Influence of cosmic radiation and/or microgravity on development of Carausius morosus.

Eggs of Carausius morosus were exposed to spaceflight conditions in two spaceflight missions, the German 7 day Spacelab Mission D1 and the Soviet 12.56 day Biosatellite Mission "COSMOS 1887". During spaceflight the eggs continued their development. Eggs of five different ages representing different sensitivity to radiation and different capacity to regeneration were used to investigate the influence of cosmic radiation and/or microgravity on insect development. Using the Biostack concept--eggs in monolayers sandwiched between nuclear track detectors--and the 1 g reference centrifuge of BIORACK in D1 we were able to separate effects of heavy ions of the cosmic radiation from microgravity effects and also from combined effects of these two factors in space. After retrieval, hatching rates, embryonic and larval growth kinetics and anomaly frequencies were determined. Microgravity leads to a reduced hatching rate of eggs exposed in the early stages of development. Hatching was normal in eggs which were exposed on the 1 g reference centrifuge. Hits by heavy ions caused body anomalies. The combined action of heavy ions and microgravity resulted in an unexpectedly high frequency of anomalies. These results obtained from the Spacelab Mission D1, were confirmed in an experiment onboard of COSMOS 1887. In addition to the previous analysis, embryonic development before hatching was followed which showed no major difference between flight and the ground control specimens. Since a reconfirmation of reduced hatching rates was observed in COSMOS 1887, too, the above results suggest some microgravity induced functional impairment of the hatching activity, rather than blockage in embryonic development.     

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.     

A review and comparative analysis of the biological damage induced during space flight by HZE particles and space hadrons

We have studied the somatic and genetic effects of heavy ions (HZE particles) and the very high energy hadrons of space radiation on various organisms ranging in complexity from bacteriophage to man. Experimental data were obtained in space, on high mountains and in a proton accelerator at energies of 76 GeV. In all these experiments local micro- and macroradiational damage was observed. This damage was characterized by severity over large local regions and for the most part was due to cascades of secondary particle bundles resulting from the collosion of very high energy space hadrons with atomic nuclei rather than from cellular hits from relatively low energy single HZE particles. At present there does not appear to be any effective way to provide shielding against these cosmic hadrons.     

Results on Artemia cysts, lettuce and tobacco seeds in the Biobloc 4 experiment flown aboard the Soviet Biosatellite Cosmos 1129.

Artemia cysts, lettuce and tobacco seeds were flown aboard the Cosmos 1129 for 19 days. A correlative method was used in order to determine the passage of cosmic heavy ions (HZE particles) through the biological test objects. This space flight resulted in a decrease on hatchability, nucleic acid and protein synthesis in hydrated Artemia cysts. HZE particle effects on plant cellular chromosomes are confirmed. In tobacco seeds, a stimulating effect on germination rate and a higher frequency of abnormalities were observed. Dormant biological objects are a very suitable material to study cosmic ray effects: these objects can be arranged in monolayers and sandwiched between visual track detectors in order to determine the passage of the cosmic heavy ions (HZE particles). On the other hand this method allows us to study effects of microgravity and those of the protonic component of cosmic rays in the objects not hit by the HZE articles.     

The effects of proton exposure on neurochemistry and behavior.

Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints.     

Countermeasures for space radiation induced adverse biologic effects

Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.     

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.     

Microlesions: theory and reality.

Efforts to assess radiation risk in space have been complicated by the considerable unknowns regarding the biological effects of the heavy ion component (HZE particles) of the cosmic rays. The attention has focused primarily on the assignation of a quality factor (Q) which would take into account the greater effectiveness of heavy ions vis-a-vis other forms of ionizing radiation. If however, as the so-called "Microlesion Theory" allows, the passage of HZE particles through living tissue produces unique biological damage, the traditional use of Q becomes meaningless. Therefore, it is critical to determine if microlesions, in fact, do exist. While the concept does not necessarily require detectable morphological damage, "tunnel-lesions" or holes in ocular tissues have been cited as evidence of microlesions. These data, however, are open to reinterpretation. On-going light, scanning and transmission electron microscopic studies of the corneas, lenses and retinas of rat eyes exposed to 450 MeV/amu 56Fe ions thus far have not revealed tunnel-lesion damage. The morphological effects of the heavy ions have been found to be qualitatively similar to the changes following other kinds of ionizing radiation.     

Cosmic ionizing radiation effects in plant seeds after short and long duration exposure flights.

