Gene expression profile of human lymphocytes exposed to (211)At alpha particles.

In this study, the Whole Human Genome 44K DNA microarray assay was used for the first time to obtain gene expression profiles in human peripheral blood lymphocytes 2 h after exposure (in suspension) to 6.78 MeV mean energy alpha particles from extracellular (211)At. Lymphocytes were exposed to fluences of 0.3-9.6 x 10(6) alpha particles/cm(2) [corresponding to mean absorbed alpha-particle doses (D(alpha)) of 0.05-1.60 Gy] over 30 min. Significantly modulated expression was identified in 338 early-response genes. Up-regulated expression was evident in 183 early-response genes, while the remaining 155 were down-regulated. Over half of the up-regulated genes and 40% of the down-regulated genes had a known biological process related primarily to cell growth and maintenance and cell communication. Genes associated with cell death were found only in the up-regulated genes and those with development only in the down-regulated genes. Eight selected early-response genes that displayed a sustained up- or down-regulation (CD36, HSPA2, MS4A6A, NFIL3, IL1F9, IRX5, RASL11B and SULT1B1) were further validated in alpha-particle-irradiated lymphocytes of two human individuals using the TaqMan(R) RT-qPCR technique. The results confirmed the observed microarray gene expression patterns. The expression modulation profiles of IL1F9, IRX5, RASL11B and SULT1B1 genes demonstrated similar trends in the two individuals studied. However, no significant linear correlation between increasing relative gene expression and the alpha-particle dose was evident. The results suggest the possibility that a panel of genes that react to alpha-particle radiation does exist and that they merit further study in a greater number of individuals to determine their possible value regarding alpha-particle biodosimetry.

Cosmic rays: a review for astrobiologists.

Cosmic rays represent one of the most fascinating research themes in modern astronomy and physics. Significant progress is being made toward an understanding of the astrophysics of the sources of cosmic rays and the physics of interactions in the ultrahigh-energy range. This is possible because several new experiments in these areas have been initiated. Cosmic rays may hold answers to a great number of fundamental questions, but they also shape our natural habitat and influence the radiation environment of our planet Earth. The importance of the study of cosmic rays has been acknowledged in many fields, including space weather science and astrobiology. Here, we concentrate on the astrobiological aspects of cosmic rays with regard to the enormous amount of new data available, some of which may, in fact, improve our knowledge about the radiation of cosmic origin on Earth. We focus on fluxes arriving at Earth and doses received, and will guide the reader through the wealth of scientific literature on cosmic rays. We have prepared a concise and self-contained source of data and recipes useful for performing interdisciplinary research in cosmic rays and their effects on life on Earth.

Discovering functional novelty in metagenomes: examples from light-mediated processes.

The emerging coverage of diverse habitats by metagenomic shotgun data opens new avenues of discovering functional novelty using computational tools. Here, we apply three different concepts for predicting novel functions within light-mediated microbial pathways in five diverse environments. Using phylogenetic approaches, we discovered two novel deep-branching subfamilies of photolyases (involved in light-mediated repair) distributed abundantly in high-UV environments. Using neighborhood approaches, we were able to assign seven novel functional partners in luciferase synthesis, nitrogen metabolism, and quorum sensing to BLUF domain-containing proteins (involved in light sensing). Finally, by domain analysis, for RcaE proteins (involved in chromatic adaptation), we predict 16 novel domain architectures that indicate novel functionalities in habitats with little or no light. Quantification of protein abundance in the various environments supports our findings that bacteria utilize light for sensing, repair, and adaptation far more widely than previously thought. While the discoveries illustrate the opportunities in function discovery, we also discuss the immense conceptual and practical challenges that come along with this new type of data.

[The parameters of genetic variability and of selection in offsprings of exposed humans].

Mayak workers offsprings parameters of genetic variability including heterozygosity, genetic combinations, quantitative characteristics of genetic class reproduction, genetic identity and intervals, and parameters of selection including relative adaptation of genetic classes and mean adaptation depending on preconceptive doses of parents' exposure were studied. Genetic markers of Mayak workers, their children and grandchildren were defined. Children whose parents had preconceptive doses of more than 200 cGy in comparison with the control group had the heterozygosity reduction by Hp system and tendency to the mean heterozygosity reduction studied genetic system. Also they had modifications in the frequency of combinations of separate genotypes and blood groups, genetic identity reduction and genetic interval increasing, increasing of the mean adaptation and reduction of the mean coefficient of selection by genetic system of Hp. Consequently the children of workers, preconceptively exposed to gamma-radiation in doses over 200 cGy, are susceptive to the gametic selection on system of Hp that realizes at their conception. In grandchildren, whose grandparents had preconceptive doses over 200 cGy, no changes in genotype Hp distribution were detected compared to controls. The absence of changes in genotype Hp distribution in workers' grandchildren is accounted for the absence of increased preconceptive exposure doses of their parents (F1-children), as well as for their marriages to the individuals (in 94.3% of cases), whose parents didn't have high (over 200 cGy) preconceptive exposure doses.

