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Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts
The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.
Measurements of the secondary particle energy spectra in the Space Shuttle
Measurements of the energy spectra of secondary particles produced by galactic cosmic rays and trapped protons due to the nuclear interactions of these particles with the Shuttle shielding provide a powerful tool for validating radiation transport codes. A code validated in this way can be used to better estimate the dose and dose equivalent to body organs, measurements that cannot be made directly. The principal cause of single event upsets in electronic devices in the region of the South Atlantic Anomaly is secondary particles, and even in the region of galactic cosmic radiation a significant fraction is produced by secondary particles. In this paper, we describe the first direct measurements of the energy spectra of secondary protons, deuterons, tritons, 3He and 4He produced by galactic cosmic rays inside the Space Shuttle using a charged particle spectrometer. A comparison of these spectra with radiation transport code HZETRN showed reasonably good agreement for secondary protons. However, the code seriously underestimated the flux of all other light ions. The code has been modified to include pick-up and knock-on processes. The modified code leads to good agreement for deuterons and 3He but not for other light ions. This revised code leads to about 10% higher dose equivalent than the original code under moderate shielding, if we assume that higher charge ion fluxes are correctly predicted by the model.
Measurement of differential proton spectra onboard the Space Shuttle using a thermoluminescent dosimetry system
An experimental technique that permits the extraction of orbit-averaged, differential energy spectra of trapped radiation belt protons using simple passive detectors is described. An inversion technique is used for the data analysis. The basic principle of the described system is measurement of the energy deposited in six thermoluminescent (TLD) detector assemblies behind various spherical absorbers. The technique has been applied to a detector assembly flown on four Shuttle flights. Although severe restraints were placed on the flight package, the differential energy spectra derived from these measurements are in good agreement with analytical results using a modified trapped proton environment model. The technique shows good promise for measuring the spectra in low inclination orbits where the flux of high energy galactic cosmic rays protons is small. Modifications to the detector assembly to improve the accuracy and to extend the range of the system to higher energies are suggested.
Space motion sickness preflight adaptation training: preliminary studies with prototype trainers
Preflight training frequently has been proposed as a potential solution to the problem of space motion sickness. The paper considers successively the otolith reinterpretation, the concept for a preflight adaptation trainer and the research with the Miami University Seesaw, the Wright Patterson Air-Force Base Dynamic Environment Simulator and the Visually Coupled Airborne Systems Simulator prototype adaptation trainers.
Modeling transport kinetics in clinoptilolite-phosphate rock systems
Nutrient release in clinoptilolite-phosphate rock (Cp-PR) systems occurs through dissolution and cation-exchange reactions. Investigating the kinetics of these reactions expands our understanding of nutrient release processes. Research was conducted to model transport kinetics of nutrient release in Cp-PR systems. The objectives were to identify empirical models that best describe NH4, K, and P release and define diffusion-controlling processes. Materials included a Texas clinoptilolite (Cp) and North Carolina phosphate rock (PR). A continuous-flow thin-disk technique was used. Models evaluated included zero order, first order, second order, parabolic diffusion, simplified Elovich, Elovich, and power function. The power-function, Elovich, and parabolic-diffusion models adequately described NH4, K, and P release. The power-function model was preferred because of its simplicity. Models indicated nutrient release was diffusion controlled. Primary transport processes controlling nutrient release for the time span observed were probably the result of a combination of several interacting transport mechanisms.
Radiation-induced chromosomal instability in human mammary epithelial cells
Karyotypes of human cells surviving X- and alpha-irradiation have been studied. Human mammary epithelial cells of the immortal, non-tumorigenic cell line H184B5 F5-1 M/10 were irradiated and surviving clones isolated and expanded in culture. Cytogenetic analysis was performed using dedicated software with an image analyzer. We have found that both high- and low-LET radiation induced chromosomal instability in long-term cultures, but with different characteristics. Complex chromosomal rearrangements were observed after X-rays, while chromosome loss predominated after alpha-particles. Deletions were observed in both cases. In clones derived from cells exposed to alpha-particles, some cells showed extensive chromosome breaking and double minutes. Genomic instability was correlated to delayed reproductive death and neoplastic transformation. These results indicate that chromosomal instability is a radiation-quality-dependent effect which could determine late genetic effects, and should therefore be carefully considered in the evaluation of risk for space missions.
