Characteristic cytogenetic effects of small doses of ionizing radiation

A study was made of the frequency of chromosome aberrations in human lymphocyte culture after gamma-irradiation (60Co) with doses ranging from 0.05 to 1.0 Gy at dose--rates of 0,005, 0.05 and 0.5 Gy/min. The frequency of structural changes in chromosomes at low doses was higher than it was expected in the case of extrapolating the effect produced by high to low doses of radiation; within the dose range from 0.1 to 0.5 Gy a plateau was registered for aberrations of the exchange type (dicentrics and rings). The abnormal character of the dose dependence of the yield of chromosome aberrations persisted with all three dose - rates under study.     

Mathematical analysis of genetic effects of low doses of ionizing radiation

The comparative study of effects of low doses of radiation on peripheral blood lymphocytes of persons occupationally exposed to radiation and non-exposed ones was carried out. The main attention was paid to radio-adaptive response forming under consistent exposure to low (0.05 Gy) and damaging (2 Gy) doses of gamma-irradiation. Noticeable heterogeneity in capacity for adaptive response forming in occupational group was revealed. The mathematical model adequate to experimental material was constructed using Kohonen neuronets.     

Cytogenetic effects in children exposed to low doses of ionizing radiation

The obtained data indicate that frequencies of different types of cytogenetic anomalies in investigated children groups living in radionuclide contaminated territories and children irradiated in utero have complicated patterns. The frequency of chromosomal anomalies in the investigated groups of children exceeds the average population level. At the same time, no statistically significant differences in frequencies of various types aberrations between groups of children were revealed.     

The effects of low doses of low-intensity ionizing radiation on DNA structure and function

Chronic effects of low doses of low-intensity ionizing radiation (IR) on biological objects have gained great social significance. This has given a considerable impetus to research into the biological effects and mechanisms of such exposures, both in Russia and abroad. In this paper, an overview of the physicochemical and molecular basis of IR influence at low doses is provided. Means of cell protection from radiation damage are studied and an analysis of the typical features and differences in the radiation effects at low and high doses is carried out. We considered DNA radiation damage, both in cell cultures and in vivo, as well as the processes and results of their repair. Particular attention is paid to changes in the basic paradigms of biological radiation effects at low doses.     

Immunochemical determination of DNA damage induced by high doses of ionizing radiation

It was shown by the immunochemical method that DNA of X-irradiated E. coli cells of a radiosensitive mutant ABA88uvr A6 can react with the antiserum to thymine dimers which, in all appearance, are induced by ionizing radiation in bacterial DNA. The number of thymine dimers in DNA of E. coli AB1886uvr A6 increased with the dose increase. No dimers were detected in radioresistant cells of M. radioproteolyticus probably due to the effective excision thereof.     

Effect of ionizing radiation at high doses on the cyclic nucleotide content of the rat brain

The study of the rat brain after irradiation with superlethal doses of 100 and 500 Gy has revealed a decrease in the cAMP content at early times after exposure. The most considerable decline in the cGMP content was noted in the cerebellum and cerebral hemisphere cortex where low cGMP level was retained for 24 h following irradiation. It is suggested that the observed changes play an important role in the development of the CNS syndrome.     

Early effects of low doses of ionizing radiation on the fetal cerebral cortex in rats

Pregnant rats were exposed to gamma radiation from a 137Cs irradiator on gestational Day 15. Fetuses that received 0.25, 0.5, 0.75, or 1.0 Gy were examined 24 h after irradiation for changes in the cells of the cerebral mantle of the developing brain. The extent of changes following 0.5 Gy was studied at 3, 6, 12, or 24 h after exposure. Cortical thickness of the cerebral mantle was not significantly altered. The number of pyknotic cells, number of macrophages, nuclear area, and number of mitotic cells were altered in a dose-related way. The number of pyknotic cells was significantly increased at all doses. A positive correlation between the number of pyknotic cells and the number of macrophages developed with time. At 3 h after irradiation about 60% of pyknotic cells were found in the subventricular zone and about 25% in the intermediate zone and cortical plate. The number of such cells in the upper layers of the cortex steadily increased up to 24 h, at which time about 70% of pyknotic cells were in these two layers. The relationship of the movement of pyknotic cells to migration of postmitotic neuroblasts is discussed.     

