Cellular changes in microgravity and the design of space radiation experiments.

Cell metabolism, secretion and cell-cell interactions can be altered during space flight. Early radiobiology experiments have demonstrated synergistic effects of radiation and microgravity as indicated by increased mutagenesis, increased chromosome aberrations, inhibited development, and retarded growth. Microgravity-induced changes in immune cell functions include reduced blastogenesis and cell-mediated, delayed-type hypersensitivity responses, increased cytokine secretions, but inhibited cytotoxic effects and macrophage differentiation. These effects are important because of the high radiosensitivity of immune cells. It is difficult to compare ground studies with space radiation biology experiments because of the complexity of the space radiation environment, types of radiation damage and repair mechanisms. Altered intracellular functions and molecular mechanisms must be considered in the design and interpretation of space radiation experiments. Critical steps in radiocarcinogenesis could be affected. New cell systems and hardware are needed to determine the biological effectiveness of the low dose rate, isotropic, multispectral space radiation and the potential usefulness of radioprotectants during space flight.     

Biological dosimetry in Russian and Italian astronauts.

Large uncertainties are associated with estimates of equivalent dose and cancer risk for crews of long-term space missions. Biological dosimetry in astronauts is emerging as a useful technique to compare predictions based on quality factors and risk coefficients with actual measurements of biological damage in-flight. In the present study, chromosomal aberrations were analyzed in one Italian and eight Russian cosmonauts following missions of different duration on the MIR and the international space station (ISS). We used the technique of fluorescence in situ hybridization (FISH) to visualize translocations in chromosomes 1 and 2. In some cases, an increase in chromosome damage was observed after flight, but no correlation could be found between chromosome damage and flight history, in terms of number of flights at the time of sampling, duration in space and extra-vehicular activity. Blood samples from one of the cosmonauts were exposed in vitro to 6 MeV X-rays both before and after the flight. An enhancement in radiosensitivity induced by the spaceflight was observed.     

The role of weightlessness in the genetic damage from preflight gamma-irradiation of organisms in experiments aboard the Salyut 6 orbital station

The effect of weightlessness on chromosomal aberration frequency in preflight irradiated $\text{Crepis capillaris}$ seeds, on the viability, fertility and mutation frequency in $\text{Arabidopsis thaliana}$, and on the frequency of nondisjunction and loss of X chromosomes in preflight irradiated $\text{Drosophila melanogaster}$ gametes was studied aboard the Salyut 6 orbital station. The following effects were observed: a flight-time dependent amplification of the effects of preflight

-irradiation in $\text{A}$. $\text{thaliana}$ with respect to all the parameters studied; unequal effects in seeds and seedlings of $\text{Crepis capillaris}$; and a significant increase in the frequency of nondisjunction and loss of chromosomes during meiosis in $\text{Drosophila}$ females. These observations are discussed in terms of the data of ground-based model experiments and flight experiments with a different time of exposure of objects to weightlessness. An attempt is made to elucidate the role of weightlessness in the modification of ionizing radiation effects.     

Unique radiobiological aspects of high-LET radiation.

Since the beg inning of manned space flight the potentially unique radiobiological properties of the heavy ions of the cosmic radiation had been, apart from possible interactions of radiation effects with biological effects of weightlessness, of major concern with respect to the assessment of radiation hazards in manned space flight. Radiobiological findings obtained from space flight experiments and ground based experiments with densely ionizing radiation are discussed, which suggest qualitative differences between the radiobiological mechanisms of sparsely ionizing and densely ionizing radiation. These findings comprise the observation of a long lateral range of radiobiological effectiveness around tracks of single heavy ions, the observation of micro lesions induced in biological targets by the penetration of heavy ions, the nonadditivity of radiobiological effects from sparsely and densely ionizing radiation, the different kinetics for the expression of late effects induced by sparsely or densely ionizing radiation, and the observation of a reversed dose rate effect for early and late effects induced by densely ionizing radiation. These findings bear on the radiation protection standards to be installed for a general public in manned space flight and on the design of experiments, which intend to contribute to their specification.     

Space flight experiment on Chinese silkworm on board the Russian 10th Biosatellite.

Space flight experiments on Chinese silkworm (Bombyx mori L.) were conducted on board the Russian 10th Biosatellite for 12 days. The samples included silkworm eggs, larvae, cocoons, pupae and moths. The processes of spinning, cocooning, mating, oviposition, larval hatching, pupation and moth emergence all completed well in space. The following effects of space flight on silkworm development were observed: The times of hatching and oviposition in the flight group were 2 to 3 days earlier than in the control group; the hatching rate of diapause eggs during space flight seemed higher than that of the control group; the life span of 2 of the 7 varieties flown was shortened; genetical variations appeared in 3 varieties. The results showed that the embryonic stage was probably the period most sensitive to the space flight environment.     

