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RBE: mechanisms inferred from cytogenetics.

Cyclotron-accelerated heavy ion beams provide a fine degree of control over the physical parameters of radiation. Cytogenetics affords a view into the irradiated cell at the resolution of chromosomes. Combined they form a powerful means to probe the mechanisms of RBE. Cytogenetic studies with high energy heavy ion beams reveal three LET-dependent trends for 1) level of initial damage, 2) distribution of damage among cells, and 3) lesion severity. The number of initial breaks per unit dose increases from a low-LET plateau to a peak at approximately 180 keV/micrometer and declines thereafter. Overdispersion of breaks is significant above approximately 100 keV/micrometer. Lesion severity, indicated by the level of chromosomal fragments that have not restituted even after long repair times, increases with LET. Similar studies with very low energy 238Pu alpha particles (120 keV/micrometer) reveal higher levels of initial breakage per unit dose, fewer residual fragments and a higher level of misrepair when compared to high energy heavy ions at the same LET. These observations would suggest that track structure is an important factor in genetic damage in addition to LET.

Alpha Particles↗

Radiation dosimetry measurements during U.S. Space Shuttle missions with the RME-III.

Time-resolved radiation dosimetry measurements inside the crew compartment have been made during recent Shuttle missions with the U.S. Air Force Radiation Monitoring Equipment-III (RME-III), a portable battery-powered four-channel tissue equivalent proportional counter. Results from the first six missions are presented and discussed. Half of the missions had orbital inclinations of 28.5 degrees with the remainder at inclinations of 57 degrees or greater; altitudes ranged from 300 to 600 km. The determined dose equivalent rates ranged from 70 to 5300 microSv/day. The RME-III measurements are in good agreement with other dosimetry measurements made aboard the vehicles. Measurements indicate that medium- and high-LET particles contribute less than 2% of the particle fluence for all missions, but up to 50% of the dose equivalent, depending on the spacecraft's altitude and orbital inclination. Isocontours of fluence, dose and dose equivalent rate have been developed from measurements made during the STS-28 mission. The drift rate of the South Atlantic Anomaly is estimated to be 0.49 degrees W/yr and 0.12 degrees N/yr. The calculated trapped proton and GCR dose for the STS-28 mission was significantly lower than the measured values.

Atlantic Ocean↗

Positive visual phenomena in space: A scientific case and a safety issue in space travel.

Most astronauts on Apollo, Skylab, and MIR reported 'flashes of light' occurring in different shapes and apparently moving across the visual field, in the absence of auditory, somatosensory, or olfactory abnormal percepts. A temporal correlation with heavy nuclei or protons has been documented in space and comparable phosphenes were observed by volunteers whose eyes were exposed to accelerated heavy ions at intensities below the threshold for Cerenkov visible radiation. An interaction between heavy ions and the retina was suggested. However, the biophysics of heavy ions or protons action remains undefined, the effects on photoreceptors and neuroretina have not been differentiated, and some direct action on the visual cortex never ruled out. Phosphenes are common in migraine and are known to occur also in response to the electrical stimulation of ganglion cells (in retinas without photoreceptors), optic pathways or visual cortex, with mechanisms that bypass the chemically gated channels. Intrinsic photosensitive ganglion cells exist in the retina of teleost fish and mammals. In the hypothesis of a peculiar sensitivity to subatomic particles of the visual system, phosphenes due to the activation of processes by-passing the photoreceptors would raise questions about human safety in space. The issue is particularly relevant with experiments of increasing duration being now operative in the International Space Station (ISS) and with plans of space travel outside the geomagnetic shield. Research is in progress both in the ISS and on animal models, in the framework of the NASA/ESA actions to improve the astronauts' health in space.

Cosmic Radiation↗

Free radicals, antioxidants, and nutrition.