Gene expression signatures that predict radiation exposure in mice and humans.

BACKGROUND: The capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation. METHODS AND FINDINGS: We have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated samples with an accuracy of 90%, sensitivity of 85%, and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and nonirradiated human patients with an accuracy of 77%, sensitivity of 82%, and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated that are highly predictive of different levels of radiation exposure in mice and humans. CONCLUSIONS: We suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure.

Health effects resulting from the Chernobyl accident.

This article reviews the health effects of the Chernobyl accident. The clearest effect to be seen to date is the dramatic increase in thyroid cancer in children. The evidence for increased leukaemia is less clear, but there are indications of increased leukaemia incidence in Russian clean-up workers. There is also evidence of increases in breast cancer, cataract and cardiovascular disease. However, to date the largest public health problem caused by the accident is the mental health impact.

Cosmic ray impact on extrasolar earth-like planets in close-in habitable zones.

Because of their different origins, cosmic rays can be subdivided into galactic cosmic rays and solar/stellar cosmic rays. The flux of cosmic rays to planetary surfaces is mainly determined by two planetary parameters: the atmospheric density and the strength of the internal magnetic moment. If a planet exhibits an extended magnetosphere, its surface will be protected from high-energy cosmic ray particles. We show that close-in extrasolar planets in the habitable zone of M stars are synchronously rotating with their host star because of the tidal interaction. For gravitationally locked planets the rotation period is equal to the orbital period, which is much longer than the rotation period expected for planets not subject to tidal locking. This results in a relatively small magnetic moment. We found that an Earth-like extrasolar planet, tidally locked in an orbit of 0.2 AU around an M star of 0.5 solar masses, has a rotation rate of 2% of that of the Earth. This results in a magnetic moment of less than 15% of the Earth's current magnetic moment. Therefore, close-in extrasolar planets seem not to be protected by extended Earth-like magnetospheres, and cosmic rays can reach almost the whole surface area of the upper atmosphere. Primary cosmic ray particles that interact with the atmosphere generate secondary energetic particles, a so-called cosmic ray shower. Some of the secondary particles can reach the surface of terrestrial planets when the surface pressure of the atmosphere is on the order of 1 bar or less. We propose that, depending on atmospheric pressure, biological systems on the surface of Earth-like extrasolar planets at close-in orbital distances can be strongly influenced by secondary cosmic rays.

Identification of novel electroconvulsive shock-induced and activity-dependent genes in the rat brain.

Electroconvulsive shock (ECS) has been used as an effective treatment for patients suffering from major depression disorders and schizophrenia. However, the exact mechanisms underlying the action of ECS are poorly understood. Using high-density oligonucleotide microarrays, we identified 60 ECS-induced genes whose gene products are involved in the neuronal signaling, neuritogenesis and tissue remodeling. In situ hybridization and depolarization-dependent expression assay were performed to characterize 4 genes (lysyl oxidase, Ab1-046, SOX11, and T-type calcium channel 1G subunit) which have not yet been reported to be induced by ECS. Interestingly, the induction of these genes was observed mainly in the dentate gyrus of hippocampal formation and piriform cortex, where ECS-induced neural activation is highlighted, and depolarization of cultured cortical neurons also induced the expression of these genes. Taken together, our results suggest that therapeutic actions of ECS may be manifested by the activity-dependent induction of genes related to the plastic changes of the brain such as neuronal signaling neuritogenesis, and tissue remodeling.

Eugenol as an in vivo radioprotective agent.