Influence of mitotic delay on the results of biological dosimetry for high doses of ionizing radiation

The purpose of this study was to systematically investigate how high doses of sparsely and densely ionizing radiations influence the proliferation time of lymphocytes in short-term cultures and, consequently, the observed frequencies of dicentric and centric ring chromosomes. Peripheral blood samples from five volunteers were irradiated with high doses of 200 kV X-rays and with neutrons with a mean energy of <E _n>=2.1 MeV. First division metaphase cells were collected after different culture times of 48, 56, and 72 h and dicentrics, centric ring chromosomes, and acentric fragments were determined. The data hint at considerable mitotic delay. The main increase in the number of chromosome aberrations occurred between 48 and 72 h after an X-ray exposure and between 56 and 72 h after neutron exposure. When the data were used for a calibration of aberration frequency versus dose, subsequent dose estimations resulted, however, in comparable values. Thus, in spite of the influence of mitotic delay on observable chromosome aberrations, at least for the radiation types investigated here, a culture time of 48 h is acceptable for biological dosimetry.     

Influence of low doses of ionizing radiation on tenascin expression in hybridoma cell systems

One of the achievements of the modern radiation ecology is the preparation and application of stable eukariotic cell lines to solve various problems occurring under exposure to ionizing radiation, especially to low doses. The detection of onco-fetal protein--tenascin in different embryonic and tumor cells of humans and animals supposes the probability of appropriate gene expression in lymphoid cells, including hybridomal cells. Using the immunochemical method, the study of tenascin expression in two mouse hybridomal lines was carried out. Tenascin was revealed in hybridomal lines MLC-1 and K-48. Further hybridomal cell lines were exposed to X-ray radiation (120 KV) with doses 2.10,15 cGy. The obtained results demonstrated the sensitivity of tenascin expression to low doses of ionizing radiation, that may be used as a convenient model of studying of genotoxic effects of various damaging ionizing agents on a cell level.     

Effect of graded doses of ionizing radiation on the human testis

A portable unit was developed to provide uniform irradiation of the human testes. The device had built-in radiological protection and provided a dosage independent of the subject geometry, uniform to within +or- 5%. Single doses, between 8-600 rad were administered to the testes of human subjects. Observations were made both before and following irradiation. Parameters evaluated included sperm concentration, motility and morphology, seminal fluid volume, plasma and urinary gonadotropin and testosterone levels, urinary estrogens, and comparison of testicular biopsies taken before and after irradiation in the same subject. Dose-response relationships and recovery times were determined for each dose range studied.     

Brain beta-adrenergic and GABA-ergic receptors in rats after exposure to high doses of ionizing radiation

The radioactive ligands, [3H]dihydroalprenolol and [3H]muscimol, were used to estimate the condition of beta-adrenoreceptors of the brain cortex and GABA-receptors of the cerebellum during transient neurologic disorders caused by irradiation of rats with high-energy (20 MeV) electrons of 200 Gy. No significant changes were observed in the GABA-ergic brain system while the changes in beta-adrenoreceptors of the brain were pronounced and manifested by the loss by the receptors of their ability to bind the specific ligand, dihydroalprenolol. The changes observed were reversible and correlated with the development of neurologic disorders.     

The regulation of pollen tube growth in Douglas-fir following high doses of ionizing radiation

The relationship between temperature and sensitivity to gibberellin A₃ (GA₃) was studied in lettuce seedlings (Lactuca sativa L. cv. Arctic). Dose/response curves for hypocotyl elongation (10^-4 mol l^-1 to 10^-8 mol l^-1) were constructed for a range of temperatures and the slope of the linear portion of the plots used as an indication of the sensitivity to GA₃. Hypocotyls were unresponsive to GA₃ below 13°C but above this temperature sensitivity increased linearly. Plots of growth rate against temperature had inflexions between 12°C and 13°C, with slopes above this point which increased with increasing GA₃ concentration. The Q₁₀ value for response increased in a similar manner. Reaction rates of NAD-dependent malate dehydrogenase and peroxidase extracted from hypocotyls varied linearly with temperature whilst nonspecific tetrazolium reduction, a membrane based activity, showed an abrupt rate change above 14°C. Pre-exposure to GA₃ had no effect on the temperature responses of soluble or particulate enzymes.Abbreviation GA₃ gibberellin A₃     

Low doses and high doses of heparin have different effects on osteoblast-like Saos-2 cells in vitro

Long-term treatment with heparin has been associated with an increased risk of osteoporosis. Given the importance of heparan sulfate proteoglycans for bone metabolism, it can be anticipated that heparin due to its structural similarity with heparan sulfate chains somehow interferes with the biological activities of these cell surface- and extracellular matrix-associated molecules. Initially in order to study the effect(s) of heparin on osteoblasts that possibly contribute to the development of heparin-induced osteoporosis, we treated osteoblast-like Saos-2 cells in monolayer culture for different periods of time with different concentrations of heparin. None of the heparin concentrations tested led to an inhibition of osteoblast proliferation during the early proliferative phase. After longer incubation times, however, cultures treated with higher concentrations of heparin (>/=5 microg/ml) exhibited a reduction in cell number as well as an inhibition of matrix deposition and mineralization. These effects could not be observed with lower heparin concentrations. On the contrary, low concentrations of heparin (5-500 ng/ml) even promoted matrix deposition and its subsequent mineralization. Apparently, heparin has a biphasic effect on osteoblast-like Saos-2 cells, being inhibitory at high concentrations but stimulatory at low concentrations. These results imply that heparin at concentrations well below those used for antithrombotic therapy might eventually turn out to be beneficial for bone formation.     

