Genetic risks associated with radiation exposures during space flight.

The genetic risks associated with manned space flight are judged to be of little significance to the general population. The risks may be significant to the irradiated individual, particularly if one focuses attention on the incidence of dominant and chromosomal mutations that are expressed in the first generation offspring. Even so, the risk is not increased to a great extent by the low linear energy transfer (LET) component of the space radiations. It is the presumed high LET component, neutrons especially, that would make the major contribution to the risk, because the relative biological effectiveness (RBE) values for this component, relative to low dose-rate photon irradiation, are between 10 and 40, depending upon the particular genetic effect and dose-rate comparison. The appropriate RBE value would probably be 20 or greater, so that even small neutron doses become magnified in their contribution. Under the assumed condition of protracted exposure to 8 rads of low LET radiation and 2 rads of high LET radiation, or from 48 to 88 rem, the individual's risk of transmitting a new dominant mutation that will be expressed in his immediate offspring is estimated to increase by at least 4% and as much as about 40%. The HZE-particle component is not expected to make a significant contribution to the total risk.     

Uncertainties in estimates of the risks of late effects from space radiation.

Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Using the linear-additivity model for radiation risks, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain an estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including a deep space outpost and Mars missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative metrics, e.g., the number of days in space without exceeding a given risk level within well-defined confidence limits.     

Cataract analysis and the assessment of radiation risk in space.

Radiation cataract, a non-stochastic effect on the lens, is readily amenable to non-invasive analysis. Thus, it provides the means to assess radiation risk in space and for long-term monitoring of those who frequent that environment. The importance of such evaluations are underscored by the uncertainties associated with the assignment of quality factors for the effects of heavy charged particles constituting cosmic and solar radiation. Experimental studies were conducted using albino rats to evaluate the cataractogenic potential of 570 MeV/amu Argon ions administered as both single and protracted doses. The cataract studies and investigations of quantitative cytopathological changes associated with them indicate that as the dose of heavy particles decreases, the relative biological effectiveness, compared to X rays, increases. Fractionating the exposures not only failed to reduce the cataractogenic effect but caused a dose-dependent enhancement in the time of onset of opacification. Cytopathologically, the damage caused by heavy particles, when compared to low-LET radiation was found to be quantitatively dissimilar but qualitatively identical. In addition, damage which might be consistent with microlesions was not evident. The data indicates that as regards the cataractogenic potential of heavy particles at low doses an assignment of a Quality Factor (QF) of at least 40 may be in order.     

Non-subjective cataract analysis and its application in space radiation risk assessment.

Experimental animal studies and human observations suggest that the question is not whether or not prolonged space missions will cause cataracts to appear prematurely in the astronauts, but when and to what degree. Historically the major impediment to radiation cataract follow-up has been the necessarily subjective nature of assessing the degree of lens transparency. This has spurred the development of instruments which produce video images amenable to digital analysis. One such system, the Zeiss Scheimpflug slit lamp measuring system (SLC), was incorporated into our ongoing studies of radiation cataractogenesis. It was found that the Zeiss SLC measuring system has high resolution and permits the acquisition of reproducible images of the anterior segment of the eye. Our results, based on about 650 images of the rats lens, and followed over a period of 91 weeks of radiation cataract development, showed that the integrated optical density (IOD) of the lens correlated well with conventional assessment with the added advantages of objectivity, permanent and transportable records and linearity as cataracts become more severe. This continuous data acquisition, commencing with cataract onset, can proceed through more advanced stages. The SLC exhibits much greater sensitivity reflected in a continuously progressive severity despite the artifactual plateaus in staging which occur using conventional scoring methods. Systems such as the Zeiss SLC should be used to monitor astronauts frequent visits to low earth orbit to obtain a longitudinal data-base on the influence of this activity on the lens.     

Mathematical model for assessment of radiation risk on long space missions.

