Estimates of HZE particle contributions to SPE radiation exposures on interplanetary missions.

Estimates of radiation doses resulting from possible HZE (high energy heavy ion) components of solar particle events (SPEs) are presented for crews of manned interplanetary missions. The calculations assume a model spectrum obtained by folding measured solar flare HZE particle abundances with the measured energy spectra of SPE alpha particles. These hypothetical spectra are then transported through aluminum spacecraft shielding. The results, presented as estimates of absorbed dose and dose equivalent, indicate that HZE components by themselves are not a major concern for crew protection but should be included in any overall risk assessment. The predictions are found to be sensitive to the assumed spectral hardness parameters.     

Radiation safety standards: space hazards vs. terrestrial hazards.

The standards currently recommended for use in space travel were perhaps the first risk derived recommendations for dose limitations developed for quasi-occupational circumstances. They were based on data, considerations, and philosophy existing prior to 1970 and considered carcinogenesis primarily. In the intervening twelve years, not only has radiation risk information improved markedly but considerations relating to risk in general have become better known. The earlier recommendations have been examined with respect to changes in risk estimation and it is noted that the same philosophy used today, would probably lead to different dose limitations. However, other philosophies might be used; in particular a comparison of risks between terrestrial occupational radiation circumstances and also with fatal accident rates in a range of industries can be made and might be used in a modified philosophy with respect to risks from carcinogenesis. Developments have also taken place with respect to the knowledge of the biological effects of HZE particles but whether these effects are limiting as compared with radiation induced carcinogenesis is not yet clear. More studies on the effects of HZE particles, now becoming available, are needed. It is recommended that an in depth reexamination be undertaken of the biological effectiveness of space radiations and the philosophy of dose limitations in comparison with other risks.     

Countermeasures for space radiation induced adverse biologic effects

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

The effects of proton exposure on neurochemistry and behavior.

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

Operant responding following exposure to HZE particles and its relationship to particle energy and linear energy transfer

On exploratory class missions astronauts will be exposed to a variety of heavy particles (HZE particles) which differ in terms of particle energy and particle linear energy transfer. The present experiments were designed to evaluate how these physical characteristics of different particles affect cognitive performance, specifically operant responding. Following exposure to ²⁸Si, ⁴⁸Ti, ¹²C and ¹⁶O particles at the NASA Space Radiation Laboratory rats were tested for their ability to respond appropriately to changes in reinforcement schedules using an operant task. The results showed that the effectiveness of different particles in disrupting cognitive performance, defined as the lowest dose that produced a performance decrement, varied as a function of the energy of the specific particle: for comparisons between different energies of the same particle (e.g., ⁵⁶Fe) the effectiveness of the particle was directly proportional to particle linear energy transfer, whereas for comparisons between different particles (e.g., ⁵⁶Fe and ¹⁶O) effectiveness was inversely proportional to particle linear energy transfer. The results are discussed in terms of the mechanisms that influence the effectiveness of different particles and energies and in terms of their implications for analyzing the possible risks to astronauts of decrements in cognitive performance following exposure to HZE particles on long-duration exploratory class missions.     

Radiation issues for piloted Mars mission.

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

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.     

Strategies for dealing with solar particle events in missions beyond the magnetosphere.

For long duration missions beyond the magnetosphere, the hazards posed by solar particle events (SPE) require the development of new strategies to minimize both the radiation dose and the effects. Potential strategies include the development of improved short-term forecasting of SPE through better observations and research, consideration of HZE particles in real-time forecasting and monitoring, improved knowledge of the biological effects of the particles involved in SPE, and the development of methods for combining SPE forecasts with temporary shielding and chemical countermeasures. Evaluation of present capabilities and the identification of areas of further research to achieve the necessary capabilities are discussed.     

Radiation environments and absorbed dose estimations on manned space missions.

In order to make an assessment of radiation risk during manned missions in space, it is necessary first to have as accurate an estimation as possible of the radiation environment within the spacecraft to which the astronauts will be exposed. Then, with this knowledge and the inclusion of body self-shielding, estimations can be made of absorbed doses for various body organs (skin, eye, blood-forming organs, etc.). A review is presented of our present knowledge of the radiation environments and absorbed doses expected for several space mission scenarios selected for our development of the new radiation protection guidelines. The scenarios selected are a 90-day mission at an altitude (450 km) and orbital inclinations (28.5 degrees, 57 degrees and 90 degrees) appropriate for NASA's Space Station, a 15-day sortie to geosynchronous orbit and a 90-day lunar mission. All scenarios chosen yielded dose equivalents between five and ten rem to the blood forming organs if no large solar particle event were encountered. Such particle events could add considerable exposure particularly to the skin and eye for all scenarios except the one at 28.5 degrees orbital inclination.     

