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.     

On the radiosensitivity of man in space.

Astronauts' radiation exposure limits are based on experimental and epidemiological data obtained on Earth. It is assumed that radiation sensitivity remains the same in the extraterrestrial space. However, human radiosensitivity is dependent upon the response of the hematopoietic tissue to the radiation insult. It is well known that the immune system is affected by microgravity. We have developed a mathematical model of radiation-induced myelopoiesis which includes the effect of microgravity on bone marrow kinetics. It is assumed that cellular radiosensitivity is not modified by the space environment, but repopulation rates of stem and stromal cells are reduced as a function of time in weightlessness. A realistic model of the space radiation environment, including the HZE component, is used to simulate the radiation damage. A dedicated computer code was written and applied to solar particle events and to the mission to Mars. The results suggest that altered myelopoiesis and lymphopoiesis in microgravity might increase human radiosensitivity in space.     

Genetic susceptibility to radiation.

In the context of space radiation, it is important to know whether the human population includes genetically predisposed radiosensitive subsets. One possibility is that haploinsufficiency for ATM confers radiosensitivity, and this defect involves 1-3% of the population. Using knock-out mice we chose to study cataractogenesis in the lens and oncogenic transformation in mouse embryo fibroblasts to assay for effects of ATM deficiency. Radiation induced cataracts appeared earlier in the heterozygous versus wild-type animals following exposure to either gamma rays or 1 GeV/nucleon iron ions. In addition, it was found that embryo fibroblasts of Atm heterozygotes showed an increased incidence of oncogenic transformation compared with their normal litter-matched counterparts. From these data we suggest that Ataxia Telangiectasia heterozygotes could indeed represent a societally significant radio sensitive subpopulation. Knock-out mice are now available for other genes including BRCA1 and 2, and Mrad9. An exciting possibility is the creation of double heterozygotes for pairs of mutated genes that function in the same signal transduction pathway, and consequently confer even greater radiosensitivity.     

Deoxyribonucleoprotein structure and radiation injury: cellular radiosensitivity is determined by LET infinity -dependent DNA damage in hydrated deoxyribonucleoproteins and the extent of its repair.

For decades, theories of cellular radiosensitivity relied upon the initial patterns of energy deposition to explain radiation lethality. Such theories are unsound: cellular (DNA) repair also underlies cellular radiosensitivity. For the charged particles encountered in deep space, both the types of DNA damage caused in cellular deoxyribonucleoproteins and the efficacies of their repair are dependent on linear energy transfer (LET infinity), and repair efficiency is also influenced by cell and tissue type, i.e., the actual recovery processes involved. Therefore, quality factors derived from radiation quality alone are inadequate parameters for assessing the radiation risks of space flight. Until recently, OH radicals formed in bulk nuclear water were believed to be the major causes of DNA damage that results in cell death, especially for sparsely ionizing radiations. That hypothesis has now been challenged, if not refuted. Lethal genomic DNA damage is determined mainly by energy deposition in deoxyribonucleoproteins, and their hydration shells, and charge (energy) transfer processes within those structures.     

Space radiobiology program in Russia.

The space radiobiology program in Russia is aimed at obtaining fundamental data for developing radiation safety criteria. These criteria are necessary for long-term space missions. This program includes : -substantiation of radiation hazard estimation principles based on the radiation risk conception, -investigation of the radiation affection regularities under the combined influence of the spaceflight factors, -experimental investigation of the HZE-particle delayed effects and acute somatic effects induced by protons and electrons, -individual radiosensitivity investigation, -mathematic modeling of radiobiological effects , -radiobiological basis of control and forecast of radiation influence in space, -development of methods and means of an organism's radioresistance increase.     

Effects of long duration space flight on rice seed (or embryo) radiation sensitivity and element microlocalizations.

In long duration space experiments Rice caryopses and embryos, which are able to remain alive 10 years (or more) and tolerate extreme physical conditions (temperature, few water content) during irradiation and post-irradiation storage, were used (8, 40, 201 and 457 days on board of Salyut 7, 2107 days on LDEF). In certain experiments (Salyut 7), samples were irradiated either before or after the flight. Effects of the flight and radiosensitivity were observed in Rice seedlings cultivated in in vitro conditions. Statistical results indicate an increase in radiosensitivity when irradiations occur before the flight. Microanalyses were made in different parts of one caryopsis and of one embryo, and the results compared with those of control samples. With caryopses and embryos of the same Rice varieties, but from LDEF, we made the same kinds of experiments to compare results.     

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.     

Insects as test systems for assessing the potential role of microgravity in biological development and evolution.