Radiation hazards in outer space present an enormous challenge for the biological safety of astronauts. A deleterious effect of radiation is the production of reactive oxygen species, which result in damage to biomolecules (e.g., lipid, protein, amino acids, and DNA). Understanding free radical biology is necessary for designing an optimal nutritional countermeasure against space radiation-induced cytotoxicity. Free radicals (e.g., superoxide, nitric oxide, and hydroxyl radicals) and other reactive species (e.g., hydrogen peroxide, peroxynitrite, and hypochlorous acid) are produced in the body, primarily as a result of aerobic metabolism. Antioxidants (e.g., glutathione, arginine, citrulline, taurine, creatine, selenium, zinc, vitamin E, vitamin C, vitamin A, and tea polyphenols) and antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidases) exert synergistic actions in scavenging free radicals. There has been growing evidence over the past three decades showing that malnutrition (e.g., dietary deficiencies of protein, selenium, and zinc) or excess of certain nutrients (e.g., iron and vitamin C) gives rise to the oxidation of biomolecules and cell injury. A large body of the literature supports the notion that dietary antioxidants are useful radioprotectors and play an important role in preventing many human diseases (e.g., cancer, atherosclerosis, stroke, rheumatoid arthritis, neurodegeneration, and diabetes). The knowledge of enzymatic and non-enzymatic oxidative defense mechanisms will serve as a guiding principle for establishing the most effective nutrition support to ensure the biological safety of manned space missions.

Antioxidants↗

Biosatellite II mission.

Biosatellite B was launched from Cape Kennedy, Florida, on a two-stage DELTA launch vehicle at 6:04 p.m. on 7 September, 1967. Approximately nine minutes later the 435 kg spacecraft biological laboratory was placed into a satisfactory 315 km near-circular earth orbit, successfully separated from the launch vehicle's second stage and was designated Biosatellite II. The scientific payload consisting of thirteen selected general biology and radiation experiments were subjected to planned, carefully controlled environmental conditions during 45 hours of earth-orbital flight. The decision was made to abbreviate the scheduled 3-day mission by approximately one day because of a threatening tropical storm in the recovery area, and a problem of communication with the spacecraft from the tracking stations. Highest priority was placed on recovery which was essential to obtain the scientific results on all the experiments. The operational phase of the mission came to a successful conclusion with the deorbit of the recovery capsule, deployment of the parachute system and air recovery by the United States Air Force. The 127 kg recovery capsule was returned to biology laboratories at Hickam Air Force Base, Hawaii, for disassembly and immediate inspection and analysis of the biological materials by the experimenters. It was evident immediately that the quality of the biology was excellent and this fact gave promise of a high return of scientific data. The environmental conditions provided to the experimental material in the spacecraft, provisions for experimental controls, and operational considerations are presented as they relate to interpretation of the experimental results.

Acceleration↗

Geomagnetic cutoffs: a review for space dosimetry applications.

The earth's magnetic field acts as a shield against charged particle radiation from interplanetary space, technically described as the geomagnetic cutoff. The cutoff rigidity problem (except for the dipole special case) has "no solution in closed form". The dipole case yields the Stormer equation which has been repeatedly applied to the earth in hopes of providing useful approximations of cutoff rigidities. Unfortunately the earth's magnetic field has significant deviations from dipole geometry, and the Stormer cutoffs are not adequate for most applications. By application of massive digital computer power it is possible to determine realistic geomagnetic cutoffs derived from high order simulation of the geomagnetic field. Using this technique, "world-grids" of directional cutoffs for the earth's surface and for a limited number of satellite altitudes have been derived. However, this approach is so expensive and time consuming it is impractical for most spacecraft orbits, and approximations must be used. The world grids of cutoff rigidities are extensively used as lookup tables, normalization points and interpolation aids to estimate the effective geomagnetic cutoff rigidity of a specific location in space. We review the various options for estimating the cutoff rigidity for earth-orbiting satellites.

Cosmic Radiation↗

Radiation measurements in low Earth orbit: U.S. and Russian results.