A mathematical model is developed which describes the dynamics of radiation-induced mortality in mammalian populations. It relates statistical biometric functions with statistical characteristics and dynamics of an organism's critical system. In the framework of the model the effects of low and very low dose rates of chronic radiation on mice are simulated. Respectively, thrombocytopoietic and granulocytopoietic systems are considered as the critical ones. To calculate the dynamics of these systems, mathematical models are applied, too. In accordance with experimental data, the mortality model reproduces on quantitative level both increased and decreased mortality rates in populations of LAF1 mice, which were chronically exposed, respectively, to low and very low level radiation. All this makes it feasible to use the model as a basis for risk assessments of low level long-term irradiation.     

Uncertainties in radiation effect predictions for the natural radiation environments of space.

Future manned missions beyond low earth orbit require accurate predictions of the risk to astronauts and to critical systems from exposure to ionizing radiation. For low-level exposures, the hazards are dominated by rare single-event phenomena where individual cosmic-ray particles or spallation reactions result in potentially catastrophic changes in critical components. Examples might be a biological lesion leading to cancer in an astronaut or a memory upset leading to an undesired rocket firing. The risks of such events appears to depend on the amount of energy deposited within critical sensitive volumes of biological cells and microelectronic components. The critical environmental information needed to estimate the risks posed by the natural space environments, including solar flares, is the number of times more than a threshold amount of energy for an event will be deposited in the critical microvolumes. These predictions are complicated by uncertainties in the natural environments, particularly the composition of flares, and by the effects of shielding. Microdosimetric data for large numbers of orbits are needed to improve the environmental models and to test the transport codes used to predict event rates.     

A space radiation transport method development.

Improved spacecraft shield design requires early entry of radiation constraints into the design process to maximize performance and minimize costs. As a result, we have been investigating high-speed computational procedures to allow shield analysis from the preliminary design concepts to the final design. In particular, we will discuss the progress towards a full three-dimensional and computationally efficient deterministic code for which the current HZETRN evaluates the lowest-order asymptotic term. HZETRN is the first deterministic solution to the Boltzmann equation allowing field mapping within the International Space Station (ISS) in tens of minutes using standard finite element method (FEM) geometry common to engineering design practice enabling development of integrated multidisciplinary design optimization methods. A single ray trace in ISS FEM geometry requires 14 ms and severely limits application of Monte Carlo methods to such engineering models. A potential means of improving the Monte Carlo efficiency in coupling to spacecraft geometry is given in terms of re-configurable computing and could be utilized in the final design as verification of the deterministic method optimized design.     

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.     

Secondary radiation environments in heavy space vehicles and instruments.

Secondary radiations produced by the interactions of primary cosmic rays and trapped protons with spacecraft materials and detectors provides an important, and sometimes dominant, radiation environment for sensitive scientific instruments and biological systems. In this paper the success of a number of calculations in predicting a variety of effects will be examined. The calculation techniques include Monte Carlo transport codes and semi-empirical fragmentation calculations. Observations are based on flights of the Cosmic Radiation Environment and Activation Monitor at a number of inclinations and altitudes on Space Shuttle. The Shuttle experiments included an active cosmic-ray detector as well as metal activation foils and passive detector crystals of sodium iodide which were counted for induced radioactivity soon after return to earth. Results show that cosmic-ray secondaries increase the fluxes of particles of linear energy transfer less than 200 MeV/(gm cm-2), while the activation of the crystals is enhanced by about a factor of three due to secondary neutrons. Detailed spectra of induced radioactivity resulting from spallation products have been obtained. More than a hundred significant radioactive nuclides are included in the calculation and overall close agreement with the observations is obtained.     

Models of CNS radiation damage during space flight.