In the present work, an attempt has been made to evaluate the possible in vivo radioprotection by eugenol. Swiss albino mice were administered different doses of eugenol (75,150 and 300 mg/kg) before exposure to 1.5 Gy of gamma radiation. The micronucleus test was carried out to determine the genetic damage in bone marrow. Our results demonstrated significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) with all three eugenol doses. Eugenol (150 mg/kg) was also tested against different doses of radiation (0.5, 1, 1.5, and 2 Gy) and was found to afford significant radioprotection. Reduction in the incidence of MnPCEs could be noticed up to 72 h postirradiation (1.5 Gy). Moreover, the level of peroxidative damage and the specific activities of lactate dehydrogenase (LDH) and methylglyoxalase I (Gly I) were observed in the liver of mice treated with eugenol for seven days in comparison to untreated mice. The results revealed that eugenol exerted significant protection against oxidative stress. This possibility was further supported by the enhanced response of Gly I and the lowered activity of LDH. The present findings suggested that eugenol has a radioprotective potential.

Implications of systemic malignancies on human fertility.

Cancer patients have now longer life expectancy due to improved treatment modalities. As the mortality rate decreased and the survival rate increased, the consequences of cancer treatment in terms of impaired fertility became more frequently encountered. The objective of this review is to highlight fertility issues associated with systemic malignancies. Systemic malignancies lead to deterioration of human fertility directly or indirectly as a result of cytotoxic treatment regimens. A variety of measures may be used to decrease the incidence of fertility decline that occurs. Gamete cryopreservation represents a widely accepted method for fertility preservation in cancer patients. In addition, other procedures such as germ cell transplantation and ovarian cryopreservation, which are currently being developed, are expected to make significant contribution in these cases. However, there are some ethical issues that should be considered before offering patients any of these options.

Autosomal mutation in somatic cells of the mouse.

Tumor suppressor genes are located on autosomal chromosomes. Therefore, an understanding of how cancer-related mutations occur in somatic cells requires a detailed understanding of spontaneous and induced autosomal mutagenesis. This review will present recent advances in the study of how autosomal mutations form in somatic cells by focusing on the mouse Aprt and Tk model systems that have been developed to examine the formation of autosomal mutations in vivo. These loci can detect the entire spectrum of mutations known to inactivate tumor suppressor genes. Studies with these models have provided novel information on the frequencies and types of spontaneous autosomal mutations that occur in different cell types. They also show great promise for the screening of genotoxic effects resulting from environmental exposures and for the study of mutation when DNA repair pathways are compromised. Continued use of the mouse Aprt and Tk models will have a significant impact on our understanding of some of the earliest steps in the conversion of normal cells to those with malignant phenotypes.

Analysis of the gene encoding copper/zinc superoxide dismutase homolog in Dictyostelium discoideum.

SodD, a Cu/Zn superoxide dismutase in Dictyostelium discoideum, shows 48% identity to the cytosolic Cu/Zn superoxide dismutase (SOD) of Saccharomyces cerevisiae (SOD1). The sodD gene is expressed in D. discoideum cells at late-developmental stages. However, gene expression was not detected in the sporeless mutant, indicating that sodD is a spore cell-specific gene. The D. discoideum mutant, in which sodD was disrupted, grew and formed a multicellular structure normally, therefore the gene is not essential for growth and development. The mutant spores were sensitive to UV-light compared to the wild-type spores, indicating that SodD protects spores from cellular damage caused by UV-light.

Radiation Research Society. 1952-2002. Historical and current highlights in radiation biology: has anything important been learned by irradiating cells?

Around 30 years ago, a very prominent molecular biologist confidently proclaimed that nothing of fundamental importance has ever been learned by irradiating cells! The poor man obviously did not know about discoveries such as DNA repair, mutagenesis, connections between mutagenesis and carcinogenesis, genomic instability, transposable genetic elements, cell cycle checkpoints, or lines of evidence historically linking the genetic material with nucleic acids, or origins of the subject of oxidative stress in organisms, to name a few things of fundamental importance learned by irradiating cells that were well known even at that time. Early radiation studies were, quite naturally, phenomenological. They led to the realization that radiations could cause pronounced biological effects. This was followed by an accelerating expansion of investigations of the nature of these radiobiological phenomena, the beginnings of studies aimed toward better understanding the underlying mechanisms, and a better appreciation of the far-reaching implications for biology, and for society in general. Areas of principal importance included acute tissue and tumor responses for applications in medicine, whole-body radiation effects in plants and animals, radiation genetics and cytogenetics, mutagenesis, carcinogenesis, cellular radiation responses including cell reproductive death, cell cycle effects and checkpoint responses, underlying molecular targets leading to biological effects, DNA repair, and the genetic control of radiosensitivity. This review summarizes some of the highlights in these areas, and points to numerous examples where indeed, many things of considerable fundamental importance have been learned by irradiating cells.

