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.     

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.     

Animal models for the study of the effects of spaceflight on the immune system.

Animal models have been used to determine the effects of spaceflight on the immune system. Rats and rhesus monkeys have been the primary animals used for actual space flight studies, but mice have also been utilized for studies in ground-based models. The primary ground based model used has been hindlimb unloading of rodents, which is similar to the chronic bed-rest model for humans. A variety of immune responses have been shown to be modified when animals are hindlimb unloaded. These results parallel those observed when animals are flown in space. In general, immune responses are depressed in animals maintained in the hindlimb unloading model or flown in space. These results raise the possibility that spaceflight could result in decreased resistance to infection in animals.     

Blood and clonogenic hemopoietic cells of newts after the space flight.

Ribbed newts were used for studying the effect of space flight on board of the biosatellite (Cosmos-2229) on blood and clonogenic hemopoietic cells. In blood of newts of the flight group, the relative proportion of neutrophils increased, whereas that of lymphocytes and eosinophils decreased. Space flight did not result in loss of the ability of newt blood cells to incorporate H3-thymidine. Analysis of clonogenic hemopoietic cells was performed using the method of hemopoietic colony formation on cellulose acetate membranes implanted into the peritoneal cavity of irradiated newts. To analyze reconstitution of hemopoiesis after irradiation donor hemopoietic cells from flight or control newts were transplanted into irradiated newts whose hemopoietic organs were investigated. The newt can be considered an adequate model for studying hemopoiesis under the conditions of the space flight.     

Induction of high grade astrocytoma (HGA) by protons: molecular mechanisms and RBE considerations.

Protons of a specific energy, 55 MeV, have been found to induce primary high grade astrocytomas (HGA) in the Rhesus monkey (Macaca mulatta). Brain tumors of this type were not induced by protons of other energies (32-2,300 MeV). Induction of HGA has been identified in human patients who have had radiation therapy to the head. We believe that the induction of HGA in the monkey is a consequence of dose distribution, not some unique "toxic" property of protons. Comparison of the human experience with the monkey data indicates the RBE for induction of brain tumors to be about one. It is unlikely that protons cause an unusual change in oncogenic expression, as compared to conventional electromagnetic radiation.     

State of erythrocyte membrane in man and monkeys after space flight.

The lipid and phospholipid composition of the erythrocyte membrane was investigated in man after long space flight and monkey after short space. The result obtained confirm structural changes in EM under the influence of SF factors and show that an increase of Ch and ChE fractions and in the Ch&ChE/PL ratio combined with a decrease of PL fractions. It was noticed that the magnitude of these changes is depend on duration of space flight.     

Accumulation of tumor suppressor p53 in rat muscle after a space flight.

Tumor suppressor p53 functions as a cell cycle checkpoint under stressful conditions. Early studies have shown that genotoxic stress activates p53 pathway. Recently, many kinds of non-genotoxic stress such as heat shock, cold shock, and low pH also have been found to activate p53 pathway. The effects on living organism remains to be explored. Here, we show that an 18-day space flight induced a 3.6 fold accumulation of p53 in rat skeletal muscle. This results suggests that the p53 pathway plays a role in safeguarding genomic stability against the stressful space environments and supports our previous observation of p53 accumulation in rat skin after a space flight.     

太空环境对肿瘤细胞生理特性的影响

将3种肿瘤细胞搭载于“神舟4号”的卫星返回舱内,经过7天太空飞行,回收后对存活细胞进行单克隆化,观察细胞形态,并测定了细胞周期、黏附力及细胞因子表达.结果显示,经太空飞行,小鼠黑色素瘤B16细胞的周期发生改变,G1期细胞明显增多(p<0.05),并表现多种细胞形态;人肺鳞癌细胞L78对血管内皮细胞黏附力明显减弱,但经传代培养其黏附力恢复且超过对照组细胞;Caski细胞IL-2、IL-8、TNF和TGF的表达均明显增加,而L78细胞上述4种细胞因子的表达均显著下降.结论,太空环境可影响肿瘤细胞的某些生理特性,但可否影响肿瘤细胞的免疫原性,仍需做进一步的实验.     

Production and action of cytokines in space.

B6MP102 cells, a continuously cultured murine bone marrow macrophage cell line, were tested for secretion of tumor necrosis factor-alpha and Interleukin-1 during space flight. We found that B6MP102 cells secreted more tumor necrosis factor-alpha and interleukin-1 when stimulated in space with lipopolysaccharide than controls similarly stimulated on earth. This compared to increased secretion of interferon-beta and -gamma by lymphocytes that was measured on the same shuttle flights. Although space flight enhanced B6MP102 secretion of tumor necrosis factor-alpha, an experiment on a subsequent space flight (STS-50) found that cellular cytotoxicity, mediated by tumor necrosis factor-alpha, was inhibited.     

Ultrastructural and growth indices of Chlorella culture in multicomponent aquatic systems under space flight conditions.

