Dynamics and ecological-genetic variability of cytogenetic disturbances in Scots pine populations experiencing technogenic impact

Scots pine (Pinus sylvestris L.) populations in the vicinity of nuclear industry facilities were monitored. Aberrant cells occurrence in root meristem of germinated seeds from the impacted pine populations was found to be significantly above the reference level during all six years of observations. In the reference population, changes of cytogenetic disturbances with time appeared to be cyclic while in the impacted populations, technogenic stress was strong enough to destroy the natural regularities. The increase in cytogenetic disturbances was accompanied by growth of fluctuations magnitude; deviations of basic oscillation parameters from the reference values rose along with technogenic impact level. Variability in cytogenetic response increased under technogenic stress. Inter-family component of variability predominated, though its contribution slightly decreased in impacted populations. A tendency for destabilization of a repetition coefficient dynamics was found under technogenic impact. A portion of the seeds was exposed to 15 Gy of gamma-rays, and higher radio-resistance in the impacted populations was observed. In the reference population, a family-related analysis of cytogenetic variability components after acute y-exposure revealed significant contributions of "family" and "germination conditions" factors as well as their interactions. On the contrary, in populations existing under chronic stress, considerable modifications in the structure of ecological-genetic variability were found, their degree increasing with technogenic impact severity.     

Clinical and epidemiological analysis of possibility of acute myocardial infarction development in personnel of radiation dangerous plants

According to the data of cohort and to the "case-control" studies, dynamics of an acute myocardial infarction (AMI) morbidity during the period 1998-2002 and role of radiation factor in AMI development among personnel of radiation dangerous plants (by the example of Siberian Group of Chemical Enterprises (SGCE) exposed to a long-term impact of ionizing radiation in the range of "low" doses) were being carried out. It was determined that in personnel of the main production (working in contact with IR sources) the gradient increase of AMI morbidity was registered during the study period. Personnel of the main production in comparison to personnel of support production (correlating age, sex and examination level) have statistically significant increase of standardized relative risk coefficients of AMI development. When evaluating standardized relative risk coefficient depending on the cumulative dose of external y-radiation, it was impossible to determine the reliance between the rate of increase of radiation dose and standardized relative risk coefficient. According to logistic regression, was determined that individual features of dose load formation are of great significance in AMI development for the personnel of the main production. Absolute values of standardized regression coefficients peculiar to the values characterizing technogenic impact, exceed correspondent values for "traditional" risk factors to be the components of the regression equation, two-three times as much. The combination of these factors allowed to prognosticate AMI development in 94.3% cases. Obtained data made possible to conclude that in pathogenesis of acute coronary diseases ionizing radiation acts as a factor that aggravate negative influence of "traditional" risk factors of cardio-vascular diseases through pleiotropic effects.     

Genetic efficacy of low doses of ionizing radiation in chronically-irradiated small mammals

Earlier we have established the genetic effects of low dose chronic irradiation in bank vole (somatic and germ cells, embryos), in pond carp (fertilized eggs, embryos, fry) and in laboratory mice (somatic and germ cells) in the range of doses from near-background to 10 cGy. These low dose effects observed in mammals and fish are not expected from extrapolation of high dose experiments. For understanding reasons this discrepancy the comparative analysis of genetic efficiency of low dose chronic irradiation and the higher doses of acute irradiation was carried out with natural populations of bank vole which inhabited the two sites differing in ground of radionuclide deposition. For comparing efficiency the linear regression model of dose-effect curve was used. Dose-effect equations were obtained for animals from two chronically irradiated bank vole populations. The mean population absorbed doses were in the range 0.04-0.68 cGy, the main part of absorbed doses consisted of external radiation of animals exposed to 137Cs gamma-rays. Dose-effect equations for acute irradiation to 137Cs gamma-rays (10-100 cGy) were determined for the same populations. Comparison of genetic efficiency was made by extrapolation, using regression coefficient beta and doubling dose estimation. For chronic exposure the doubling doses calculated from low-dose experiments are 0.1-2 cGy and the doubling doses determined from high-dose experiments are in the range of 5-20 cGy. Our hypothesis that the doubling dose estimate is calculated in higher-dose ionizing radiation experiments should be much higher than the deduced from the low dose line regression equation was verified. The doubling dose estimates for somatic cells of bank vole and those for germ cells of laboratory mice are in close agreement. The radiosensitivity of bank vole chromosomes were shown is practically the same as that for human lymphocytes since doubling dose estimates for acute irradiation close to each other. For low LET radiation a higher genetic efficiency of chronic low doses in comparison with the higher doses of acute gamma-irradiation (137Cs source) was proved by three methods.     

