Radiation-induced “bystander effects” were studied at the inter-organismal level. The experiment used mice irradiated at a dose of 3 Gy and nonirradiated bystander mice, kept together for 90 days. An analysis of the state of the bone marrow, spleen, and thymus in the experimental animals was carried out, which included an assessment of the mass of the spleen and thymus, as well as the number of nuclear cells in the bone marrow, spleen, and thymus in mice. The results of this study indicate the presence of a “bystander effect” in the nucleated cells of the bone marrow of mice. In unirradiated animals that were kept with irradiated mice in a cage without a septum, the number of nucleated cells is reduced statistically significantly ( t = 2.58; p = 0.02) compared to the control. There is an effect of increasing the number of nucleated cells in the bone marrow in the group of irradiated mice in a cage with a septum, statistically significant by 15% more than in the gamma control group ( t = 2.36; p = 0.03), i.e., the “rescue effect.” Obviously, in all organs of the hematopoietic system—bone marrow, thymus, and spleen—there are violations associated with the factor of contact of animals. It is possible that the observed radiation-induced “nontargeted effects” are realized at the level of induced changes in the DNA.
The task of studying radiation “bystander effects” at the organism level was set in the work. Irradiated and nonirradiated mice that were kept together were used in the experiment. Mice were irradiated at a dose of 3 Gy in a research radiobiological gamma installation with the sources of 137Cs. The number of leukocytes and relative number of lymphocytes in the peripheral blood of mice were estimated 3, 7, 14, 30, 60, and 90 days after the beginning of the experiment. In nonirradiated “bystander” mice kept with irradiated mice both in the cages without a partition and with a partition, there is a possible trend towards a decrease in the number of leukocytes as compared with indices in the biocontrol. During the analysis of relative number of lymphocytes, a trend towards a decrease in the index in “bystander” mice was demonstrated both when keeping without a partition and with a partition. In nonirradiated “bystander” animals when keeping with irradiated animals in the cage with a partition, a statistically significant decrease in the relative number of lymphocytes in the peripheral blood was registered on days 3 (t = 2.13; p = 0.047), 30 (t = 2.94; p = 0.01), and 90 (t = 3.07; p = 0.01) after irradiation as well as when keeping in the same cage with irradiated mice without a partition on day 60 (t = 2.24; p = 0.038) after the beginning of the experiment. A “bystander effect” in nonirradiated animals is one of possible explanations for the detected changes. In irradiated animals that were kept in the same cage with a partition together with nonirradiated animals, a statistically significant increase in the relative number of lymphocytes was registered on days 3 (t = 2.6; p = 0.02), 14 (t = 2.61; p = 0.018), and 60 (t = 2.38; p = 0.03) (“rescue effect”). Based on data obtained in the present experiment, it is assumed that the radiation “bystander effect” can have the opposite nature; that is, nonirradiated organisms are able to reduce the radiation effects in irradiated individuals (“rescue effect”).
NOD SCID mice were humanized by transplanting human hematopoietic cells isolated from umbilical cord blood. A dose-dependent death of hematopoietic cells and their subsequent recovery were shown after acute external γ-irradiation in the model of humanized mice. The proposed approach can be used for preclinical studies of radioprotective agents and for assessment of the impact of adverse factors on the survival rate and functional properties of human hematopoietic stem cells in vivo .
Assessment of individual responses of cells, tissues and the whole body to radiation exposure is an important challenge for radiobiology and radiation safety. The study was aimed to develop the method for estimation of the human hematopietic stem cell (HSC) individual response in the humanized mouse model. The cord blood or peripheral blood HSCs were administered to the NOD SCID immunodeficient mice. The number of maturing HSCs (CD34+ cells) and mature CD45+ leukocytes was assesed after the acute gamma exposure to the doses of 0.5 Gy, 1 Gy, and 1.5 Gy, along with the HSC share among all CD45low/+ cells within three days (period of maximum mortality) and 14 days (period of active restoration) after exposure. The relationship between the indicato values and the exposure dose was calculated by regression analysis. There was exponential relationship between the human HSC survival rate in humanized mice and the dose on day three after exposure (R2 = 0.93; F = 211; p < 0.01), while the relationship between the number of HSCs and the dose on day 14 after exposure was linear (R2 = 0.65; F = 12.9; p = 0.01). The C14/3 coefficient calculated as a ratio of the HSC share among all human CD45low/+ cells on day 14 after exposure to the same parameter on day three after exposure was proposed as an indicator of HSC mortality and HSC number restoration. C14/3 negatively correlated with the exposure dose (R2 = 0.57; F = 13.3; p = 0.004), it was higher in radioresistant mice and the model of cysteamine-induced radioresistance in humanized mice. The model mice humanized using the peripheral blood HSCs can be used to assess individual HSC response to acute external gamma exposure based on C14/3 and the data on the HSC survival and restoration.
In an experiment to study radiation "bystander effects" (BEs) at the interorganismic (systemic) level, we use mice irradiated at a dose of 3 Gy and mice that are not irradiated, bystanders, kept together. In the irradiated animals, on the 3rd and 60th days, when kept without a partition, and on the 14th day when kept in cells with and without a partition, a statistically significant decrease in the frequency of normal chromatophilic (oxyphilic) erythrocytes (NCEs) with micronuclei is revealed when compared with the gamma control. In the nonirradiated bystander-mice, kept with the irradiated mice in a cage with a partition on the 14th day and in a cage without a partition on the 60th day, a tendency to exceed the micronucleus (MN) frequency of the erythrocytes' values in the biocontrol is revealed. Based on the data obtained in this experiment, it is assumed that the radiation BE has the opposite character; i.e., nonirradiated organisms are able to reduce the radiation effects in irradiated individuals: the "rescue effect."
As a result of operation of the Mayak Production Association (Mayak PA), Chelyabinsk Oblast, Russia, an enterprise for production and separation of weapon-grade plutonium in the Soviet Union, ecosystems of a number of water bodies have been radioactively contaminated. The article presents information about the current state of ecosystems of 6 special industrial storage reservoirs of liquid radioactive waste from Mayak PA: reservoirs R-3, R-4, R-9, R-10, R-11 and R-17. At present the excess of the radionuclide content in the water of the studied reservoirs and comparison reservoirs (Shershnyovskoye and Beloyarskoye reservoirs) is 9 orders of magnitude for (90)Sr and (137)Cs, and 6 orders of magnitude for alpha-emitting radionuclides. According to the level of radioactive contamination, the reservoirs of the Mayak PA could be arranged in the ascending order as follows: R-11, R-10, R-4, R-3, R-17 and R-9. In 2007-2012 research of the status of the biocenoses of these reservoirs in terms of phytoplankton, zooplankton, bacterioplankton, zoobenthos, aquatic plants, ichthyofauna, avifauna parameters was performed. The conducted studies revealed decrease in species diversity in reservoirs with the highest levels of radioactive and chemical contamination. This article is an initial descriptive report on the status of the biocenoses of radioactively contaminated reservoirs of the Mayak PA, and is the first article in a series of publications devoted to the studies of the reaction of biocenoses of the fresh-water reservoirs of the Mayak PA to a combination of natural and man-made factors, including chronic radiation exposure.