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A repair/misrepair cell kinetics model is superimposed onto the track structure model of Katz to provide for a repair mechanism. The model is tested on the repair-dependent data of Yang et al. and provides an adequate description of that data. The misrepair rate determines the maximum relative biological effectiveness (RBE), but similar results could arise from indirect X-ray lethality not include in the present model.
A centrifuge with the largest diameter that can be accommodated on Space Station Freedom is required to conduct life science research in the microgravity environment of space. (This was one of the findings of a group of life scientists convened at the University of California, Davis, by Ames Research Center.) The centrifuge will be used as a research tool to understand how gravity affects biological processes; to provide an on-orbit one-g control; and to assess the efficacy of using artificial gravity to counteract the deleterious biological effect of space flight. The rationale for the recommendation and examples of using ground-based centrifugation for animal and plant acceleration studies are presented. Included are four appendixes and an extensive bibliography of hypergravity studies.
The Cytos 2 experiment was performed aboard Salyut 7 in order to test the antibiotic sensitivity of bacteria cultivated in vitro in space. An increase of the Minimal Inhibitory Concentration (MIC) in the inflight cultures (i.e., an increase of the antibiotic resistance) was observed. Complementary studies of the ultrastructure showed a thickening of the cell envelope. In order to confirm the results of the Cytos 2 experiment, we performed the ANTIBIO experiment during the D1 mission to try to differentiate, by means of the 1 g centrifuge in the Biorack, between the biological effects of cosmic rays and those caused by microgravity conditions. The originality of this experiment was in the fact that it was designed to test the antibiotic sensitivity of bacteria cultivated in vitro during the orbital phase of the flight. The results show an increase in resistance to Colistin in in-flight bacteria. The MIC is practically double in the in-flight cultures. A cell count of living bacteria in the cultures containing the different Colistin concentrations showed a significant difference between the cultures developed during space flight and the ground based cultures. The comparison between the 1 g and 0 g in-flight cultures show similar behavior for the two sets. Nevertheless, a small difference between the two sets of ground based control cultures was noted. The cultures developed on the ground centrifuge (1.4 g) present a slight decrease in comparison with the cultures developed in the static rack (1 g). In order to approach the mechanisms of the increase of antibiotic resistance on bacteria cultivated in vitro in space, we have proposed the study on penetration of antibiotics in bacterial cells in space conditions. This experiment was selected for the International Microgravity Laboratory 1 (IML-1) mission.
The Biostack experiments address especially the biological effects of the galactic particles of high atomic number and high energy, called HZE particles. The objective of the experiments is to substantiate the assessment of spaceflight radiation hazards especially regarding these particles.
The phenomenological track-structure model of cell damage is discussed. A description of the application of the track-structure model with the NASA Langley transport code for laboratory and space radiation is given. Comparisons to experimental results for cell survival during exposure to monoenergetic, heavy-ion beams are made. The model is also applied to predict cell damage rates and relative biological effectiveness for deep-space exposures.
The NASA program for determining the impact of cosmic radiation on health is described in terms of its long-term goal of reducing the uncertainty of radiation-model prediction to +/- 25 percent by 2010. The Space Radiation Health Program (SRHP) is intended to address fundamental issues for establishing a scientific basis for human radiation protection: (1) the prediction of the probability of biological effects from radiation; (2) the reduction of uncertainty in predicted highly charged energetic particles; and (3) the characterization of background flux from Galactic cosmic rays. Another key objective is to develop related technologies for ground- and space-based solar monitoring to predict events involving solar energetic particles. Although substantial uncertainties are involved in the prediction of such events, the SRHP is essential for determining crucial variables related to launching mass and humans into orbit.
Solar proton events (SPEs) occur infrequently and unpredictably, thus representing a potential hazard to interplanetary space missions. Biological damage from SPEs will be produced principally through secondary electron production in tissue, including important contributions due to delta rays from nuclear reaction products. We review methods for estimating the biological effectiveness of SPEs using a high energy proton model and the parametric cellular track model. Results of the model are presented for several of the historically largest flares using typical levels and body shielding.
An overview of galactic cosmic ray (GCR) interaction and transport methods, as implemented in the Langley Research Center GCR transport code, is presented. Representative results for solar minimum, exo-magnetospheric GCR dose equivalents in water are presented on a component by component basis for various thicknesses of aluminum shielding. The impact of proposed changes to the currently used quality factors on exposure estimates and shielding requirements are quantified. Using the cellular track model of Katz, estimates of relative biological effectiveness (RBE) for the mixed GCR radiation fields are also made.
Uncertainties in risk assessments for exposure of a Mars mission crew to space radiation place limitations on mission design and operation. Large shielding penalties are imposed in order to obtain acceptable safety margins. Galactic cosmic rays (GCR) and solar particle events (SPE) are the major concern. A warning system and 'safe-haven' are needed to protect the crew from large SPE which produce lethal doses. A model developed at NASA Johnson Space Center (JSC) to describe solar modulation of GCR intensities reduces that uncertainty to less than 10 percent. Radiation transport models used to design spacecraft shielding have large uncertainties in nuclear fragmentation cross sections for GCR which interact with spacecraft materials. Planned space measurements of linear energy transfer (LET) spectra behind various shielding thicknesses will reduce uncertainties in dose-versus-shielding thickness relationships to 5-10 percent. The largest remaining uncertainty is in biological effects of space radiation. Data on effects of energetic ions in human are nonexistent. Experimental research on effects in animals and cell is needed to allow extrapolation to the risk of carcinogenesis in humans.
Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable microcancers, arresting preneoplastic lesions, or correcting abnormal environments which predispose to high risk of malignant transformation.
Ultraviolet radiation (UVR) has provided an evolutionary challenge to life on Earth in that it is both an agent of mutation and as well as a selective force. Today surface fluxes of UVR vary diurnally, seasonally, etc. Still, the UVR flux was probably substantially higher during the early phases of evolution, suggesting that its role in evolution was even more prominent during this time. In this presentation, the creative role of UVR in evolution is discussed, specifically in connection with the role that UVR may have played in the evolution of early microbial ecosystems. The presentation will include discussions of the direct influence of UVR on such processes as photosynthesis and genetic damage, as well as the indirect influence of UVR as mediated through the production of reactive oxygen species. These biological effects of UVR will be viewed against the backdrop of the physical nature of the early Earth, surely a very different place then than now.
Measurements using silicon detectors to characterize the radiation transmitted through the EMU space suit and a human phantom have been performed using 155 and 250 MeV proton beams at LLUMC. The beams simulate radiation encountered in space, where trapped protons having kinetic energies on the order of 100 MeV are copious. Protons with 100 MeV kinetic energy and above can penetrate many centimeters of water or other light materials, so that astronauts exposed to such energetic particles will receive doses to their internal organs. This dose can be enhanced or reduced by shielding - either from the space suit or the self-shielding of the body - but minimization of the risk depends on details of the incident particle flux (in particular the energy spectrum) and on the dose responses of the various critical organs. Data were taken to characterize the beams and to calibrate the detectors using the beam in a treatment room at LLUPTF, in preparation for an experiment with the same beams incident on detectors placed in a human phantom within the EMU suit. Nuclear interactions of high-energy protons in various materials produce a small flux of highly ionizing, low-energy secondary radiation. Secondaries are of interest for their biological effects, since they cause doses and especially dose-equivalents to increase relative to the values expected simply from ionization energy loss along the Bragg curve. Because many secondaries have very short ranges, they are best measured in passive track detectors such as CR-39. The silicon detector data presented here are intended to supplement the CR-39 data in regions where silicon has greater sensitivity, in particular the portion of the LET spectrum below 5 keV/micron. The results obtained in this study suggest that optimizing the radiation shielding properties of space suits is a formidable task. The naive assumption that adding mass can reduce risk is not supported by the data, which show that reducing the dose delivered at or near the skin by low-energy particles may increase the dose delivered by energetic particles to points deeper in the body.
The unique feature of the space radiation environment is the dominance of high-energy charged particles (HZE or high LET radiation) emitted by the Sun and galactic sources, or trapped in the Van Allen radiation belts. These charged particles present a significant hazard to space flight crews, and accelerator-based experiments are underway to quantify the health risks due to unavoidable radiation exposure. There are three principal properties of charged particles that distinguish them from conventional radiation, i.e. gamma rays and x-rays. First, they have a defined range in matter rather than an exponential absorption profile. Second, they undergo nuclear reactions to produce secondary particles. Third, and most important, they deposit their energy along well-defined linear paths or tracks rather than diffuse fields. The structured energy deposition pattern interacts on multiple scales with the biological structures of DNA, cells and tissues to produce correlated patterns of damage that evade repair systems. Traditional concepts of dose and its associated normalization parameter, RBE (relative biological effectiveness), break down under experimental scrutiny, and probabilistic models of risk based on the number of particle traversals per cell may be more appropriate. Unique patterns of DNA damage, gene expression, mobilization of repair proteins, activation of cytokines and remodeling of cellular microenvironment are observed following exposure to high LET radiation. At low levels of exposure the communication of bioactive substances from irradiated to unirradiated "bystander" cells can amplify the damage and cause a significant deviation from linearity in dose vs. response relations. Under some circumstances, there is even a multigenerational delay in the expression of radiation-induced genetic damage (genomic instability) which is not strictly dose dependent. These issues and the experimental evidence derived from ground based experiments at particle accelerators are presented along with speculation about how modified inertial conditions might perturb homeostatic responses to radiation to further complicate risk assessment for space flight.
We have studied the weeping habit of Japanese flowering cherry tree in the field of Tama Forest Science Garden, Forestry and Forest Products Research Institute at the foot of Mt. Takao. Since cherry trees at various age were the materials for our plant physiology experiments, our studies were conducted in the fields where we experienced certain difficulties. Even under such difficult environment that was rather unexpected and uncontrollable, we could obtain fruitful results on the growth of cherry tree, and found them scientifically significant, especially in terms of biological effects of gravity on earth. Moreover, a lot of interesting interactions of cherry trees with various kinds of animals were observed in parallel to the plant physiology.