Repeated small perturbation approach reveals transcriptomic steady states

The study of biological systems dynamics requires elucidation of the transitions of steady states. A "small perturbation" approach can provide important information on the "steady state" of a biological system. In our experiments, small perturbations were generated by applying a series of repeating small doses of ultraviolet radiation to a human keratinocyte cell line, HaCaT. The biological response was assessed by monitoring the gene expression profiles using cDNA microarrays. Repeated small doses (10 J/m2) of ultraviolet B (UVB) exposure modulated the expression profiles of two groups of genes in opposite directions. The genes that were up-regulated have functions mainly associated with anti-proliferation/anti-mitogenesis/apoptosis, and the genes that were down-regulated were mainly related to proliferation/mitogenesis/anti-apoptosis. For both groups of genes, repetition of the small doses of UVB caused an immediate response followed by relaxation between successive small perturbations. This cyclic pattern was suppressed when large doses (233 or 582.5 J/m2) of UVB were applied. Our method and results contribute to a foundation for computational systems biology, which implicitly uses the concept of steady state.     

Possible Relationships between Plasma Glutathione Levels and Cytogenetic Indices in Peripheral Blood Lymphocytes of Children Exposed to Low Doses of Radiation

An analysis of correlations between cytogenetic indices in lymphocytes and levels of reduced glutathione in the plasma of peripheral blood in children born after the Chernobyl accident is presented. The studied systems in the child population demonstrated different responses to low-level radiation of their mothers living in conditions of radionuclide contamination (1–20 Ci/km² of ¹³⁷Cs). Low doses of radiation accumulated by mothers (below 30 cSv) proved to have a more pronounced effect on the studied systems in children as compared to high doses (from 30 to 60 cSv).     

Effects of radiation-ecological conditions and experimental hyperthyroid states on indicators of testis and prostate androgen receptors in rats

Dose-dependent changes of the molecular characteristics on androgen receptor (AR) systems in gonads of male rats were studied at experimental L-thyroxine-induced states after low doses irradiation exposures in different reference points of 10-km Chernobyl zone. The data obtained suggest a generalized working mechanism of "oscillatorous changes" for contents, affinities and cooperative properties of AR to its natural ligands as a "mirror" reflecting some adaptational reactions in target cells that modulates their androgen-controlled biochemical activity.     

Assessment of the Annual Additional Effective Doses amongst Minamisoma Children during the Second Year after the Fukushima Daiichi Nuclear Power Plant Disaster

An assessment of the external and internal radiation exposure levels, which includes calculation of effective doses from chronic radiation exposure and assessment of long-term radiation-related health risks, has become mandatory for residents living near the nuclear power plant in Fukushima, Japan. Data for all primary and secondary children in Minamisoma who participated in both external and internal screening programs were employed to assess the annual additional effective dose acquired due to the Fukushima Daiichi nuclear power plant disaster. In total, 881 children took part in both internal and external radiation exposure screening programs between 1^st April 2012 to 31^st March 2013. The level of additional effective doses ranged from 0.025 to 3.49 mSv/year with the median of 0.70 mSv/year. While 99.7% of the children (n = 878) were not detected with internal contamination, 90.3% of the additional effective doses was the result of external radiation exposure. This finding is relatively consistent with the doses estimated by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). The present study showed that the level of annual additional effective doses among children in Minamisoma has been low, even after the inter-individual differences were taken into account. The dose from internal radiation exposure was negligible presumably due to the success of contaminated food control.     