The radiation environment in low-Earth orbital flights is complex. It is strongly influenced by altitude, orbital inclination, time within a given solar cycle, flight duration, and shielding configuration. At any specified shielded location, both primary and secondary particles generated by nuclear interactions of primary particles with spacecraft structure are present. In addition, there are atmospheric secondary albedo protons and neutrons. No single detector can adequately measure this complex radiation field, and measurements of very high linear energy transfer target fragmentation products are particularly difficult. Crew radiation exposure have exclusively been measured using passive thermoluminescent detectors (TLDs). The cosmonaut exposures on the Mir station, uncorrected for the TLD inefficiency and neutron contribution, have varied from a low of 2.43 cGy to a high of 8.70 cGy. These correspond to dose rates of 144 microGy d(-1) to 468 microGy d(-1). These are consistent with rates observed by the D2 ion-chamber. Using the rates measured by the D1 chamber, dose rates under 4 cm of water vary from about 60 microGy d-1 to about 350 microGy d(-1). There is variation of about a factor of two between the dose rates at various locations in the same module. There is also a variation of dose rates of about a factor two between various modules. The highest astronaut dose for a Shuttle flight (STS-82) was 3.205 cGy with a dose rate of 3,221 microGy d(-1). Neutron contribution could be 36 +/- 15% of the astronaut charged particle dose equivalent. East-West asymmetry of dose rate is significant for spacecrafts that fly in an fixed altitude, such as the International Space Station.

Cosmic Radiation↗

The ALTEA facility on the International Space Station.

The ALTEA project studies the problems related to possible functional damage to the Central Nervous System (CNS) due to particle radiation in space environment. The project is a large international and multi-disciplinary collaboration. The ALTEA instrumentation is an helmet-shaped multi-sensor device that will measure concurrently the dynamics of the functional status of the visual system and the passage of each particle through the brain within a pre-determined energy window. ALTEA is scheduled to fly in the International Space Station in February 2003. One part of the multi-sensor device, one of the advanced silicon telescopes, will be launched in the ISS in early 2002 and serve as test for the final device and as discriminating dosimeter for the particle fluences within the ISS.

Aerospace Medicine↗

A new dynamical atmospheric ionizing radiation (AIR) model for epidemiological studies.

A new Atmospheric Ionizing Radiation (AIR) model is currently being developed for use in radiation dose evaluation in epidemiological studies targeted to atmospheric flight personnel such as civilian airlines crewmembers. The model will allow computing values for biologically relevant parameters, e.g. dose equivalent and effective dose, for individual flights from 1945. Each flight is described by its actual three dimensional flight profile, i.e. geographic coordinates and altitudes varying with time. Solar modulated primary particles are filtered with a new analytical fully angular dependent geomagnetic cut off rigidity model, as a function of latitude, longitude, arrival direction, altitude and time. The particle transport results have been obtained with a technique based on the three-dimensional Monte Carlo transport code FLUKA, with a special procedure to deal with HZE particles. Particle fluxes are transformed into dose-related quantities and then integrated all along the flight path to obtain the overall flight dose. Preliminary validations of the particle transport technique using data from the AIR Project ER-2 flight campaign of measurements are encouraging. Future efforts will deal with modeling of the effects of the aircraft structure as well as inclusion of solar particle events.

Aerospace Medicine↗

Titan's stratospheric temperature asymmetry: a radiative origin?

During the 1981 Voyager encounter, Titan's stratosphere exhibited a large thermal asymmetry, with high northern latitudes being colder than comparable southern latitudes. Given the short radiative time constant, this asymmetry would not be expected at the season of the Voyager observations (spring equinox), if the infrared and solar opacity sources were distributed symmetrically. We have investigated the radiative budget of Titan's stratosphere, using two selections of Voyager IRIS spectra recorded at symmetric northern and southern latitudes. In the region 0.1-1 mbar, temperatures are 7 K colder at 50 degrees N than at 53 degrees S and the difference reaches approximately 13 K at 5 mbar. On the other hand, the northern region is strongly enriched in nitriles and hydrocarbons, and the haze optical depth derived from the continuum emission between 8 and 15 micrometers is twice as large as in the south. Cooling rate profiles have been computed at the two locations, using the gas and haze abundances derived from the IRIS measurements. We find that, despite lower temperatures, the cooling rate profiles in the pressure range 0.15-5 mbar are 20 to 40% larger in the north than in the south, because of the enhanced concentrations of infrared radiators. Because the northern hemisphere appears darker than the southern one in the Voyager images, enhanced solar heating is also expected to take place at 50 degrees N. Solar heating rate profiles have been calculated, with two different assumptions on the origin of the hemispheric asymmetry. In the most likely case where it results from a variation in the absorbance of the haze material, the heating rates are found to be 12-15% larger at the northern location than at the southern one, a smaller increase than that in the cooling rates. If the lower albedo in the north results from an increase in the particle number density, a 55 to 75% difference is found for the pressure range 0.15-5 mbar, thus larger than that calculated for the cooling rates. Considering the uncertainties in the haze model, dynamical heat transport may significantly contribute to the meridional temperature gradients observed in the stratosphere. On the other hand, the latitudinal variation in gas and haze composition may be sufficient to explain the entire temperature asymmetry observed, without invoking a lag in the thermal response of the atmosphere due to dynamical inertia.