Radiosensibility of higher plant seeds after space flight.

The influence of long-term storage of higher plant seeds under space flight conditions (49 to 827 days) on their radiosensibility was studied in the experiments on the orbital stations Salyut 6 and 7. Short-term storage has been proved to have no effect on radiosensitivity of Crepis capillaris seeds. Only in the case of maximal exposure duration the frequency of chromosome aberrations in post-flight irradiated seeds significantly exceeded the chromosome aberration frequency in the ground-based irradiated control. A statistically significant increase in the number of cells with multiple chromosome aberrations was also observed in this experiment. After gamma-irradiation of Arabidopsis thaliana seeds the germinating ability and survival rate of plants decreased depending on the duration of seed storage. Flight-exposed seeds were more sensitive to irradiations with respect to these parameters. A statistically significant increase in the frequency of recessive lethal mutations was observed only in two experiments of long exposure duration.     

空间小鼠实验有效载荷研究进展

啮齿动物是空间研究中常见的模型对象,已开展的空间生物实验中,小鼠表现出对飞行条件的有效适应.通过空间培养,研究者可对失重环境下小鼠的生理行为、骨骼和神经系统变化做进一步研究分析.本文对空间小鼠实验有效载荷的研究进展及其空间飞行实验进行了概述,为中国空间站上的小鼠培养箱设计提供参考.概述了地面小鼠培养技术和装置,为空间小...     

Large-size space laboratory for biological orbit experiments.

The study of space factors on living systems has great interest and long-term experiments during orbital flight will be important tool for increasing our knowledge. Realization of such experiments is limited by constraints of modern space stations. A new technology of large-size space laboratory for biological experiments has been developed on the basis of polymerization techniques. Using this technique there are no limits of form and size of laboratory for a space station that will permit long term experiments on Earth orbit with plants and animals in sufficient volume for creation of closed self-regulating ecological systems. The technology is based on experiments of the behavior of polymer materials in simulated free space conditions during the reaction of polymerization. The influences of space vacuum, sharp temperature changes and space plasma generated by galactic rays and Sun irradiation on chemical reaction were evaluated in their impact on liquid organic materials in laboratory conditions. The results of our study shows, that the chemical reaction is sensitive to such space factors. But we believe that the technology of polymerization could be used for the creation of space biological laboratories in Earth orbit in the near future.     

Space environmental factors affecting responses to radiation at the cellular level.

Previous space experiments suggest a high value for the RBE of cosmic radiation. A possible explanation could be a change in cell radiosensitivity due to a combined effect of radiation and other factors related to the space environment and to the space flight. Results of the EXOBLOC II experiment support this assumption. On earth, vibrations or accelerations applied before or after irradiation can change the responses to radiation. Microgravity could be the main factor affecting the radiosensitivity and DNA repair but this hypothesis must be confirmed by additional experiments.     

Effects of gravity perturbation on developing animal systems

Developing systems provide unique opportunities for analyzing the effects of microgravity on animals. Several unusual types of cells as well as various extraordinary cellular behavior patterns characterize the embryos of most animals. Those features have been exploited as test systems for space flight. The data from previous experiments are reviewed, and considerations for the design of future experiments are presented.     

Effects of space flight on surface marker expression.

Space flight has been shown to affect expression of several cell surface markers. These markers play important roles in regulation of immune responses, including CD4 and CD8. The studies have involved flight of experimental animals and humans followed by analysis of tissue samples (blood in humans, rats and monkeys, spleen, thymus, lymph nodes and bone marrow in rodents). The degree and direction of the changes induced by space flight have been determined by the conditions of the flight. Also, there may be compartmentalization of the response of surface markers to space flight, with differences in the response of cells isolated from blood and local immune tissue. The same type of compartmentalization was also observed with cell adhesion molecules (integrins). In this case, the expression of integrins from lymph node cells differed from that of splenocytes isolated from rats immediately after space flight. Cell culture studies have indicated that there may be an inhibition in conversion of a precursor cell line to cells exhibiting mature macrophage characteristics after space flight, however, these experiments were limited as a result of technical difficulties. In general, it is clear that space flight results in alterations of cell surface markers. The biological significance of these changes remains to be established.     