The primary structural and functional arrangement of the different cell types within the CNS are reviewed. This was undertaken with a view to providing a better understanding of the complex interrelationships that may contribute to the pathogenesis of lesions in this tissue after exposure to ionizing radiation. The spectrum of possible CNS radiation-induced syndromes are discussed although not all have an immediate relevance to exposure during space flight. The specific characteristics of the lesions observed would appear to be dose related. Very high doses may produce an acute CNS syndrome that can cause death. Of the delayed lesions, selective coagulation necrosis of white matter and a later appearing vascular microangiopathy, have been reported in patients after cancer therapy doses. Lower doses, perhaps very low doses, may produce a delayed generalised CNS atrophy; this effect and the probability of the induction of CNS tumors could potentially have the greatest significance for space flight.     

Potential vascular damage from radiation in the space environment.

Cultured endothelial cells of blood vessels have a Do of 2 Gy for X-rays. A dose of 0.5 Gy of X-rays has an acute effect on vessel diameter. The vessels may show other acute effects such as change in permeability including a change in the blood brain barrier. Changes occurring from late effects of chronic exposure in vascular architecture include telangiectasia and decrease in vascular density. Changes in the perivascular connective tissue particularly collagen may play a role in these changes. After charged particle exposure of 15 and 30 Gy, radiation changes in the blood brain barrier and vascular changes are noted in the nervous system. These long term changes are recorded by PET, MRI, and CT imaging. Chronic exposure to alpha particles causes vascular damage in compact bone resulting in bone infarcts. Using tandem scanning confocal microscopy in-situ imaging of the capillaries and collagen of the papillary dermis provides a non-invasive method of serial recording of changes in irradiated microvasculature.     

Electrostatic space radiation shielding

For the success of NASA’s new vision for space exploration to Moon, Mars and beyond, exposures from the hazards of severe space radiation in deep space long duration missions is ‘a must solve’ problem. The payload penalty demands a very stringent requirement on the design of the spacecrafts for human deep space missions. The exploration beyond low Earth orbit (LEO) to enable routine access of space will require protection from the hazards of the accumulated exposures of space radiation, Galactic Cosmic Rays (GCR) and Solar Particle Events (SPE), and minimizing the production of secondary radiation is a great advantage. There is a need to look to new horizons for newer technologies. The present investigation revisits electrostatic active radiation shielding and explores the feasibility of using the electrostatic shielding in concert with the state-of-the-art materials shielding and protection technologies. The full space radiation environment has been used, for the first time, to explore the feasibility of electrostatic shielding. The goal is to repel enough positive charge ions so that they miss the spacecraft without attracting thermal electrons. Conclusions are drawn for the future directions of space radiation protection.     

The effect of space radiation of the nervous system.

The long-term effects of irradiation by accelerated heavy ions on the structure and function of the nervous system have not been studied extensively. Although the adult brain is relatively resistant to low LET radiation, cellular studies indicate that individual heavy ions can produce serious membrane lesions and multiple chromatin breaks. Capillary hemorrhages may follow high LET particle irradiation of the developing brain as high RBE effects. Evidence has been accumulating that the glial system and blood-brain barrier (BBB) are relatively sensitive to injury by ionizing radiation. While DNA repair is active in neural systems, it may be assumed that a significant portion of this molecular process is misrepair. Since the expression of cell lethality usually requires cell division, and nerve cells have an extremely low rate of division, it is possible that some of the characteristic changes of premature aging may represent a delayed effect of chromatin misrepair in brain. Altered microcirculation, decreased local metabolism, entanglement and reduction in synaptic density, premature loss of neurons, myelin degeneration, and glial proliferation are late signs of such injuries. HZE particles are very efficient in producing carcinogenic cell transformation, reaching a peak for iron particles. The promotion of viral transformation is also efficient up to an energy transfer of approximately 300 keV/micron. The RBE for carcinogenesis in nerve tissues remains unknown. On the basis of available information concerning HZE particle flux in interplanetary space, only general estimates of the magnitude of the effects of long-term spaceflight on some nervous system parameters may be constructed.     