Unique biological aspects of radiation hazards--an overview.

Low orbit, geostationary, and deep-space flights differ from one another with respect to particle radiation environment, participating population size, mission duration, and biological risks other than radiation. It is proposed that all of these factors be considered in the setting of safety standards and, in particular, that the rem-dose concept is applicable only to radiations having low and intermediate linear energy transfer (electrons, protons, and helium ions), whereas the incidence of microlesions is a more meaningful indicator of the hazard due to higher-Z, high energy (HZE) particles. A microlesion is the biological injury inflicted in a specific tissue by a single HZE particle, and it is still in need of quantitative biological definition for specific mammalian tissues. If for example, a microlesion is taken as due to a HZE particle track 10 cell diameters long with LET > 200 KeV/micrometer in its core and > 25 rad dose in its penumbra at a distance of 10 micrometers, then the microlesion dose rate in geostationary orbit, for example, is about 9,000 microlesions per cm3 of tissue per month.     

Simulations of MATROSHKA experiment outside the ISS using PHITS

The radiation environment at the altitude of the International Space Station (ISS) is substantially different than anything typically encountered on Earth in both the character of the radiation field and the significantly higher dose rates. Concerns about the biological effects on humans of this highly complex natural radiation field are increasing due to higher amount of astronauts performing long-duration missions onboard the ISS and especially if looking into planned future manned missions to Mars. In order to begin the process of predicting the dose levels seen by the organs of an astronaut, being the prerequisite for radiation risk calculations, it is necessary to understand the character of the radiation environment both in- and outside of the ISS as well as the relevant contributions from the radiation field to the organ doses.     

Summary of current radiation dosimetry results on manned spacecraft.

Measurements of radiation exposures aboard manned space flights of various altitudes, orbital inclinations and durations were performed by means of passive radiation detectors, thermoluminescent detectors (TLD's), and in some cases by active electronic counters. The TLD's and electronic counters covered the lower portion of the LET (linear energy transfer) spectra, while the nuclear track detectors measured high-LET produced by HZE particles. In Spacelab (SL-1), TLD's recorded a range of 102 to 190-millirad, yielding an average low-LET dose rate of 11.2 mrad per day inside the module, about twice the dose rate measured on previous space shuttle flights. Because of a higher inclination of the SL-1 orbit (57 degrees versus 28.5 degrees for previous shuttle flights), substantial fluxes of highly ionizing HZE particles were also observed, yielding an overall average mission dose-equivalent of about 135 millirem, about three times higher than measured an previous shuttle missions. A dose rate more than an order of magnitude higher than for any other space shuttle light was obtained for mission STS-41C, reflecting the highest orbital altitude to date of 519 km.     

Microlesions: theory and reality.

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

Effect of HZE particles and space hadrons on bacteriophages.

The effect of high energy (HZE) particles and high energy hadrons on T4Br+ bacteriophage was analyzed. The experiments were done in orbital flight, on high mountains, on an accelerator, and with an alpha particle source. We studied the survival rate of the bacteriophage, the mutation frequency, the mutation spectrum and the revertability under the action of chemical mutagens with a known mechanism of action on DNA. It was found that the biological efficiency of HZE particles and high energy hadrons is greater than that of gamma radiation. The spectra of mutations produced by these mutations and the mechanisms of their action are also different. These effects were local, because of the mode of interaction of the radiant energy with biological objects, and depended on the linear energy transfer (LET). The modes have now been experimentally defined.     

Radiation risk estimation and its application to human beings in space.

The number of human beings likely to spend time in space will increase as time goes on. While exposures vary according to missions, orbits, shielding, etc., an average space radiation fluence (ignoring solar flares, radiation belts and anomalous regions in space) in locations close to earth is about 10 rad/year with a quality factor of about 5.5. The potential effects of exposure to these fluences include both non-stochastic effects and stochastic effects (cancer and genetic damage). Non-stochastic effects, damage to the lens of the eye, bone marrow or gonads, can be avoided by keeping radiation limits below threshold values. Stochastic effects imply risk at all levels. The magnitude of these risks has been discussed in a number of reports by the UNSCEAR Committee and the BEIR Committee in the USA during 1970-1980. The uncertainties associated with these risks and information which has become available since the last BEIR report is discussed. In considering reasonable limits for exposure in space, acceptable levels for stochastic risks must be based on appropriate comparisons. In view of the limited term of duty of most space workers, a lifetime limit may be appropriate. This lifetime limit might be comparable in terms of risks with limits for radiation workers on the ground but received at a higher annual rate for a shorter time. These and other approaches are expected to be considered by an NCRP Committee currently examining the problem of space radiation hazards.     