Achievements of Space Scientific Experiments Aboard SJ-8 Satellite

As scientific experiment payloads, microgravity experiments of fluid physics, life science,combustion science, physics and accelerator measurement were conducted on board the Chinese recoverable satellite SJ-8 during 18-day orbital flight. The experimental payloads and an experiment support system constituted the microgravity experiment system of the flight mission. This article has presented the briefs of the scientific achievements of these space experiments, the composition and performance of the Microgravity Experimental System (MES) and the general picture of the overall flight mission, respectively.      

Space flight, microgravity, stress, and immune responses.

Exposure of animals and humans to space flight conditions has resulted in numerous alterations in immunological parameters. Decreases in lymphocyte blastogenesis, cytokine production, and natural killer cell activity have all been reported after space flight. Alterations in leukocyte subset distribution have also been reported after flight of humans and animals in space. The relative contribution of microgravity conditions and stress to the observed results has not been established. Antiorthostatic, hypokinetic, hypodynamic, suspension of rodents and chronic head-down tilt bed-rest of humans have been used to model effects of microgravity on immune responses. After use of these models, some effects of space flight on immune responses, such as decreases in cytokine function, were observed, but others, such as alterations in leukocyte subset distribution, were not observed. These results suggest that stresses that occur during space flight could combine with microgravity conditions in inducing the changes seen in immune responses after space flight. The biological/biomedical significance of space flight induced changes in immune parameters remains to be established. Grant Numbers: NCC2-859, NAG2-933.     

Selection and biomedical training of cosmonauts.

The first cosmonauts were selected from the flying personnel. These individuals enjoying good health were more familiar with the conditions and effects of the factors similar to those which are to be found in space missions. In future, because of the complication of tasks to be solved in space missions, an inflight utilization and testing of sophisticated space technology, and conducting a broad spectrum of scientific studies, a demand arose for including cosmonaut-researchers--highly qualified representatives of various scientific specialities--in a flight crew. In this connection, a necessity was created for changing some evaluation criteria to assess the health status of the chosen candidates considering their age and physical fitness. In specific cases, during the selection process some health-improving measures related to professional significance of the candidates for a position of cosmonaut-researcher was carried out. The prime goal of cosmonauts selection is to predict their good tolerance for a particular space mission while maintaining health and adequate performance throughout the flight, completing the flight tasks and assuring successful return to the Earth. Inclusion of cosmonaut-researchers in space crews requires study of an effect of spaceflight factors on reactions of female subjects in simulated ground-based investigations. At present, the preparation of cosmonauts, can be defined as a continuous purposeful process of training, forming and maintaining operational skills, bringing up the crewmembers to acquire professionally significant psychological and physical features essential for effective work to be done in space mission. The preparation of cosmonauts consists mainly of technical, aviation and space, medical-biological and scientific trainings.     

Neurobiological problems in long-term deep space flights.

Future missions in space may involve long-term travel beyond the magnetic field of the Earth, subjecting astronauts to radiation hazards posed by solar flares and galactic cosmic rays, altered gravitation fields and physiological stress. Thus, it is critical to determine if there will be any reversible or irreversible, detrimental neurological effects from this prolonged exposure to space. A question of particular importance focuses on the long-term effects of the space environment on the central nervous system (CNS) neuroplasticity, with the potential acute and/or delayed effects that such perturbations might entail. Although the short-term effects of microgravity on neural control were studied on previous low earth orbit missions, the late consequences of stress in space, microgravity and space radiation have not been addressed sufficiently at the molecular, cellular and tissue levels. The possibility that space flight factors can interact influencing the neuroplastic response in the CNS looms critical issue not only to understand the ontogeny of the CNS and its functional integrity, but also, ultimately the performance of astronauts in extended space forays. The purpose of this paper is to review the neurobiological modifications that occur in the CNS exposed to the space environment, and its potential consequences for extended deep space flight.     

Estimation of a cosmonaut's radiation hazard during long-term space missions on the basis of a generalized dosimetric function.

This paper presents a new concept of radiation hazard assessment for spacecraft crew members during long term space missions on the basis of a generalized dosimetric function. This new dosimetric function enables a complicated nature of space radiation exposure to be reduced to the conditions of a standard irradiation. It can be obtained on the basis of mean-tissue equivalent dose values calculated for each space radiation source and transmission coefficients describing the influence of the complex spatial and temporal distribution of the absorbed dose in the cosmonaut's body on the radiobiological effects. The combination of cosmic ionizing radiation with other non-radiation nature factors in flight can also be accounted for. In terms of the generalized dose, it is possible to assess the nature and extent of lowering a crew working capacity, as well as radiation risk, both during a flight and post flight period.     