Interplanetary space radiation consists of fully ionized nuclei of atomic elements with high energy for which only the few lowest energy ions can be stopped in shielding materials. The health risk from exposure to these ions and their secondary radiations generated in the materials of spacecraft and planetary surface enclosures is a major limiting factor in the management of space radiation risk. Accurate risk prediction depends on a knowledge of basic radiobiological mechanisms and how they are modified in the living tissues of a whole organism. To a large extent, this knowledge is not currently available. It is best developed at ground-based laboratories, using particle accelerator beams to simulate the components of space radiation. Different particles, in different energy regions, are required to study different biological effects, including beams of argon and iron nuclei in the energy range 600 to several thousand MeV/nucleon and carbon beams in the energy range of approximately 100 MeV/nucleon to approximately 1000 MeV/nucleon. Three facilities, one each in the United States, in Germany and in Japan, currently have the partial capability to satisfy these constraints. A facility has been proposed using the Brookhaven National Laboratory Booster Synchrotron in the United States; in conjunction with other on-site accelerators, it will be able to provide the full range of heavy ion beams and energies required. International cooperation in the use of these facilities is essential to the development of a safe international space program.
PURPOSE: To investigate initial chromatid breaks in prematurely condensed G2 chromosomes following exposure to heavy ions of different LET. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (13 keV/ microm, 80 keV/microm), silicon (55 keV/microm) and iron (140 keV/microm, 185keV/microm, 440keV/microm) ions. Chromosomes were prematurely condensed using calyculin-A. Initial chromatid-type and isochromatid breaks in G2 cells were scored. RESULTS: The dose response curves for total chromatid breaks were linear regardless of radiation type. The relative biological effectiveness (RBE) showed a LET-dependent increase, peaking around 2.7 at 55-80keV/microm and decreasing at higher LET. The dose response curves for isochromatid-type breaks were linear for high-LET radiations, but linear-quadratic for gamma-rays and 13 keV/microm carbon ions. The RBE for the induction of isochromatid breaks obtained from linear components increased rapidly between 13keV/microm (about 7) and 80keV/microm carbon (about 71), and decreased gradually until 440 keV/microm iron ions (about 66). CONCLUSIONS: High-LET radiations are more effective at inducing isochromatid breaks, while low-LET radiations are more effective at inducing chromatid-type breaks. The densely ionizing track structures of heavy ions and the proximity of sister chromatids in G2 cells result in an increase in isochromatid breaks.
PURPOSE: To establish the dose-response relationship for the induction of chromosomal instability in GM10115 cells exposed to high-energy iron ions (1 GeV/nucleon, mean LET 146 keV/microm) and gold ions (11 GeV/nucleon, mean LET 1450 keV/microm). Past work has established that sparsely ionizing X-rays can induce a long-lived destabilization of chromosomes in a dose-dependent manner at an incidence of approximately 3% per gray. The present investigation assesses the capacity of High-Z and High-energy (HZE) particles to elicit this same endpoint. MATERIALS AND METHODS: Clonal populations derived from single progenitor cells surviving heavy-ion irradiation were analyzed cytogenetically to identify those clones showing a persistent destablization of chromosomes. RESULTS: Dose-response data, with a particular emphasis at low dose (< 1.0 Gy), indicate a frequency of approximately 4% per gray for the induction of chromosomal instability in clones derived from single progenitor cells surviving exposure to iron ions. The induction of chromosomal instability by gold ions was, however, less responsive to applied dose, as the observed incidence of this phenotype varied from 0 to 10% over 1-8 Gy. Both iron and gold ions gave dose-dependent increases in the yield of chromosomal aberrations (both chromosome- and chromatid-type) measured at the first mitosis following irradiation, as well as shoulderless survival curves having D0=0.87 and 1.1 Gy respectively. CONCLUSIONS: Based on the present dose-response data, the relative biological effectiveness of iron ions is 1.3 for the induction of chromosomal instability, and this indicates that heavy ions are only slightly more efficient than X-rays at eliciting this delayed phenotype.
In the Antarctic cold desert, cryptoendolithic microorganisms live under the surface of porous sandstone rocks. During the austral summer, the environment of the near-surface rock layers colonized by organisms is characterized by two kinds of temperature oscillations, both occurring across the freezing point. Low-frequency (diurnal) and large-amplitude (up to about 20 degrees C) oscillations on the sunlit surface of rocks result in a daily freeze-thaw cycle. This is a result of the diurnal changes in the sun altitude and angle with respect to the rock surface. The biological effect of this oscillation is the regulation of the onset and cessation of metabolic activity. The high-frequency (few minutes) oscillations occur only under certain weather conditions (sunny days with light winds) and are superimposed on the low-frequency oscillations. They are caused by the cooling effect of wind gusts on rock surfaces that are much warmer than ambient air temperatures. High-frequency oscillations result in a rapid freeze-thaw cycle on the surface, which, however, does not reach the microbial zone. These high-frequency freeze-thaw oscillations are probably the cause of the abiotic nature of the rock surface. Both oscillations seem to have an effect on rock weathering.