Life shortening in mice exposed to fission neutrons and gamma rays. VI. Studies with the white-footed mouse, Peromyscus leucopus

Some of the studies on late effects of neutron and gamma radiation previously carried out with the C57BL6 X BALB/c F1 hybrids of Mus musculus have been repeated with the white-footed mouse, Peromyscus leucopus, a cricetid rodent of a different subfamily, with differing physiological characteristics and a different spectrum of pathologies. Among the more important findings were the following: For both species, the life shortening per rad at low doses of either radiation was the same percentage of the life span. The limiting values of the relative biological effectiveness for life shortening from all causes of death were about the same for the two species, ranging from 8 to 16, depending on the method of calculation. Fractionated neutron exposures failed to produce significant life shortening in Peromyscus over that observed at single doses. Tumor-related deaths accounted for at least 70 to 75% of the radiation-specific excess mortality in Peromyscus.     

Abnormalities of embryonal development of vertebrates under the conditions of technogenic environmental pollution

The performed investigations have revealed 21 kinds of pathologies in the embryonal development of amphibia and more than 30 kinds in small mammals in the territories with radiation-chemical environmental pollution. Differences in embryonal mortality and pathologies of embryogenesis have been demonstrated for both the representatives of amphibia and mammals and within one class in the regions with different technogenic load. Embryonàl death and pathologies of embryonal development are considered as important reasons of reproductive losses for different species.     

The action of atomic radiation in low doses on the biota

The radiobiological studies carried out in conditions of lower and slightly increased natural radiation background have prompted an idea of "low doses" in radiobiology which is proposed for discussion. The author emphasizes that the difference between the leading molecular and cellular mechanisms that come into play under the effect of high- and low-level atomic radiation makes it incorrect to assess the risk from low radiation doses on the basis of the regularities obtained with high doses.     

Relationship between radiation-induced low-dose hypersensitivity and the bystander effect

Recent advances in our knowledge of the biological effects of low doses of ionizing radiation have shown two unexpected phenomena: a "bystander effect" that can be demonstrated at low doses as a transferable factor(s) causing radiobiological effects in unexposed cells, and low-dose hyper-radiosensitivity and increased radioresistance that can be demonstrated collectively as a change in the dose-effect relationship, occurring around 0.5-1 Gy of low-LET radiation. In both cases, the effect of very low doses is greater than would be predicted by conventional DNA strand break/repair-based radiobiology. This paper addresses the question of whether the two phenomena have similar or exclusive mechanisms. Cells of 13 cell lines were tested using established protocols for expression of both hyper-radiosensitivity/increased radioresistance and a bystander response. Both were measured using clonogenicity as an end point. The results showed considerable variation in the expression of both phenomena and suggested that cell lines with a large bystander effect do not show hyper-radiosensitivity. The reverse was also true. This inverse relationship was not clearly related to the TP53 status or malignancy of the cell line. There was an indication that cell lines that have a radiation dose-response curve with a wide shoulder show hyper-radiosensitivity/increased radioresistance and no bystander effect. The results may suggest new approaches to understanding the factors that control cell death or the sectoring of survival at low radiation doses.     