Consideration in selecting crops for the human-rated life support system: a Linear Programming model
A Linear Programming model has been constructed which aids in selecting appropriate crops for CELSS (Controlled Environment Life Support System) food production. A team of Controlled Environment Agriculture (CEA) faculty, staff, graduate students and invited experts representing more than a dozen disciplines, provided a wide range of expertise in developing the model and the crop production program. The model incorporates nutritional content and controlled-environment based production yields of carefully chosen crops into a framework where a crop mix can be constructed to suit the astronauts' needs. The crew's nutritional requirements can be adequately satisfied with only a few crops (assuming vitamin mineral supplements are provided) but this will not be satisfactory from a culinary standpoint. This model is flexible enough that taste and variety driven food choices can be built into the model.
NASA's Advanced Life Support Systems Human-Rated Test Facility
Future NASA missions to explore the solar system will be long-duration missions, requiring human life support systems which must operate with very high reliability over long periods of time. Such systems must be highly regenerative, requiring minimum resupply, to enable the crews to be largely self-sufficient. These regenerative life support systems will use a combination of higher plants, microorganisms, and physicochemical processes to recycle air and water, produce food, and process wastes. A key step in the development of these systems is establishment of a human-rated test facility specifically tailored to evaluation of closed, regenerative life supports systems--one in which long-duration, large-scale testing involving human test crews can be performed. Construction of such a facility, the Advanced Life Support Program's (ALS) Human-Rated Test Facility (HRTF), has begun at NASA's Johnson Space Center, and definition of systems and development of initial outfitting concepts for the facility are underway. This paper will provide an overview of the HRTF project plan, an explanation of baseline configurations, and descriptive illustrations of facility outfitting concepts.
Johnson Space Center's Regenerative Life Support Systems Test Bed
The Regenerative Life Support Systems (RLSS) Test Bed at NASA's Johnson Space Center is an atmospherically closed, controlled environment facility for human testing of regenerative life support systems using higher plants in conjunction with physicochemical life support systems. The facility supports NASA's Advanced Life Support (ALS) Program. The facility is comprised of two large scale plant growth chambers, each with approximately 11 m2 growing area. The root zone in each chamber is configurable for hydroponic or solid media plant culture systems. One of the two chambers, the Variable Pressure Growth Chamber (VPGC), is capable of operating at lower atmospheric pressures to evaluate a range of environments that may be used in a planetary surface habitat; the other chamber, the Ambient Pressure Growth Chamber (APGC) operates at ambient atmospheric pressure. The air lock of the VPGC is currently being outfitted for short duration (1 to 15 day) human habitation at ambient pressures. Testing with and without human subjects will focus on 1) integration of biological and physicochemical air and water revitalization systems; 2) effect of atmospheric pressure on system performance; 3) planetary resource utilization for ALS systems, in which solid substrates (simulated planetary soils or manufactured soils) are used in selected crop growth studies; 4) environmental microbiology and toxicology; 5) monitoring and control strategies; and 6) plant growth systems design. Included are descriptions of the overall design of the test facility, including discussions of the atmospheric conditioning, thermal control, lighting, and nutrient delivery systems.
Mission simulation as an approach to develop requirements for automation in Advanced Life Support Systems
This paper examines mission simulation as an approach to develop requirements for automation and robotics for Advanced Life Support Systems (ALSS). The focus is on requirements and applications for command and control, control and monitoring, situation assessment and response, diagnosis and recovery, adaptive planning and scheduling, and other automation applications in addition to mechanized equipment and robotics applications to reduce the excessive human labor requirements to operate and maintain an ALSS. Based on principles of systems engineering, an approach is proposed to assess requirements for automation and robotics using mission simulation tools. First, the story of a simulated mission is defined in terms of processes with attendant types of resources needed, including options for use of automation and robotic systems. Next, systems dynamics models are used in simulation to reveal the implications for selected resource allocation schemes in terms of resources required to complete operational tasks. The simulations not only help establish ALSS design criteria, but also may offer guidance to ALSS research efforts by identifying gaps in knowledge about procedures and/or biophysical processes. Simulations of a planned one-year mission with 4 crewmembers in a Human Rated Test Facility are presented as an approach to evaluation of mission feasibility and definition of automation and robotics requirements.