Atmosphere↗

[Survivability and morphologic anomalies in higher plants wolffia arrhiza following exposure to heavy ions of the galactic space radiation].

Experimental data on the effects of spaceflight factors, space radiation in particular, on higher plant Wolffia arrhiza firstly exposed in the "Bioblock" assembly and measurements made by physical track detectors of heavy ions (HI) are presented. Death of individual Wolffia plants and morphologic anomalies were the basic evaluation criteria. The peculiar feature of this biological object consists in the possibility to reveal delayed effects after 1-2 months since space flight as Wolffia has a high rate of vegetative reproduction. German investigators through microscopic examination of track detectors performed identification of individual plants affected by HI. With specially developed software and a coordinate system of supposition of biolayers and track detectors with the accuracy of 1 micron, tracks and even separate sections of individual HI tracks were determined in biological objects. Thereafter each Wolffia plant hit by HI was examined and data were compared with other variants. As a result, correlation between Wolffia death rate and morphologic anomalies were determined at different times post flight and topography of HI tracks was found. It is hypothesized that morphological anomalies in Walffia were caused by direct hits of plant germs by heavy ions or close passage of particles.

Apoptosis↗

Fluxes of galactic iron nuclei and associated HZE secondaries, and resulting radiation doses, in the brain of an astronaut.

Although galactic iron nuclei constitute only a small percentage of the total flux of radiation in space, they are extremely significant from a biological standpoint, and represent a concern for long-term manned space missions of the future. Dosages resulting from iron nuclei, and the high-charge secondary nuclei subsequently produced in nuclear fragmentation reactions, have been calculated at the centre of a simple model of the human brain, shielded by various thicknesses of aluminium. Three mission scenarios are considered representing different geomagnetic shielding conditions at solar minimum. Without artificial shielding absorbed dose rates outside the magnetosphere, in polar orbit and in the proposed Space Station orbit, are approximately 0.3, 0.1 and 0.03 cGy/year respectively, corresponding to dose equivalent rates of 8.0, 2.5 and 0.8 cSv/year, and decreasing by roughly a factor of two behind 10 g/cm2 of aluminium. In line with new approaches to risk estimation based on particle fluence and track structure, calculations of the number of cell nuclei likely to be struck by these HZE particles are also presented. Behind 10 g/cm2 of aluminium, 3.4%, 1.3% and 0.5% of cell nuclei at the centre of the brain will be traversed at least once by such a particle within three years, for the three mission scenarios respectively.

Brain↗

Protection of the public in situations of prolonged radiation exposure. The application of the Commission's system of radiological protection to controllable radiation exposure due to natural sources and long-lived radioactive residues.

This report provides guidance on the application of the ICRP system of radiological protection to prolonged exposure situations affecting members of the public. It addresses the general application of the Commission's system to the control of prolonged exposures resulting from practices and to the undertaking of interventions in prolonged exposure situations. Additionally, it provides recommendations on generic reference levels for such interventions. The report also considers some specific situations and discusses a number of issues that have been of concern, namely: natural radiation sources that may give rise to high doses; the restoration and rehabilitation of sites where human activities involving radioactive substances have been carried out; the return to 'normality' following an accident that has released radioactive substances to the environment; and the global marketing of commodities for public consumption that contain radioactive substances. Annexes provide some examples of prolonged exposure situations and discuss the radiological protection quantities, radiation-induced health effects and aspects of the Commission's system of radiological protection relevant to prolonged exposure. Quantitative recommendations for prolonged exposures are provided in the report. They must be interpreted with extreme caution; Chapters 4 and 5 stress the upper bound nature of the following values: Generic reference levels for intervention, in terms of existing total annual doses, are given as < approximately 100 mSv, above which intervention is almost always justifiable (situations for which the annual dose threshold for deterministic effects in relevant organs is exceeded will almost always require intervention), and < approximately 10 mSv, below which intervention is not likely to be justifiable (and above which it may be necessary). Intervention exemption levels for commodities, especially building materials, are expressed as an additional annual dose of approximately 1 mSv. The dose limit for exposures of the public from practices is expressed as aggregated (prolonged and transitory) additional annual doses from all relevant practices of 1 mSv. Dose constraints for sources within practices are expressed as an additional annual dose lower than 1 mSv (e.g. of approximately 0.3 mSv), which could be approximately 0.1 mSv for the prolonged exposure component. An exemption level for practices is expressed as an additional annual dose of approximately 0.01 mSv.