Gene expression profiles of normal human fibroblasts after exposure to ionizing radiation: a comparative study of low and high doses

Several types of cellular responses to ionizing radiation, such as the adaptive response or the bystander effect, suggest that low-dose radiation may possess characteristics that distinguish it from its high-dose counterpart. Accumulated evidence also implies that the biological effects of low-dose and high-dose ionizing radiation are not linearly distributed. We have investigated, for the first time, global gene expression changes induced by ionizing radiation at doses as low as 2 cGy and have compared this to expression changes at 4 Gy. We applied cDNA microarray analyses to G1-arrested normal human skin fibroblasts subjected to X irradiation. Our data suggest that both qualitative and quantitative differences exist between gene expression profiles induced by 2 cGy and 4 Gy. The predominant functional groups responding to low-dose radiation are those involved in cell-cell signaling, signal transduction, development and DNA damage responses. At high dose, the responding genes are involved in apoptosis and cell proliferation. Interestingly, several genes, such as cytoskeleton components ANLN and KRT15 and cell-cell signaling genes GRAP2 and GPR51, were found to respond to low-dose radiation but not to high-dose radiation. Pathways that are specifically activated by low-dose radiation were also evident. These quantitative and qualitative differences in gene expression changes may help explain the non-linear correlation of biological effects of ionizing radiation from low dose to high dose.     

Pro-inflammatory cytokine expression of spleen dendritic cells in mouse toxoplasmosis

Dendritic cells have been known as a member of strong innate immune cells against infectious organelles. In this study, we evaluated the cytokine expression of splenic dendritic cells in chronic mouse toxoplasmosis by tissue cyst-forming Me49 strain and demonstrated the distribution of lymphoid dendritic cells by fluorescence-activated cell sorter (FACS). Pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6, and IL-10 increased rapidly at week 1 post-infection (PI) and peaked at week 3 PI. Serum IL-10 level followed the similar patterns. FACS analysis showed that the number of CD8α(+)/CD11c(+) splenic dendritic cells increased at week 1 and peaked at week 3 PI. In conclusion, mouse splenic dendritic cells showed early and rapid cytokine changes and may have important protective roles in early phases of murine toxoplasmosis.     

Effect of low doses of low-intensity ionizing radiation on the DNA structure and functions

Chronic effects of low doses of low intensity ionizing radiation (IR) on biological objects have now become of great social significance. This has given a considerable impetus to research into biological effects and mechanisms of such exposures both in Russia and abroad. This paper provides an overview of physicochemical and molecular bases of the IR influence at small doses and the ways of cell protection from the radiation damage, as well as the analysis of characteristic features and differences in the effects of radiation at small and high doses. We consider the DNA radiation damage both in cell cultures and in vivo, as well as processes and results of their repair. Particular attention is paid to the changes in the basic paradigms of radiation biological effects of small doses.     

Pseudonormal thymocytes--a unique reaction of the lymphoid elements of the thymic cortex to high doses of ionizing radiation

The method of electron microscopy was used to study the phenomenon of "paradoxical resistance" of thymocytes to very high radiation doses (40 and 200 Gy). The formation of "pseudonormal" thymocytes, which represented a peculiar form of radiation death of these cells, was shown to be a function of radiation dose and time after irradiation.     

Membrane effects of ionizing radiation and hyperthermia

Results of numerous studies demonstrate that membranes are important sites of cell damage by both ionizing radiation and hyperthermia. Modification of membrane properties (mainly lipid fluidity) affects the cellular responses to radiation and hyperthermia but former concepts that membrane rigidification sensitizes cells to radiation while membrane fluidization potentiates hyperthermic damage have now been seriously challenged. It seems that the effects of membrane fluidity on cell responses to hyperthermia and radiation are due to an indirect influence on functional membrane proteins. The major role of lipid peroxidation in radiation damage to membranes has also been questioned. The existing evidence makes it unlikely that the interaction between radiation and hyperthermia is determined by the action of both agents on the same membrane components.