Rotavirus Surveillance at a WHO-Coordinated Invasive Bacterial Disease Surveillance Site in Bangladesh: A Feasibility Study to Integrate Two Surveillance Systems

The World Health Organization (WHO) currently coordinates rotavirus diarrhea and invasive bacterial disease (IBD) surveillance at 178 sentinel sites in 60 countries. However, only 78 sites participate in both surveillance systems using a common sentinel site. Here, we explored the feasibility of extending a WHO-IBD surveillance platform to generate data on the burden of rotaviral diarrhea and its epidemiological characteristics to prepare the countries to measure the impact of rotaviral vaccine. A six-month (July to December, 2012) surveillance, managed by IBD team, collected stool samples and clinical data from under-five children with acute watery diarrhea at an IBD sentinel site. Samples were tested for rotavirus antigen by ELISA and genotyped by PCR at the regional reference laboratory (RRL). Specimens were collected from 79% (n = 297) of eligible cases (n = 375); 100% of which were tested for rotavirus by ELISA and 54% (159/297) of them were positive. At RRL, all the cases were confirmed by PCR and genotyped (99%; 158/159). The typing results revealed the predominance of G12 (40%; 64/159) genotype, followed by G1 (31%; 50/159) and G9 (19%; 31/159). All in all, this exploratory surveillance collected the desired demographic and epidemiological data and achieved almost all the benchmark indicators of WHO, starting from enrollment number to quality assurance through a number of case detection, collection, and testing of specimens and genotyping of strains at RRL. The success of this WHO-IBD site in achieving these benchmark indicators of WHO can be used by WHO as a proof-of-concept for considering integration of rotavirus surveillance with WHO-IBD platforms, specifically in countries with well performing IBD site and no ongoing rotavirus surveillance.     

Severe trauma rate during planet geomagnetic storms

The growth of the diurnal frequency of appearance of heavy traumas during planetary geomagnetic storms is shown and statistically justified. No effect of short-term geomagnetic disturbances of natural and technogenic nature on the occurrence of acute mental and cardiovascular pathologies was detected on the basis of diurnal data.     

The study of the multifactorial anthropogenic effect on the ecosystems of the industrial reservoirs of "Maiak" industrial complex

The analysis of the ecological situation of the Southern Urals industrial water reservoirs of the nuclear fuel cycle enterprise, "Mayak" PA is represented. The study was held in the 80s - early 90s. The subjects of the study were: a cooling water reservoir--Kysyl-Tash Lake (R-2) as well as a radioactive waste storage reservoir (R-10). Irtyash Lake, which is a drinking water reservoir for the city of Ozyorsk and Alabuga and Kazhakul Lakes, located on the boundary of the Eastern Urals Radioactive Trace (EURT), were taken as control ones. Such water reservoirs as Irtyash, Kysyl-Tash and the waste storage reservoir (R-10) are incorporated into the Techa River basin; while Alabuga and Kazhakul Lakes are related to the interfluve between the Techa River and the Sinara River. The complex effect from such man--caused factors as radiation, chemical and thermal to water reservoirs' ecosystems was studied. Radionuclide specific activities of the major reservoir components (water, bottom sediments, and biological objects), cumulative stock and radiation doses to the biota were determined. Assessment of the condition of biological structures of individual reservoirs was performed. It was found that the long-term complex influence of radiation, thermal and chemical factors resulted in the formation of the unique technology-induced ecosystems being a part of "Mayak" PA process cycle. Radiation doses to the fish of the cooling water reservoir and the radioactive waste storage reservoir were experimentally estimated. These doses from the incorporated beta-emitters were not less then 2-3 Gy/year. The long-term complex influence of radiation and chemical factors didn't cause any irreversible changes either in the fish population or in the ecosystem. Water purity indicators like crayfish (Astacus leptodactilus Esch) and mollusk (Anodonta cygnea L.) were found in the cooling water reservoir. The comparative analysis of the ecological situation of the reservoirs carried out on the basis of several qualitative indicators and with the help of the formalized scoring system allowed determining that the optimum ecological conditions can be observed in Irtyash Lake. The quality of the environment of Alabuga Lake is slightly lower. The ecological conditions in Kysyl-Tash Lake are up to the standard, while in Kazhakul Lake they are lower than the standard. This is the result of the natural salinization of the ecosystem. The lowest indicator was obtained for the radioactive waste storage reservoir.     