Cosmic Radiation↗

Radiogenic transformation of human mammary epithelial cells in vitro.

Cancer induction by space radiations is a major concern for manned space exploration. Accurate assessment of radiation risk at low doses requires basic understanding of mechanism(s) of radiation carcinogenesis. For determining the oncogenic effects of ionizing radiation in human epithelial cells, we transformed a mammary epithelial cell line (185B5), which was immortalized by benzo(a)pyrene, with energetic heavy ions and obtained several transformed clones. These transformed cells showed growth properties on Matrigel similar to human mammary tumor cells. To better understand the mechanisms of radiogenic transformation of human cells, we systematically examined the alterations in chromosomes and cancer genes. Among 16 autosomes examined for translocations, by using fluorescence in situ hybridization (FISH) technique, chromosomes 3, 12, 13, 15, 16, and 18 appeared to be normal in transformed cells. Chromosomes 1, 4, 6, 8, and 17 in transformed cells, however, showed patterns different from those in nontransformed cells. Southern blot analyses indicated no detectable alterations in myc, ras, Rb, or p53 genes. Further studies of chromosome 17 by using in situ hybridization with unique sequence p53 gene probe and a centromere probe showed no loss of p53 gene in transformed cells. Experimental results from cell fusion studies indicated that the transforming gene(s) is recessive. The role of genomic instability and tumor suppressor gene(s) in radiogenic transformation of human breast cells remains to be identified.

Breast↗

MEP (Mars Environment Package): toward a package for studying environmental conditions at the surface of Mars from future lander/rover missions.

In view to prepare Mars human exploration, it is necessary to promote and lead, at the international level, a highly interdisciplinary program, involving specialists of geochemistry, geophysics, atmospheric science, space weather, and biology. The goal of this program will be to elaborate concepts of individual instruments, then of integrated instrumental packages, able to collect exhaustive data sets of environmental parameters from future landers and rovers of Mars, and to favour the conditions of their implementation. Such a program is one of the most urgent need for preparing human exploration, in order to develop mitigation strategies aimed at ensuring the safety of human explorers, and minimizing risk for surface operations. A few main areas of investigation may be listed: particle and radiation environment, chemical composition of atmosphere, meteorology, chemical composition of dust, surface and subsurface material, water in the subsurface, physical properties of the soil, search for an hypothesized microbial activity, characterization of radio-electric properties of the Martian ionosphere. Scientists at the origin of the present paper, already involved at a high degree of responsibility in several Mars missions, and actively preparing in situ instrumentation for future landed platforms (Netlander--now cancelled, MSL-09), express their readiness to participate in both ESA/AURORA and NASA programs of Mars human exploration. They think that the formation of a Mars Environment working group at ESA, in the course of the AURORA definition phase, could act positively in favour of the program, by increasing its scientific cross-section and making it still more focused on human exploration.

Atmosphere↗

Radiation dose rates in Space Shuttle as a function of atmospheric density.