Gravity and radiation are undoubtedly the two major environmental factors altered in space. Gravity is a weak force, which creates a permanent potential field acting on the mass of biological systems and their cellular components, strongly reduced in space flights. Developmental systems, particularly at very early stages, provide the larger cellular compartments known, where the effects of alterations in the size of the gravity vector on living organisms can be more effectively tested. The insects, one of the more highly evolved classes of animals in which early development occurs in a syncytial embryo, are systems particularly well suited to test these effects and the specific developmental mechanisms affected. Furthermore, they share some basic features such as small size, short life cycles, relatively high radio-resistance, etc. and show a diversity of developmental strategies and tempos advantageous in experiments of this type in space. Drosophila melanogaster, the current biological paradigm to study development, with so much genetic and evolutionary background available, is clearly the reference organism for these studies. The current evidence on the effects of the physical parameters altered in space flights on insect development indicate a surprising correlation between effects seen on the fast developing and relatively small Drosophila embryo and the more slowly developing and large Carausius morosus system. In relation to the issue of the importance of developmental and environmental constraints in biological evolution, still the missing link in current evolutionary thinking, insects and space facilities for long-term experiments could provide useful experimental settings where to critically assess how development and evolution may be interconnected. Finally, it has to be pointed out that since there are experimental data indicating a possible synergism between microgravity and space radiation, possible effects of space radiation should be taken into account in the planning and evaluation of experiments designed to test the potential role of microgravity on biological developmental and evolution.     

Survival of microorganisms in space protected by meteorite material: results of the experiment 'EXOBIOLOGIE' of the PERSEUS mission.

During the early evolution of life on Earth, before the formation of a protective ozone layer in the atmosphere, high intensities of solar UV radiation of short wavelengths could reach the surface of the Earth. Today the full spectrum of solar UV radiation is only experienced in space, where other important space parameters influence survival and genetic stability additionally, like vacuum, cosmic radiation, temperature extremes, microgravity. To reach a better understanding of the processes leading to the origin, evolution and distribution of life we have performed space experiments with microorganisms. The ability of resistant life forms like bacterial spores to survive high doses of extraterrestrial solar UV alone or in combination with other space parameters, e.g. vacuum, was investigated. Extraterrestrial solar UV was found to have a thousand times higher biological effectiveness than UV radiation filtered by stratospheric ozone concentrations found today on Earth. The protective effects of anorganic substances like artificial or real meteorites were determined on the MIR station. In the experiment EXOBIOLOGIE of the French PERSEUS mission (1999) it was found that very thin layers of anorganic material did not protect spores against the deleterious effects of energy-rich UV radiation in space to the expected amount, but that layers of UV radiation inactivated spores serve as a UV-shield by themselves, so that a hypothetical interplanetary transfer of life by the transport of microorganisms inside rocks through the solar system cannot be excluded, but requires the shielding of a substantial mass of anorganic substances.     

Mechanisms underlying cellular radiosensitivity and R.B.E.: introductory remarks.

A general outline of the symposium titled "Mechanisms underlying cellular radiosensitivity and R.B.E." will be given in the introduction. The essential topics of molecular radiation biology are described with respect to the damage, repair and mutagenesis caused by high-LET irradiation to cellular DNA. The importance of clustered DNA lesions (locally multiply damaged sites) formed in vivo is discussed. This symposium is devoted to the mechanisms of the biological effects of radiation with high LET, especially with regard to the effects of heavy ions and neutrons which may cause possible risks in space flight, (e.g. carcinogenesis and mutagenesis). Detailed understanding of these risks, however, demands knowledge of the molecular mechanisms involved in the biological effects of high-LET radiations. Thus, it was the organizers' idea to hold a symposium dealing with primary physical and chemical events caused in cellular deoxyribonucleoproteins by densely-ionizing radiations and to relate them to track structures and energy transfer processes. The mechanisms of DNA damage were regarded from different points of view including those considering DNA repair and mutagenesis. Problems associated with cell survival and radiation protection were discussed as well. Our knowledge of the molecular mechanisms of high-LET radiation actions, however, is limited compared to what we know about low-LET radiation effects (e.g. from gamma-rays or X-rays). To emphasize this statement, I would like to summarize briefly the open questions in molecular radiation biology, what we know already about low-LET effects and what is lacking describing the effect of high-LET radiation.     

Radiation biology in space: a critical review.

A short summary of the results of radiobiological studies in space or on respective particles on ground will be given. Among the various types of radiation in space, the effect of heavy ions with high energy (HZE-particles) are most essential. Thus, radiobiology in space concerns mostly to the effect of these particles, in cells and in whole organism. Cell death, mutation and malignant transformation are the relevant endpoints, with can be studied on ground with heavy ions of different energy with suitable accelerators or in space, especially by the BIOSTACK concept. In space, however, the effect of microgravity has to be considered as well and there are hints, that under weightlessness the biological effect of radiation may be enhanced. There are still open questions to be answered concerning radioprotection of man in space. Further experiments are necessary.     

Modifying factors on repair phenomena.

