risk resulting from low-rate radiation exposure is lower than that from acute exposure of A-bomb survivors. Difficulties of following up vital status due to population migration, incomplete data on mortality causes, and inaccurate dose estimates are believed to be key contributors to radiation risk uncertainties.

[Ecotoxicological value of sediments state from reservoir R-11 of Techa River reservoir cascade].

Researches of sediments state from reservoir R-11 of tandem Techa river reservoir cascade were made. Shershni (Shershni's reservoir, Chelyabinsk region) was used as reference reservoir. Radiochemical analysis of sediments and water from those reservoirs were made (radioactivity in sediments of R-11 ranged from 240 to 360 kBq/kg of dry weight for 90Sr and from 10 to 161 kBq/kg of dry weight for 137Cs). Hydrobiological researches were included (1) detection of quantitative progress and species composition of Oligochaeta fauna in reservoirs and (2) bioassay of sediments in laboratory conditions with using test-organisms Tubifex culture. Calculation of absorbed dose for Oligochaeta from reservoir R-11 was performed on basis of radiochemical analysis data. Our results indicated that quantitative progress of Oligochaeta in reservoir R-11 was less then progress in Shershni's reservoir. R-11 sediments bioassay did not show any toxic effect by tubificidae in laboratory experiments. Significant dependence for quantitative progress Oligochaeta in reservoir R-11, survival rate and breeding power from absorbed dose rate weren't found. However in subacute research breeding power for animals with higher radiation (absorbed) dose was reduced.

[The modification of radiation-induced immune response].

In the overview it is shown that immune response to ionizing radiation exposure is determined not only by dose and dose rate, as was believed earlier, but also by a complex of factors (individual's age at exposure, genetic status, etc.). The emphasis in the overview is made on analyses of factors of endogenous (antioxidants, cytokines, peptides, etc.) and exogenous nature which are capable of modifying immune response following radiation exposure.

[Tissue reactions under chronic exposure to ionizing radiation].

The overview presents an outline of the radiobiological mechanisms governing the origin of tissue reactions manifested by a number of systems influencing the course and the outcomes of chronic exposure of man. The issues under consideration include the key mechanisms of tissue reactions and adaptation in response to a long-term and fractionated exposure to ionizing radiation. The response of the hemopoietic, of immune, of genital, of endocrine, of respiratory systems and of the skin to chronic radiation is described. The development of a new approach to threshold dose estimation for chronic exposure effects is discussed.

[Some regularities in the behavior of radionuclides in water of the lakes situated on the East-Urals Radioactive Trace].

The paper presents the summary and the analysis of the results from a long-term monitoring of 90Sr specific activity in water of the lentic lakes Uruskul, L. Ighish, Kuyanysh and Travyanoye situated in Chelyabinsk Oblast on the East-Urals Radioactive Trace which was formed due to the 1957 accident at the Mayak PA. The data of measurements conducted over a 50-year period were approximated based on a function representing a sum of two (or three) exponents. The results of the analysis allowed us to study the peculiarities of reduction in the specific activity of 90Sr in the lakes of interest, and to obtain prognostic assessment of the development of the radioecological situation in these water reservoirs for the time period up to 2017. Presented in the paper are also data on the current levels of 90Sr and 137Cs specific activity in water of the lakes Uruskul, L. and S. Ighish, Kuyanysh, Travyanoye and Shablish. The estimates of the current reserves of these radionuclides are provided. Was shown that these lakes can be returned to the production use.

[Characterization of immunity status in exposed residents of the Techa riverside villages 50 years after the onset of radiation exposure].

The goal of the study was to assess the state of immunity in exposed residents of the Techa riverside villages 50 years, or more, after the onset of radiation exposure. 127 chronically exposed persons and 55 unexposed persons were studied. The mean dose to red bone marrow (RBM) was 0.69 Sv in exposed subjects, the mean dose to soft tissue was 0.07 Sv, the mean dose rate amounted to 0.10 Sv/yr to RBM and 0.02 Sv/yr to soft tissues in 1950. The state of the basic links of the immunity system (cellular, humoral, mononuclear phagocyte system, cytokine spectrum, etc.) was assessed using conventional methods. Exposed persons manifested a significant reduction in the absolute counts of CD3+, CD4+, CD 11b+, CD16+ lymphocytes in the peripheral blood, as well as an increase in the relative counts of CD8+. The group comprised of the Techa riverside residents demonstrated an increased immunoregulatory index (exposed individuals: 1.47; controls: 1.71, p = 0.001). An increased production of Immunoglobulin A and increased proportions of CD25+ lymphocytes were revealed in exposed individuals. Changes in the phagocytic activity of neutrophils and monocytes were insignificant, and were primarily associated with changes in the proportions of pagocytes in the peripheral blood stream. The state of the immunity in chronically exposed individuals at late time after the begin of exposure is characterized by a number of specific features reflected primarily on the cellular immunity. No relationship between immunity changes and accumulated exposure dose and dose rate were noted over the period of maximum radiation exposures (1950).

[The effects of chronic radiation exposure on the frequency of mutations at minisatellite DNA loci in residents of the Techa Riverside Villages].

The frequency of mutations at eight minisatellite DNA loci (B6.7, CEB1, CEB15, CEB25, CEB 36, MS1, MS31 and MS32) in peripheral blood cells were assessed for exposed residents of the Techa riverside villages as a function of individual exposure doses. The frequency of minisatellite mutations was found to be significantly higher in male gametes than in female ones; no clear-cut dose-effect relationship was traced. There was no evidence of dependence of mutation frequency on exposure dose rates in the year of conception, the offspring's intrauterine red bone marrow dose and soft tissues doses.

[The adaptive response of first generation offsprings irradiated parents].

In offspring's of first generation irradiated inhabitants of Techa river (fathers, mothers and both parents) the spontaneous level of damaged blood lymphocytes, sensitivity of lymphocytes to the additional acute irradiation in dose 1.0 Gy and radioinduced adaptive response after adaptive (5 cGy) and challenge (1.0 Gy) irradiation 5 h after was studied. The micronuclei test with cytochalasin B as a criteria of the effect have been used. It was shown, that descendents of irradiated parents differ from the control group. The main difference is the significant decrease of the adaptive response frequency in the progeny. In the offspring's of the irradiated fathers and mothers there is no one individuals with the adaptive response; in the offspring's of both irradiated parents the frequency of individuals with adaptive response decreases in control from 19.5% to 6.8%. The distribution of descendents according to response on adaptive irradiation differ significantly from the control distribution and from the each other. And the tendency to the radiosensitivity increase after adaptive irradiation was observed. In the whole joint group of progeny the mean spontaneous cell frequency with micronuclei decreased, but the sensitivity of lymphocytes to the additional acute irradiation doesn't differ from the control. The results of the paper permit to suppose that transgenerational genome instability in human can be determined. Earlier discovered decrease of the adaptive response frequency in the Techa river livings is observed in the offspring's of irradiated fathers, mothers and both parents.