One major concern regarding long-term manned space missions is the effect of accumulative doses of space radiation (the mean daily dose is 0.2 ∼ 1 mSv). Such missions will inevitably expose astronauts to significant doses, and thus are expected to increase the risks of radiation-related carcinogenicity, neurotoxicity, and lifespan changes. These effects occur by nuclear and cytosol dysfunction, mitochondrial damage, and particular changes in signal transduction or protein synthesis. In addition, microgravity may affect cellular metabolisms, signal transduction, etc., and might lead to synergistic effects with space radiation, which could result in further risk. Because these effects will almost certainly involve cellular signaling, transcriptomics and proteomics will be powerful tools in their analysis. In order to suitably respond to all these risks, both protective measures based on physical and biological principles, and effective intra-flight assessment of the levels of radiation exposure will be required. In this article, the categories of cell death-i.e., apoptosis, necrosis and autophagy-and the recent studies on these mechanisms are reviewed.

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We investigated the influence of mutation induction on the hypoxanthine guanine phosphoribosyltransferase (hprt) locus in normal human fibroblasts irradiated with X rays or accelerated iron ions with LET ranging from 200 to 400 keV/μm. The relative biological effectiveness (RBE) of the mutation frequency per total number of surviving cells for iron ions with comparatively lower LET values (200 and 260 keV/μm) in this study was higher than 1, and the RBE for the 300 keV/μm, 350 keV/μm and 400 keV/μm ions was nearly 1. These results indicated that the mutation induction for iron ions decreased with increasing LET, and these of high-LET regions (over 300 keV/μm) and X rays were similar. The deletion spectrum of exons in hprt locus for X rays and 260 keV/μm-iron ions were analyzed using multiplex polymerase chain reaction (PCR). About 70% of mutant induced by iron ions showed deletion of the entire exons (total deletion), while mutant induced by X rays showed partial deletion, which one or more exons are missing, of about 70%. The results indicated that iron-ion induced mutants sustained severer damage than X-ray induced mutants even if the dose-response curves for mutation induction were similar between X rays and iron ions.

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The authors have a plan to examine the biological effects of cosmic rays by loading the eggs of the silkworm, Bombyx mori, in the International Space Station (ISS) for 3 months. In advance of the project, several ground experiments have been performed. In order to investigate the biological effects of radiation, heavy ion particles were used instead of cosmic rays. Heterozygous eggs of the black-striped strain (p^S/p) were irradiated with Carbon (C), Neon (Ne) or Ferrous (Fe) ion particles. At the fifth instar stage, larvae that hatched from these eggs showed white spots on their backs against the black or dark brown of their integument. These are somatic mutations which seem to be caused by the effects of radiation on the p^S gene. The incidence of this somatic mutation increased in proportion to dose and linear energy transfer of C and Ne ion particles, and it was higher after resumption of embryogenesis in eggs that had been irradiated after diapause termination as compared with eggs irradiated while still in diapause. Irradiation by more than 0.04 Gy of Fe ion particles to diapause-terminated eggs induced a significant incidence of somatic mutation compared with controls (P<0.05). Furthermore, radiation effects were also detected at the next generation as detected by egg color mutations by using the specific locus method. In experiments investigating the effects of microgravity on silkworm embryogenesis in the US Space Shuttle/Atlantis (STS-84) in 1997, we had observed that microgravity could influence embryonic reversal, presumably resulting in abnormal development of embryos. On the basis of the results from STS-84 flight and the above mentioned ground experiments, the authors will examine the interrelationship between the dose of cosmic rays and the incidence of somatic mutation, as well as confirm and extend the analysis of synergistic effects between cosmic rays and microgravity on mutation rates in experiments conducted using the ISS. These data will provide fundamental information on the effects of cosmic rays on biological systems that can then be applied to better protect humans against cosmic radiation during space flight.

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Seedlings of Arabidopsis α-tubulin 6 mutant (tua6) were cultivated under microgravity conditions in the European Modular Cultivation System on the International Space Station, and growth and cell wall properties of their hypocotyls were analyzed (the Resist Wall experiment). Seeds of tua6 mutant were shown to germinate and grow normally until the seedling stage under microgravity conditions, as at 1 G on the ground. The seedlings were naturally air-dried in orbit, which were then recovered and transported to earth. When the mechanical properties of the cell wall of rehydrated hypocotyls were examined with a tensile tester, the hypocotyls showed typical stress-strain and stress-relaxation curves, as normally fixed or frozen materials. Also, no prominent differences were detected in the extensibility or the stress-relaxation parameters of the cell wall between space-grown hypocotyls and ground controls, suggesting that tua6 hypocotyls formed the regular cell wall architecture under microgravity conditions. The results and lessons learned from the Resist Wall experiment are expected to provide the basis for the following space experiments to clarify the mechanism of gravity resistance in plants.

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Physical activity is known to enhance the mechanical competence of weight-bearing bones, and it is also effective for the prevention of osteoporosis. However, little information is available regarding the optimum exercise and intensity of load to weight-bearing bones as well as about a precise system to monitor the intensity of physical activity. To measure the precise load to weight-bearing bones of exercise as a first step, this study is to evaluate the sampling conditions of data acquisition and develop an accelerometer-based physical activity monitoring and its intensity analysis system. Through a simulation experiment, we found that 1k Hz of sampling rate is possible to achieve a measurement error of less than 2%. With the optimum sampling rate of 1k Hz, we developed an accelerometer-based activity-monitoring system. We then assessed the magnitude of acceleration at the shank, knee, and lumber in healthy subjects (n=19) as they descended stairs. A correlation analysis of the precise acceleration values in three points of the body showed that our system could accurately identify the shock absorptive function of lower extremities. Therefore, we strongly believe that our system, with the optimum sampling rate of 1k Hz, produced an accurate measurement of loads acting on weight-bearing bones.

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The purpose of this study is to evaluate several kinds of stress factors for small animals used with ground-based experiment facilities such as drop towers, parabolic flights, or centrifuges; and to mitigate the stressors, with the exception of gravity, in order to increase the scientific value of the experiment data and improve animal conditions. In the first step, we conducted experiments in a drop tower (Micro-Gravity Laboratory of Japan; MGLAB, Toki-city) and examined the following factors. 1) Environmental factors: Monitored and controlled environmental factors, such as temperature, humidity, oxygen and carbon dioxide concentration. 2) Evaluation of stress on animals: Biochemistry, in situ hybridization histochemistry, behavior, and physiology. From these results, we are able to estimate the degree of stress in drop-tower experiments to be level two on a scale of one to five level from the mildest state. The data and know-how we acquired will be summarized as a handbook and published for animal experiments employing the drop tower.

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