DNA damage and repair in oncogenic transformation by heavy ion radiation
Energetic heavy ions are present in galactic cosmic rays and solar particle events. One of the most important late effects in risk assessment is carcinogenesis. We have studied the carcinogenic effects of heavy ions at the cellular and molecular levels and have obtained quantitative data on dose-response curves and on the repair of oncogenic lesions for heavy particles with various charges and energies. Studies with repair inhibitors and restriction endonucleases indicated that for oncogenic transformation DNA is the primary target. Results from heavy ion experiments showed that the cross section increased with LET and reached a maximum value of about 0.02 micrometer2 at about 500 keV/micrometer. This limited size of cross section suggests that only a fraction of cellular genomic DNA is important in radiogenic transformation. Free radical scavengers, such as DMSO, do not give any effect on induction of oncogenic transformation by 600 MeV/u iron particles, suggesting most oncogenic damage induced by high-LET heavy ions is through direct action. Repair studies with stationary phase cells showed that the amount of reparable oncogenic lesions decreased with an increase of LET and that heavy ions with LET greater than 200 keV/micrometer produced only irreparable oncogenic damage. An enhancement effect for oncogenic transformation was observed in cells irradiated by low-dose-rate argon ions (400 MeV/u; 120 keV/micrometer). Chromosomal aberrations, such as translocation and deletion, but not sister chromatid exchange, are essential for heavy-ion-induced oncogenic transformation. The basic mechanism(s) of misrepair of DNA damage, which form oncogenic lesions, is unknown.
Human cardiovascular response to sympathomimetic agents during head-down bed rest: the effect of dietary sodium
Changes in sympathoadrenal function and cardiovascular deconditioning have long been recognized as a feature of the physiological adaptation to microgravity. The deconditioning process, coupled with altered hydration status, is thought to significantly contribute to orthostatic intolerance upon return to Earth gravity. The cardiovascular response to stimulation by sympathomimetic agents before, during, and after exposure to simulated microgravity was determined in healthy volunteers equilibrated on normal or high sodium diets in order to further the understanding of the deconditioning process.
Hypergravity signal transduction and gene expression in cultured mammalian cells
A number of studies have been conducted during space flight and with clinostats and centrifuges, suggesting that gravity effects the proliferation and differentiation of mammalian cells in vitro. However, little is known about the mechanisms by which mammalian cells respond to changes in gravitational stress. This paper summarizes studies designed to clarify the effects of hypergravity on the cultured human HeLa cells and to investigate the mechanism of hypergravity signal transduction in these cells.
The effect of dDAVP with saline loading on fluid balance during LBNP and standing after 24-hr head-down bedrest
Shuttle astronauts currently drink approximately a quart of water with eight salt tablets before reentry to restore lost body fluid and thereby reduce the likelihood of cardiovascular instability and syncope during reentry and after landing. However, the saline loading countermeasure is not entirely effective in restoring orthostatic tolerance to preflight levels. We tested the hypothesis that the effectiveness of this countermeasure could be improved with the use of a vasopressin analog, 1-deamino-8-D-arginine vasopressin (dDAVP). The rationale for this approach is that reducing urine formation with exogenous vasopressin should increase the magnitude and duration of the vascular volume expansion produced by the saline load, and in so doing improve orthostatic tolerance during reentry and postflight.
Radiogenic cell transformation and carcinogenesis
Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic mechanism(s) of radiogenic transformation of human epithelial cells.
Folic acid content in thermostabilized and freeze-dried space shuttle foods
This study was designed to determine whether freeze-dried and thermostabilized foods on a space shuttle contain adequate folate and to investigate any effects of freeze-drying on folacin. Frozen vegetables were analyzed after three states of processing: thawed; cooked; and rehydrated. Thermostabilized items were analyzed as supplied with no further processing. Measurable folate decreased in some freeze-dried vegetables and increased in others. Folacin content of thermostabilized food items was comparable with published values. We concluded that although the folacin content of some freeze-dried foods was low, adequate folate is available from the shuttle menu to meet RDA guidelines.
Space-based bacterial production of hydrogen
This paper deals with the electrochemical production of hydrogen by depolarizing the oxygen evolution reaction using human feces and urine, which contains 30-40% bacteria and yeast. The electroactivity of graphite, tungsten carbide, perovskite and RuO2-coated Ebonex (Ti4O7) as anode materials are compared. The scale-up of the process in a laboratory-scale three-dimensional packed bed cell is discussed.