Every step of radiation damage repair can be modified by several factors like temporal and local energy distribution (LET), physiological conditions, biochemical and chemical composition of the target environment. Most interesting in the case of space radiation is the possible influence of high LET and of microgravity which could change the repair i.e. fusion capacity as well as the phenomenon of self assembly.     

Ground-based research with heavy ions for space radiation protection.

Human exposure to ionizing radiation is one of the acknowledged potential showstoppers for long duration manned interplanetary missions. Human exploratory missions cannot be safely performed without a substantial reduction of the uncertainties associated with different space radiation health risks, and the development of effective countermeasures. Most of our knowledge of the biological effects of heavy charged particles comes from accelerator-based experiments. During the 35th COSPAR meeting, recent ground-based experiments with high-energy iron ions were discussed, and these results are briefly summarised in this paper. High quality accelerator-based research with heavy ions will continue to be the main source of knowledge of space radiation health effects and will lead to reductions of the uncertainties in predictions of human health risks. Efforts in materials science, nutrition and pharmaceutical sciences and their rigorous evaluation with biological model systems in ground-based accelerator experiments will lead to the development of safe and effective countermeasures to permit human exploration of the Solar System.     

高稳晶振在空间辐照条件下的频率特性变化

在空间恶劣环境下要求星载高稳晶振正常有效地工作,需要对其在空间辐照环境下的频率特性变化进行研究,利用地面辐照设备模拟空间辐照环境,通过不断增加辐照剂量,研究晶振相位噪声、短期频率稳定度、谐杂波以及输出功率等特性。     

Genetic and physiological damage induced by cosmic radiation on dry plant seeds during space flight

Total evaluation of cosmic radiation effect with or without discrimination of individualized HZE-ion effects in dry seeds flown for 10 days on STS-9, yielded significant evidence for radiation damage in space. They depend on the biological criteria tested (seed germination, morphogenesis, embryo lethality, mutation rate) which stand for early, physiological and late genetic effects. They are also related to the radiation shielding environment in the space shuttle. Proceeding from these results three direct questions can be posed for present (LDEF-1) and future (ERA-1, D-2) experiments in space: What is the influence of cosmic radiation on cytogenetic repair and ontogenetic restitution processes? Does microgravity disorder the morphogenesis (i.e. growth and cell differentiation)? Is there an interaction between the effects of cosmic radiation and microgravity in eukaryotic plant systems?     

Inactivation of individual Bacillus subtilis spores in dependence on their distance to single cosmic heavy ions.

For radiobiological experiments in space, designed to investigate biological effects of the heavy ions of the cosmic radiation field, a mandatory requirement is the possibility to spatially correlate the observed biological response of individual test organisms to the passage of single heavy ions. Among several undertakings towards this goal, the BIOSTACK experiments in the Apollo missions achieved the highest precision and therefore the most detailed information on this question. Spores of Bacillus subtilis as a highly radiation resistant and microscopically small test organism yielded these quantitative results. This paper will focus on experimental and procedural details, which must be included for an interpretation and a discussion of these findings in comparison to control experiments with accelerated heavy ions.     

SJ-10 Recoverable Satellite for Space Microgravity Experiments

SJ-10 is a recoverable scientific experiment satellite specially for the space experiments of microgravity physics science and space life science. This mission was officially started on 31 December 2012, and the satellite was launched on 6 April 2016. This paper introduces briefly the SJ-10 mission, the progress of SJ-10 engineering and the project constitution of sciences experiments onboard SJ-10. The purpose of this mission is to discover the law of matter movement and the rule of life activity that cannot be discovered on the ground due to the existence of gravity, and to know the acting mechanism on organisms by the complex radiation of space that cannot be simulated on the ground.      

Possible mechanism of microgravity impact on Carausius morosus ontogenesis.

Experiments aboard "Spacelab-D1" and "Cosmos-1887" revealed an adverse effect of space flight on Carausius morosus embryos. The main influencing factor for stick insect eggs turned out to be microgravity, while the contribution of HZE particles of cosmic radiation was relatively low. Flight experiments indicated an increased vulnerability of stick insect eggs to microgravity at intermediate stages of development, that could support the "convection" hypothesis.     

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.     

光纤陀螺中保偏光纤60 Co辐照效应及光褪色特性

从光纤陀螺空间应用的角度出发,利用60Co辐照源模拟空间辐照,对光纤陀螺中的主要部件保偏光纤环进行了不同剂量率的辐照实验,得到了保偏光纤的辐照效应.并且利用大功率半导体激光器对保偏光纤环进行了光褪色实验.实验证明,辐照条件下,保偏光纤损耗增加;剂量率越大,损耗增加越快;总剂量越大,损耗越大;采用大功率半导体激光器对保偏光纤环进行光褪色,可以减缓辐照环境下光纤的损耗增加量,而且激光器功率越大,光褪色效果越明显,可将其用到光纤陀螺中作为其空间应用的抗辐射加固措施.