Recently, comparison of biophysical data obtained from orbital flights of short and long duration led to results which will be significant for long and/or repeated stay of man in space. Under orbital conditions biological stress is induced in dry seeds of Arabidopsis thaliana by cosmic radiation especially its high energetic, densely ionizing component, the heavy ions (HZE). For comparison of radiation impact during different space flights a biological attempt at estimating the impact of single particles with high mass and energy (HZE-particles) on seeds was developed. Subdivision into LET-groups showed a remarkable contribution of an intermediate group (LET = 35 to 100 keV/micrometer) due to medium heavy ions (Z = 6 to 10). Efficiency factors for radiation damage experimentally determined and assigned to different LET-classes were compared to radiation quality factors discussed in literature.     

Approaches to radiation guidelines for space travel.

There are obvious risks in space travel that have loomed larger than any risk from radiation. Nevertheless, NASA has maintained a radiation program that has involved maintenance of records of radiation exposure, and planning so that the astronauts' exposures are kept as low as possible, and not just within the current guidelines. These guidelines are being reexamined currently by NCRP Committee 75 because new information is available, for example, risk estimates for radiation-induced cancer and about the effects of HZE particles. Furthermore, no estimates of risk or recommendations were made for women in 1970 and must now be considered. The current career limit is 400 rem to the blood forming organs. The appropriateness of this limit and its basis are being examined as well as the limits for specific organs. There is now considerably more information about age-dependency for radiation effects and this will be taken into account. In 1973 a committee of the National Research Council made a separate study of HZE particle effects and it was concluded that the attendant risks did not pose a hazard for low inclination near-earth orbit missions. Since that time work has been carried out on the so-called microlesions caused by HZE particles and on the relative carcinogenic effect of heavy ions, including iron. A remaining question is whether the fluence of HZE particles could reach levels of concern in missions under consideration. Finally, it is the intention of the committee to indicate clearly the areas requiring further research.     

载人深空探测任务的空间环境工程关键问题

对载人深空探测过程中将遭受的太阳宇宙射线、银河宇宙射线、微重力、尘与尘暴、深空微生物等环境进行分析。对不同深空环境给航天员带来的威胁进行了探讨。从物理屏蔽防护、辐射风险的监测和预警、辐射防护药物、航天员选拨等角度对采取的措施进行了阐述。从空间辐射对航天员的损伤机理、抗辐射和微重力药物开发、空间辐射屏蔽防护结构与材料、航天服自清洁、抗微生物侵蚀材料的研发等多个角度对需要进一步开展的工作进行了讨论。     

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?     

In vitro neurotoxic effects of 1 GeV/n iron particles assessed in retinal explants.

The heavy ion component of the cosmic radiation remains problematic to the assessment of risk in manned space flight. The biological effectiveness of HZE particles has yet to be established, particularly with regard to nervous tissue. Using heavy ions accelerated at the AGS of Brookhaven National Laboratory, we study the neurotoxic effects of iron particles. We exposed retinal explants, taken from chick embryos, to determine the dose response relationships for neurite outgrowth. Morphometric techniques were used to evaluate the in vitro effects of 1 GeV/a iron particles (LET 148 keV/micrometer). Iron particles produced a dose-dependent reduction of neurite outgrowth with a maximal effect achieved with a dose of 100 cGy. Doses as low as 10-50 cGy were able to induce reductions of the neurite outgrowth as compared to the control group. Neurite generation is a more sensitive parameter than neurite elongation, suggesting different mechanism of radiation damage in our model. These results showed that low doses/fluences of iron particles could impair the retinal ganglion cells' capacity to generate neurites indicating the highly neurotoxic capability of this heavy charged particle.     

On the parameterization of the biological effect in a mixed radiation field.

The exposure of astronauts and electronics to the cosmic radiation especially to the particle component pose a major risk to all space flights. Up to now it is not possible to quantify this risk within acceptable limits of accuracy. This uncertainty is not only caused by difficulties in the more or less exact prediction of the incidence of the cosmic radiation but depends also on the problem of the quantification of the radiation field and the correlation of the biological effect. Usually the biological action of a mixed radiation field is estimated as product of the measured dose with an average quality factor, the relative biological efficiency. Because of the large variation in energy and atomic number of the cosmic particles, average values of the quality factor are not precise for risk estimation. A more appropriate way to treat the biological effects of mixed radiation is the concept of particle fluence and action cross section.     

Effects of prolonged exposure of lettuce seeds to HZE particles on orbital stations.

In a study of the biological effects of cosmic HZE particles, lettuce (Lactuca sativa) seeds were flown on the orbital stations Salyut 6 and 7 for varying periods of time (from 40 to 457 days). The dependence of the biological damage on flight duration, physical parameters and the fact of passage of an HZE particle through the seed was estimated using the criterion of the frequency of aberrant cells. The arrangement of the flight biological container Biobloc made it possible to trace the location of tracks of individual HZE particles with Z > or = 6 and LET 200 keV/um. In seeds hit by HZE particles, for all exposure times, a statistically significant much higher yield of aberrant cells and also of cells containing multiple chromosome aberrations was observed than in the control material. The frequency of aberrant cells is markedly higher (by a factor of 1,5) in seeds hit than in non-hit ones. The changes of the yield of aberrant cells as a function of the absorbed dose (3.2-63.4 mGy) and the fluence (4.8-44.2 particles/cm2) are linear for the exposure duration ranging from 40 to 457 days.     