Changes in the central nervous system during long-duration space flight: implications for neuro-imaging.

The purpose of this paper is to review the potential functional and morphological effects of long duration space flight on the human central nervous system (CNS) and how current neuroimaging techniques may be utilized to study these effects. It must be determined if there will be any detrimental changes to the CNS from long term exposure to the space environment if human beings are to plan interplanetary missions or establish permanent space habitats. Research to date has focused primarily on the short term changes in the CNS as the result of space flight. The space environment has many factors such as weightlessness, electromagnetic fields, and radiation, that may impact upon the function and structure of the CNS. CNS changes known to occur during and after long term space flight include neurovestibular disturbances, cephalic fluid shifts, alterations in sensory perception, changes in proprioception, psychological disturbances, and cognitive changes. Animal studies have shown altered plasticity of the neural cytoarchitecture, decreased neuronal metabolism in the hypothalamus, and changes in neurotransmitter concentrations. Recent progress in the ability to study brain morphology, cerebral metabolism, and neurochemistry in vivo in the human brain would provide ample opportunity to investigate many of the changes that occur in the CNS as a result of space flight. These methods include positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI).     

The influence of space flight factors on viability and mutability of plants.

The experiments with air-dried Crepis capillaris seeds aboard the Soyuz 16 spaceship and the orbital stations Salyut 5, 6, 7 have revealed an increase in the frequency of aberrant cells in seedlings grown from flight-exposed seeds during the flight (experiment) and after the flight on Earth (flight control) as compared to the ground-based control. The increase in seedlings grown during the flight is more significant than in the flight control. During the flight Arabidopsis thaliana developed from cotyledons to the flowering stage. Analysis of seeds setting on these plants after the flight has shown a reduction in the fertility of these plants and an increase in the frequency of recessive mutants ("Light block-1"). An increased frequency of mutants was also retained in the progeny of plants which had passed through a complete cycle of development during the flight ("Fiton-3"). Suppression of embryo viability was observed in all experiments and expressed itself in reduced germinating ability of seeds from the exposed plants and in the early death of seedlings. Damages resulting from chromosome aberrations are eliminated in the first postflight generation and damages resulting from gene mutations and micro-aberrations are preserved for a longer time.     

The gravitational field and brain function.

The frontal cortex is recognized as the highest adaptive control center of the human brain. The principle of the "frontalization" of human brain function offers new possibilities for brain research in space. There is evolutionary and experimental evidence indicating the validity of the principle, including it's role in nervous response to gravitational stimulation. The gravitational field is considered here as one of the more constant and comprehensive factors acting on brain evolution, which has undergone some successive crucial steps: "encephalization", "corticalization", "lateralization" and "frontalization". The dominating effects of electrical responses from the frontal cortex have been discovered 1) in experiments under gravitational stimulus; and 2) in processes potentially relating to gravitational adaptation, such as memory and learning, sensory information processing, motor programing, and brain state control. A brain research experiment during space flight is suggested to test the role of the frontal cortex in space adaptation and it's potentiality in brain control.     

Effects of space flight and IGF-1 on immune function

We tested the hypothesis that insulin-like growth factor-1 (IGF-1) would ameliorate space flight-induced effects on the immune system. Twelve male, Sprague-Dawley rats, surgically implanted with mini osmotic pumps, were subjected to space flight for 10 days on STS-77. Six rats received 10 mg/kg/day of IGF-1 and 6 rats received saline. Flight animals had a lymphocytopenia and granulocytosis which were reversed by IGF-1. Flight animals had significantly higher corticosterone levels than ground controls but IGF-1 did not impact this stress hormone. Therefore, the reversed granulocytosis did not correlate with serum corticosterone. Space flight and IGF-1 also combined to induce a monocytopenia that was not evident in ground control animals treated with IGF-1 or in animals subjected to space flight but given physiological saline. There was a significant increase in spleen weights in vivarium animals treated with IGF-1, however, this change did not occur in flight animals. We observed reduced agonist-induced lymph node cell proliferation by cells from flight animals compared to ground controls. The reduced proliferation was not augmented by IGF-1 treatment. There was enhanced secretion of TNF, IL-6 and NO by flight-animal peritoneal macrophages compared to vivarium controls, however, O₂ secretion was not affected. These data suggest that IGF-1 can ameliorate some of the effects of space flight but that space flight can also impact the normal response to IGF-1.