Embryogenesis and organogenesis of Carausius morosus under spaceflight conditions

The influence of cosmic radiation and/or microgravity on insect development was studied during the 7 day German Spacelab Mission D1. Eggs of Carausius morosus of five stages differing in sensitivity to radiation and in capacity to regeneration were allowed to continue their development in the BIORACK 22°C incubator, either at microgravity conditions or on the 1 g reference centrifuge. Using the Biostack concept - eggs in monolayers were sandwiched between visual track detectors - and the 1 g reference centrifuge, we were able to separate radiation effects from microgravity effects and also from combined effects of these two factors in space. After retrieval, hatching rates, growth kinetics and anomaly frequencies were determined in the different test samples. The early stages of development turned out to be highly sensitive to single hits of cosmic ray particles as well as to the temporary exposure to microgravity during their development. In some cases, the combined action of radiation and microgravity even amplified the effects exerted by the single parameters of space. Hits by single HZE particles caused early effects, such as body anomalies, as well as late effects, such as retarded growth after hatching. Microgravity exposure lead to a reduced hatching rate. A synergistic action of HZE particle hits and microgravity was established in the unexpectedly high frequency of anomal larvae. However, it cannot be excluded, that cosmic background radiation or low LET HZE particles are also causally involved in damage observed in the microgravity samples.     

The microlesion concept in HZE particle dosimetry.

High energy, high-Z (HZE) particles are present in high-altitude and high-inclination satellite orbits. Most of the HZE dose above LET = 200 keV/micrometer is due to Fe nuclei. Individual HZE particles can damage several cells adjacent to one another along the particle track in tissue. The outcome has been described as a "microlesion" by D. Grahn. The present study attempts to define conditions for microlesions in specific tissues, to seek biological evidence that microlesions are produced, and to evaluate the microlesion as a potentially useful unit of dose in assessing hazards to spaceworkers. Microlesions in individuals cells and hair follicles have been described. Microbial studies have provided some evidence for independent secondary electron action. Whether or not a few hundred microlesions would be damaging to the whole organism depends upon the nature of damage to critical tissues. For example, cancer may occur if microlesions kill several cells in a straight line and mutate other cells alongside the particle track. Fe particle irradiation of the mouse Harderian gland (Fry et al., this issue) produces tumors efficiently. Microlesions in the lens, cornea, and retina need to be considered. Further dialogue is required before a final decision can be made concerning the most appropriate way to assess the HZE hazard.     

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

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

Possible effects of protracted exposure on the additivity of risks from space radiations.

Conventional radiation risk assessments are presently based on the additivity assumption. This assumption states that risks from individual components of a complex radiation field involving many different types of radiation can be added to yield the total risk of the complex radiation field. If the assumption is not correct, the summations and integrations performed to obtain the presently quoted risk estimates are not appropriate. This problem is particularly important in the area of space radiation risk evaluation because of the many different types of high- and low-LET radiation present in the galactic cosmic ray environment. For both low- and high-LET radiations at low enough dose rates, the present convention is that the addivity assumption holds. Mathematically, the total risk, Rtot is assumed to be Rtot = summation (i) Ri where the summation runs over the different types of radiation present. If the total dose (or fluence) from each component is such that the interaction between biological lesions caused by separate single track traversals is negligible within a given cell, it is presently considered to be reasonable to accept the additivity assumption. However, when the exposure is protracted over many cell doubling times (as will be the case for extended missions to the moon or Mars), the possibility exists that radiation effects that depend on multiple cellular events over a long time period, such as is probably the case in radiation-induced carcinogenesis, may not be additive in the above sense and the exposure interval may have to be included in the evaluation procedure. It is shown, however, that "inverse" dose-rate effects are not expected from intermediate LET radiations arising from the galactic cosmic ray environment due to the "sensitive-window-in-the-cell-cycle" hypothesis.