[The redox homeostasis system in radiation-induced genomic instability]. / Sistema okislitel'no-vosstanovitel'nogo gomeostaza pri radiatsionno-indutsiruemoi nestabil'nosti genoma.

The participation of the redox homeostasis system in the formation of the radiation-induced genome instability and new data of literature, that give a direct evidence the presence of this instability in vivo, is considered. The O2.-, H2O2 and NO. role as signal molecules, that triggered the cascade of active responses to change of redox status of the cells, are discussed. These compounds are mediators, that triggered the expression of specific genes. The reactive oxygen species (ROS) reorganize the membrane physico-chemical system of cell metabolism regulation. The composition, structure and function of cell membranes are changed, the membrane-bound proteins are modified. The data about changes in ROS generation system, including NO, that lead to genome instability after ionizing irradiation even in low doses, are analyzed. It is noted, that the radiation-induced genome instability and ROS production increase may be observed both in direct irradiated cells and their progeny and in the cells, that are not find oneself in ionization tracks, and their progeny. There are evidences that the genome instability of irradiated cell progeny is maintained by the increased ROS production. One of the mechanisms of genome instability transduction is carried out over "bystander effect", triggered by ROS.

[Induced germ line genomic instability at mini- and micro-satellites in animals]. / Indutsirovannaia nestabil'nost' genoma polovykh kletok zhivotnykh po mini- i mikrosatellitnym posledovatel'nostiam.

The recent data on the phenomenon of the induced germline genomic instability at mini- and microsatellites in animals were considered. Natural hypervariability of the minisatellites and microsatellites and their abundance in eukaryotic genome provide it's utility as the useful genetic markers for evaluation of the germline mutation frequency induced by treatment with different type of genotoxic factors at the low doses. High sensitivity of assays and possibility for direct determinations of the mutations, without the necessity to use extrapolation, are ensured. Some discussion is presented on the role of non-targeted mechanisms for the radiation-prone DNA lesions in the induction of germline genomic instability and also on the involving in this process the recombination events upon meiosis or during the early development stages of embryos. It is proposed that quantitative determination of germline genomic instability rate may be used as an acceptable variant for the genetic risk assessment and as indicator of increased probability for cancer and other pathologies at the offspring born to irradiated parents.

[Problems of the mechanism of radiation and chemical hormesis]. / Problemy mekhanizma radiatsionnogo i khimicheskogo gormezisa.

Based on the "membrane" mechanism of biological action of low radiation doses, described earlier, a possible common explanation of radiation and chemical hormesis initiation is proposed.

Gene-trap mutagenesis: past, present and beyond.

Although at least 35,000 human genes have been sequenced and mapped, adequate expression or functional information is available for only approximately 15% of them. Gene-trap mutagenesis is a technique that randomly generates loss-of-function mutations and reports the expression of many mouse genes. At present, several large-scale, gene-trap screens are being carried out with various new vectors, which aim to generate a public resource of mutagenized embryonic stem (ES) cells. This resource now includes more than 8,000 mutagenized ES-cell lines, which are freely available, making it an appropriate time to evaluate the recent advances in this area of genomic technology and the technical hurdles it has yet to overcome.

Mechanism of the fluorescent light induced suppression of Curly phenotype in Drosophila melanogaster.

A dominant mutation Curly (Cy), frequently used as a marker on the second chromosome in Drosophila melanogaster, was previously shown to be suppressed by several factors, including larval crowding, low temperature, and fluorescent light. While the first two factors affect this mutation only partially, fluorescent tube exposed flies exhibit an almost completely suppressed (wild type) phenotype. This suppressive effect is the result of a combination of the electric field and light, both factors being produced by common fluorescent tubes. In this study, experiments were carried out to clarify the basic mechanism of this unique phenomenon. Two fluorescent tube sensitive stages of Drosophila development were found in the second half of embryonic development and first half of the pupal stage. Riboflavin, which is administered to Drosophila larvae with yeast, and decomposed by light, seems to play a key role in this phenomenon. In a medium lacking riboflavin caused by light exposure, Cy expression is inhibited by the action of electric field. Positive results of experiments with lithium ions, which block the opening of Ca(2+) channels, support the hypothesis that electromagnetic fields may alter ion currents during ontogenic development of Drosophila, and thus influence, expression of the Cy gene. Also, fluorescent light induces an overexpression of a specific protein in the imaginal wing disc of Cy pupae.