NASA' s life sciences and space radiation biology.

Plans for the various missions in which men and women are expected to participate during the next 10 years are outlined. Such missions include flights of up to three months duration in low earth orbit as well as possible short excursions to geosynchronous orbit. Research activities are described which cover the full spectrum of physiological and psychological responses to space flight. These activities are shown to contribute to the ongoing Shuttle program and the future Space Station. The paper includes a summary of the major technical thrusts needed to support extended habitation in space.     

Instrument and spacecraft faults associated with nuclear radiation in space.

A review is given which surveys the variety of faults and failures which have occurred in space due both to the effects of single, energetic nuclear particles, as well as effects due to the accumulated ionizing dose or the fluence of nuclear particles. The review covers a variety of problems with sensors, electronics, instruments and spacecraft from several countries.     

Nuclear model calculations and their role in space radiation research.

Proper assessments of spacecraft shielding requirements and concomitant estimates of risk to spacecraft crews from energetic space radiation requires accurate, quantitative methods of characterizing the compositional changes in these radiation fields as they pass through thick absorbers. These quantitative methods are also needed for characterizing accelerator beams used in space radiobiology studies. Because of the impracticality/impossibility of measuring these altered radiation fields inside critical internal body organs of biological test specimens and humans, computational methods rather than direct measurements must be used. Since composition changes in the fields arise from nuclear interaction processes (elastic, inelastic and breakup), knowledge of the appropriate cross sections and spectra must be available. Experiments alone cannot provide the necessary cross section and secondary particle (neutron and charged particle) spectral data because of the large number of nuclear species and wide range of energies involved in space radiation research. Hence, nuclear models are needed. In this paper current methods of predicting total and absorption cross sections and secondary particle (neutrons and ions) yields and spectra for space radiation protection analyses are reviewed. Model shortcomings are discussed and future needs presented.     

Cellular changes in microgravity and the design of space radiation experiments.

Cell metabolism, secretion and cell-cell interactions can be altered during space flight. Early radiobiology experiments have demonstrated synergistic effects of radiation and microgravity as indicated by increased mutagenesis, increased chromosome aberrations, inhibited development, and retarded growth. Microgravity-induced changes in immune cell functions include reduced blastogenesis and cell-mediated, delayed-type hypersensitivity responses, increased cytokine secretions, but inhibited cytotoxic effects and macrophage differentiation. These effects are important because of the high radiosensitivity of immune cells. It is difficult to compare ground studies with space radiation biology experiments because of the complexity of the space radiation environment, types of radiation damage and repair mechanisms. Altered intracellular functions and molecular mechanisms must be considered in the design and interpretation of space radiation experiments. Critical steps in radiocarcinogenesis could be affected. New cell systems and hardware are needed to determine the biological effectiveness of the low dose rate, isotropic, multispectral space radiation and the potential usefulness of radioprotectants during space flight.     

Cellular parameters for track structure modeling of radiation hazard in space.

Based on irradiation with 45 MeV/u N and B ions and with Co-60 gamma rays, cellular parameters of Katz's track structure model have been fitted for the survival of V79-379A Chinese hamster lung fibroblasts. Cellular parameters representing neoplastic transformations in C3H10T/1/2 cells after their irradiation with heavy ion beams, taken from earlier work, were also used to model the radiation hazard in deep space, following the system for evaluating, summing and reporting occupational exposures proposed in 1967 by a subcommittee of NCRP. We have performed model calculations of the number of transformations in surviving cells, after a given fluence of heavy charged particles of initial energy 500 MeV/u, penetrating thick layers of cells. We take the product of cell transformation and survival probabilities, calculated along the path lengths of charged particles using cellular survival and transformation parameters, to represent a quantity proportional to the "radiation risk factor" discussed in the NCRP document. The "synergistic" effect of simultaneous charged particle transfers is accounted for by the "track overlap" mode inherent in the model of Katz.