"Either-or" two-slit interference: stable coherent propagation of individual photons through separate slits

In quantum theory, nothing that is observable, be it physical, chemical, or biological, is separable from the observer. Furthermore, ". all possible knowledge concerning that object is given by its wave function" (Wigner, E. 1967. Symmetries and Reflections. Indiana University Press, Bloomington, IN), which can only describe probabilities of future events. In physical systems, quantum mechanical probabilistic events that are microscopic must, in turn, account for macroscopic events that are associated with a greater degree of certainty. In biological systems, probabilistic statistical mechanical events, such as secretion of microscopic synaptic vesicles, must account for macroscopic postsynaptic potentials; probabilistic single-channel events sum to produce a macroscopic ionic current across a cell membrane; and bleaching of rhodopsin molecules (responsible for quantal potential "bumps") produces a photoreceptor generator potential. Among physical systems, a paradigmatic example of how quantum theory applies to the observation of events concerns the interactions of particles (e.g., photons, electrons) with the two-slit apparatus to generate an interference pattern from a single common light source. For two-slit systems that use two independent laser sources with brief (<1 ms) intervals of mutual coherence (Paul, H. 1986. Rev. Modern Phys. 58:209-231), each photon has been considered to arise from both beams and has a probability amplitude to pass through each of the two slits. Here, a single laser source two-slit interference system was constructed so that each photon has a probability amplitude to pass through only one or the other, but not both slits. Furthermore, all photons passing through one slit could be distinguished from all photons passing through the other slit before their passage. This "either-or" system produced a stable interference pattern indistinguishable from the interference produced when both slits were accessible to each photon. Because this system excludes the interaction of one photon with both slits, phase correlation of photon movements derives from the "entanglement" of all photon wave functions due to their dependence on a common laser source. Because a laser source (as well as Young's original point source) will have stable time-averaged spatial coherence even at low intensities, the "either-or" two-slit interference can result from distinct individual photons passing one at a time through one or the other slit-rather than wave-like behavior of individual photons. In this manner, single, successive photons passing through separate slits will assemble over time in phase-correlated wave distributions that converge in regions of low and high probability.     

Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation

Background

High doses of ionizing radiation result in biological damage; however, the precise relationships between long-term health effects, including cancer, and low-dose exposures remain poorly understood and are currently extrapolated using high-dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose-dependent responses to radiation.

Principal Findings

We have identified 7117 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts 1 h post-exposure. Semi-quantitative label-free analyses were performed to identify phosphopeptides that are apparently altered by radiation exposure. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation-responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatic analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role for MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation.

Conclusions

Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provide a basis for the systems-level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at different radiation doses and elucidate the impact of low-dose radiation exposure on human health.     

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.     

Radiobiology and the lessons of Chernobyl

The Chernobyl accident has marked the beginning of a new stage of radiobiology development and revealed scantiness of old concepts. One should (1) search for effective protectors against the long-term influence of low-level radiation and means of removal of radionuclides using criteria that differ principally from those used previously in selecting among nontoxic antioxidants, immunomodulators, and adaptogens; (2) study systematically the synergism of low doses of harmful agents and review the hygienic standardization system with due regard for the risk from their combinations; (3) consider comprehensively, on the basis of the experimental and clinical experience, the problem of "hot" particles and remote consequences of their influence on the respiratory and digestive systems; (4) study independently the problem of chronic stress as a combination of radiation effects and psycho-emotional consequences of the accident and living in the exposed areas; (5) consider it inadmissible to include in the B category the population of the districts influenced by the accident and to use the concept: "35 rads during the lifetime" in standardizing the radiation load; (6) organize a comprehensive analysis of the Chernobyl accident consequences for public health within the contaminated areas as well as for animals and plants using a single approved methodology and programme, the principle of "other equal conditions" being provided.