Radiation issues for piloted Mars mission.

Man is now entering an era of colonizing the moon and exploration of Mars. The crewmembers of a piloted mission to Mars will be exposed to inner belt trapped protons, the outer trapped electrons, and the galactic cosmic radiation. In addition there is always the added risk of acute exposure to a solar particle event. Current radiation risk is estimated using the idea of absorbed dose and ICRP-26, LET-dependent quality factors. In a spacecraft with aluminum walls (2 g cm-2) at solar minimum the calculated dose equivalent is 0.73 Sv for a 406-day mission. Based on the current thinking this leads to an excess cancer mortality in a 35 year male of about 1%. About 75% of the dose equivalent is contributed by HZE particles and target fragments with average quality factors of 10.3 and 20, respectively. The entire concept of absorbed dose, quality factor, and dose equivalent as applied to such missions needs to be reexamined, in light of the fact that less than 50% of the nuclei in the body of the astronaut would have been traversed by a single GCR nuclei in the 406-day mission. Clearly, more biologically relevant information about the effects of heavy ions and target fragments is needed and fluence based risk estimation strategy developed for such long term stays in space.     

Changes in developmental capacity of artemia cyst and chromosomal aberrations in lettuce seeds flown aboard Salyut-7 (Biobloc III experiment).

This paper gives the results of investigations performed on the first container (A) of the Biobloc III experiment, flown aboard the orbital station Salyut 7 for 40 days. The space flight resulted in a decreased developmental capacity of Arterlia cysts, hit or not hit by the HZE particles. No effect was observed in cysts in bulk. A synergetic effect of microgravity and gamma pre irradiation is described. The germination of in-flight lettuce seeds was decreased. The space flight resulted also in a higher percentage of cells with chromosomal aberrations. Relations between biological response, TEL and location of HZE particles are discussed.     

Mutation induction in human lymphoid cells by energetic heavy ions.

One of the concerns for extended space flight outside the magnetosphere is exposure to galactic cosmic radiation. In the series of studies presented herein, the mutagenic effectiveness of high energy heavy ions is examined using human B-lymphoblastoid cells across an LET range from 32keV/micrometer to 190 keV/micrometer. Mutations were scored for an autosomal locus, thymidine kinase (tk), and for an X-linked locus, hypoxanthine phosphoribosyltransferase (hprt). For each of the radiations studied, the autosomal locus is more sensitive to mutation induction than is the X-linked locus. When mutational yields are expressed in terms of particle fluence, the two loci respond quite differently across the range of LET. The action cross section for mutation induction peaks at 61 keV/micrometer for the tk locus and then declines for particles of higher LET, including Fe ions. For the hprt locus, the action cross section for mutation is maximal at 95 keV/micrometer but is relatively constant across the range from 61 keV/micrometer to 190 keV/micrometer. The yields of hprt-deficient mutants obtained after HZE exposure to TK6 lymphoblasts may be compared directly with published data on the induction of hprt-deficient mutants in human neonatal fibroblasts exposed to similar ions. The action cross section for induction of hprt-deficient mutants by energetic Fe ions is more than 10-fold lower for lymphoblastoid cells than for fibroblasts.     

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.     

Performance of a simple Closed Aquatic Ecosystem (CAES) in space.

A simple Closed Aquatic Ecosystem (CAES) consisting of single-celled green algae (Chlorella pyrenoidosa, producer), a spiral snail (Bulinus australianus, consumer) and a data acquisition and control unit was flown on the Chinese Spacecraft SHENZHOU-II in January 2001 for 7 days. In order to study the effect of microgravity on the operation of CAES, a 1 g centrifuge reference group in space, a ground 1 g reference group and a ground 1 g centrifuge reference group (1.4 g group) were run concurrently. Real-time data about algae biomass (calculated from transmission light intensity), temperature, light and centrifugation of the CAES were logged at minute intervals. It was found that algae biomass of both the microgravity group and the ground 1 g-centrifuge reference group (1.4 g) fluctuated during the experiment, but the algae biomass of the 1 g centrifuge reference group in space and the ground 1 g reference group increased during the experiment. The results may be attributable to influences of microgravity and 1.4 g gravity on the algae and snails metabolisms. Microgravity is the main factor to affect the operation of CAES in space and the contribution of microgravity to the effect was also estimated. These data may be valuable for the establishment of a complex CELSS in the future.