Current models of the inner trapped belt describe the radiation environment at times of solar minimum and solar maximum, respectively. These two models were constructed using data acquired prior to 1970 during a small solar cycle, and no valid model for the past two high solar cycles exists. There is a clear need to accurately predict the radiation exposure of astronauts at all times between the solar minimum and solar maximum, not only on the short duration Space Shuttle flights, but on the longer term stay onboard the Mir orbital station and the planned International Space Station (ISS). An analysis of the trapped absorbed dose rate, D, at six fixed locations in the habitable volume of the Shuttle shows a power law relationship, D=A rho-n, where rho is the atmospheric density, rho. The index, n, is weakly dependent on the shielding, decreasing as the average shielding increases. A better representation is provided by D=A tan-1 [(Xi-Xi c)/(Xi c-Xi m)], where Xi=ln(rho), and A, Xi c, and Xi m are constants. Xi c is related to the atmospheric density near the altitude of atmospheric cutoff. These relationships hold over nearly four decades of density variation and throughout the solar cycle. This then provides a method of calculating absorbed dose rate at anytime in the solar cycle. These empirically derived relations were used to predict the dose rates for eleven Space Shuttle flights carried out since January 1997. The predictions are in excellent agreement with measured values. This method reduces the uncertainties of a factor of about 2 for the AP-8 MIN/MAX models to less than 30%.

Altitude↗

On the biological problems to be attacked with a series of U.S. satellites in 1966.

In the opinion of interested biologists in the U.S. the search for extraterrestrial life is by far the outstanding biological task that can be undertaken with the new technology of spacecraft. And it is their hope that the bulk of the national effort put into biology in space will be directed towards the biological exploration of Mars. There are, however, many other issues that the biologist can and should pursue in orbiting laboratories, or satellites. 1) Some of these are in the areas of the cardiovascular and neurophysiology of primates, and derive their importance from the need to put man into the weightless state for prolonged durations. 2) Other questions, similarly prompted by the prospect of prolonged space flight, concern the radiation hazard. Many experiments are planned for a single satellite in which it is hoped to discover whether the weightless state significantly affects biological responses to radiation. If, as is expected, there is no synergism between weightlessness and radiation, it will be possible to pursue all other questions about radiation effects in space by experimentation on the ground. 3) Two other classes of questions that satellite experiments may answer have deeper roots in theoretical and cellular physiology. The first of these concerns weightlessness itself. A long list of experiments involving a diversity of material from animal eggs to higher plants will seek to determine whether or not the absence of a gravitational input to the system significantly affects its general performance. Special interest in the U.S. attaches to suggestions from ground based experiments that normal morphogenesis may fail in plant systems that are exposed to less than about 10(-5) g. 4) It is also hoped that satellite experiments will help resolve the long-standing debate on the cause of persistent daily rhythmicity in organisms. One school of workers in the U.S. continues to believe that such rhythmicity is caused by organisms sensing an unidentified physical variable with a 24 hr period and hence presumably caused by the earth's rotation. It is proposed to assay the persistence and stability of such rhythms in organisms orbiting the earth with a period of about 90 min. Persistence of the rhythm in such orbital conditions would dispose of the theory of external causation; failure of such rhythms to persist would, however, constitute strong though not crucial support in its favor.

Animals↗

Cell inactivation, repair and mutation induction in bacteria after heavy ion exposure: results from experiments at accelerators and in space.

To understand the mechanisms of accelerated heavy ions on biological matter, the responses of spores of B. subtilis to this structured high LET radiation was investigated applying two different approaches. 1) By the use of the Biostack concept, the inactivation probability as a function of radial distance to single particles' trajectory (i.e. impact parameter) was determined in space experiments as well as at accelerators using low fluences of heavy ions. It was found that spores can survive even a central hit and that the effective range of inactivation extends far beyond impact parameters where inactivation by delta-ray dose would be effective. Concerning the space experiment, the inactivation cross section exceeds those from comparable accelerator experiments by roughly a factor of 20. 2) From fluence effect curves, cross sections for inactivation and mutation induction, and the efficiency of repair processes were determined. They are influenced by the ions characteristics in a complex manner. According to dependence on LET, at least 3 LET ranges can be differentiated: A low LET range (app. < 200 keV/micrometers), where cross sections for inactivation and mutation induction follow a common curve for different ions and where repair processes are effective; an intermediate LET range of the so-called saturation cross section with negligible mutagenic and repair efficiency; and a high LET range (>1000 keV/micrometers) where the biological endpoints are majorly dependent on atomic mass and energy of the ion under consideration.

Bacillus subtilis↗