Submicroscopic organization of Chlorella cells cultivated under space flight conditions in three-component aquatic system has been studied. Comparison of the experimental cells with that of the controls revealed certain rearrangements of cell organelles particularly, a reduction in the amount of reserve polysaccharides in chloroplasts, increase of cell vacuolization and mitochondrion volume, complication configuration of plasmalemma evaginations and invaginations, and also disturbances in the process of cytokinesis. More over an increase in the number of Chlorella cells infected by bacteria was shown in the experimental variant. No considerable differences were established in the growth characteristics of the experimental and control populations. A comparative cytological analysis revealed general regularities of organelles in Chlorella cells cultivated under space flight condition in the uni- and multicomponent systems.     

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,为空间小鼠实验有效载荷设计提供地面对照;从实验研究内容和硬件系统设计两方面介绍了国际上已开展的空间小鼠实验,为中国空间生命科学研究和工程研制提供参考;对于中国发展空间小鼠实验有效载荷提出了建议.      

Prebiotic synthesis of nucleotides at the Earth orbit in presence of Lunar soil.

Modern studies now favor the fact that extraterrestrial organic molecules served as an important source of biological important substances on the primitive Earth. It is presumed that these space-made organic molecules could be transported safely to the Earth surface being associated with mineral grains. It is important to test whether nucleotides synthesized in Earth orbit could be protected by lunar surface regolite. The phosphorylation of adenosine, uridine and thymidine has been studied with respect of their further transformations and degradation in presence of mineral bed. After retrieval, HPLC analysis is used to identify all the mononucleotides of certain nucleosides. It has been shown, that exposure of the investigated nucleosides as dry films in space conditions in the presence of Lunar soil increases the yield of synthesized nucleotides in 1.1-3.0 times as compared with the exposure of the same samples in absence of Lunar soil. To identify and evaluate the principal source of energy in open space responsible for nucleotide synthesis reaction laboratory experiments were performed. It has been shown, that vacuum ultra violet (VUV 145 nm) radiation promotes nucleotide synthesis more effectively than ultra violet (UV 254 nm) while the presence of Lunar soil increases reaction yield in 1.5-2.0 times. Formation of 5'-mononucleotides seemed to be the most effective reaction both in flight and in laboratory experiments. Protective action of lunar soil on synthesized nucleotides against UV radiation has been shown in open Space conditions.     

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.     

Metabolic energy required for flight.

This paper reviews data available from U.S. and U.S.S.R. studies on energy metabolism in the microgravity of space flight. Energy utilization and energy availability in space seem to be similar to those on Earth. However, negative nitrogen balances in space in the presence of adequate energy and protein intakes and in-flight exercise, suggest that lean body mass decreases in space. Metabolic studies during simulated (bed rest) and actual microgravity have shown changes in blood glucose, fatty acids, and insulin levels, suggesting that energy metabolism may be altered during flight. Future research should focus on the interactions of lean body mass, diet, and exercise in space and their roles in energy metabolism during space flight.     

Some results of the effect of space flight factors on Drosophila melanogaster.

Two experiments with Drosophila melanogaster males were performed aboard the Salyut 6 orbital station. Mutagenic effects of a 8 day space flight on sex chromosome nondisjunction and intergene recombination in chromosome II were studied. The space flight factors (SFF) increased the frequency of chromosome nondisjunction and recombination. The model experiments showed that the combined effects of vibration and acceleration do not cover the whole spectrum of space flight mutagenic factors. These data suggest that heavy space ions are mainly responsible for the observed effect.     

Haemopoietic cell renewal in radiation fields.

Space flight activities are inevitably associated with a chronic exposure of astronauts to a complex mixture of ionising radiation. Although no acute radiation consequences are to be expected as a rule, the possibility of Solar Particle Events (SPE) associated with relatively high doses of radiation (1 or more Gray) cannot be excluded. It is the responsibility of physicians in charge of the health of astronauts to evaluate before, during and after space flight activities the functional status of haemopoietic cell renewal. Chronic low level exposure of dogs indicate that daily gamma-exposure doses below about 2 cGy are tolerated for several years as far as blood cell concentrations are concerned. However, the stem cell pool may be severely affected. The maintenance of sufficient blood cell counts is possible only through increased cell production to compensate for the radiation inflicted excess cell loss. This behaviour of haemopoietic cell renewal during chronic low level exposure can be simulated by bioengineering models of granulocytopoiesis. It is possible to define a "turbulence region" for cell loss rates, below which an prolonged adaptation to increased radiation fields can be expected to be tolerated. On the basis of these experimental results, it is recommended to develop new biological indicators to monitor haemopoietic cell renewal at the level of the stem cell pool using blood stem cells in addition to the determination of cytokine concentrations in the serum (and other novel approaches). To prepare for unexpected haemopoietic effects during prolonged space missions, research should be increased to modify the radiation sensitivity of haemopoietic stem cells (for instance by the application of certain regulatory molecules). In addition, a "blood stem cell bank" might be established for the autologous storage of stem cells and for use in space activities keeping them in a radiation protected container.     

Development of human epithelial cell systems for radiation risk assessment.

The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-LET radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic transformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.     

CSCW在空中交通管理中的应用

为了提高空中交通管理中航空器放行协作的工作效率,减少协作中的差错,利用计算机支持协作工作(CSCW,Computer Supported Cooperative Work)的理论和方法,设计实现了一种通用性强、适用性好的CSCW航空器放行协作系统.实际应用表明,该系统大大提高了航空器放行协作的工作效率,减轻了工作人员的工作负担,减少了错误的发生,具有很强的实用价值.