Radiation protection standards in space.

Radiation protection standards for the individual exposed to ionizing radiation in his/her daily work have evolved over more than 50 years since the first recommendations on limits by the NCRP and the ICRP. Initial standards were based on the absence of observable harm, notably skin erythema, but have since been modified as other concerns, such as leukemia and genetic effects, became more important. More recently, the general carcinogenic effect of radiation has become the principal concern at low doses. Genetic effects are also of concern in the younger individual. Modern radiation protection practices take both of these risks into account. Quantification of these risks improves as new information emerges. The study of the Japanese survivors of the atomic bombs continues to yield new information and the recent revisions in the dosimetry are about to be completed. The special circumstances of space travel suggest approaches to limits not unlike those for radiation workers on the ground. One approach is to derive a career limit based on the risks of accident faced by many nonradiation workers in a lifetime. The career limit can be apportioned according to the type of mission. The NCRP is considering this and other approaches to the specification of radiation standards in space.     

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.     

Radiation risk during long-term spaceflight.

Cosmonauts' exposure to cosmic rays during long-term spaceflight can cause unfavorable effects in health and risk for the crew members' lives. All unfavorable effects induced by exposure should be taken into consideration for the risk estimation. They should include both the acute deterministic effects and delayed effects called stochastic. On the ground the limitation of unfavorable consequences of acute exposure is achieved by means of establishing dose limits. But in space applications this approach can't be acceptable. Establishing a fixed dose limit is adequate to introducing indefinite reserve coefficient and therefore ineffective usage of spacecraft resource. The method of radiation risk calculation caused by acute and delayed effects of cosmonauts' exposure is discussed and substantiated in the report. Peculiarities of the impact of permanent radiation sources (galactic cosmic rays and trapped radiation) and the variable one (solar cosmic rays) are taken into consideration.     

Radiation effects in space.

The radiation protection guidelines of the National Aeronautics and Space Administration (NASA) are under review by Scientific Committee 75 of the National Council Protection and Measurements. The re-evaluation of the current guidelines is necessary, first, because of the increase in information about radiation risks since 1970 when the original recommendations were made and second, the population at risk has changed. For example, women have joined the ranks of the astronauts. Two types of radiation, protons and heavy ions, are of particular concern in space. Unfortunately, there is less information about the effects on tissues and cancer by these radiations than by other radiations. The choice of Quality Factors (Q) for obtaining dose equivalents for these radiations, is an important aspect of the risk estimate for space travel. There are not sufficient data for the induction of late effects by either protons or by heavy ions. The current information suggests a RBE for the relative protons of about 1, whereas, a RBE of 20 for tumor induction by heavy ions, such as iron-56, appears appropriate. The recommendations for the dose equivalent career limits for skin and the lens of the eye have been reduced but the 30-day and annual limits have been raised.     

Radiation protection issues in galactic cosmic ray risk assessment.

Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.     

Solar cosmic rays as a specific source of radiation risk during piloted space flight.

Solar cosmic rays present one of several radiation sources that are unique to space flight. Under ground conditions the exposure to individuals has a controlled form and radiation risk occurs as stochastic radiobiological effects. Existence of solar cosmic rays in space leads to a stochastic mode of radiation environment as a result of which any radiobiological consequences of exposure to solar cosmic rays during the flight will be probabilistic values. In this case, the hazard of deterministic effects should also be expressed in radiation risk values. The main deterministic effect under space conditions is radiation sickness. The best dosimetric functional for its analysis is the blood forming organs dose equivalent but not an effective dose. In addition, the repair processes in red bone marrow affect strongly on the manifestation of this pathology and they must be taken into account for radiation risk assessment. A method for taking into account the mentioned above peculiarities for the solar cosmic rays radiation risk assessment during the interplanetary flights is given in the report. It is shown that radiation risk of deterministic effects defined, as the death probability caused by radiation sickness due to acute solar cosmic rays exposure, can be comparable to risk of stochastic effects. Its value decreases strongly because of the fractional mode of exposure during the orbital movement of the spacecraft. On the contrary, during the interplanetary flight, radiation risk of deterministic effects increases significantly because of the residual component of the blood forming organs dose from previous solar proton events. The noted quality of radiation responses must be taken into account for estimating radiation hazard in space.     

Overview of atmospheric ionizing radiation (AIR) research: SST-present.

The Supersonic Transport (SST) program, proposed in 1961, first raised concern for the exposure of pregnant occupants by solar energetic particles (SEP), and neutrons were suspected to have a main role in particle propagation deep into the atmosphere. An eight-year flight program confirmed the role of SEP as a significant hazard and of the neutrons as contributing over half of the galactic cosmic ray exposures, with the largest contribution from neutrons above 10 MeV. The FAA Advisory Committee on the Radiobiological Aspects of the SST provided operational requirements. The more recent lowering of ICRP-recommended exposure limits (1990) with the classification of aircrew as "radiation workers" renewed interest in GCR background exposures at commercial flight altitudes and stimulated epidemiological studies in Europe, Japan, Canada and the USA. The proposed development of a High Speed Civil Transport (HSCT) required validation of the role of high-energy neutrons, and this resulted in ER-2 flights at solar minimum (June 1997) and studies on effects of aircraft materials on interior exposures. Recent evaluation of health outcomes of DOE nuclear workers resulted in legislation for health compensation in year 2000 and recent European aircrew epidemiological studies of health outcomes bring renewed interest in aircraft radiation exposures. As improved radiation models become available, it is imperative that a corresponding epidemiological program of US aircrew be implemented.     

Protocol for the treatment of radiation injuries.

Despite adequate precautionary measures and high-quality safeguard devices, many accidental radiation exposures continue to occur and may pose greater risks in the future, including radiation exposure in the space environment. The medical management of radiation casualties is of major concern to health care providers. Such medical management was addressed at The First Consensus Development Conference on the Treatment of Radiation Injuries, Washington, DC, 1989. The conference addressed the most appropriate treatment for the hematopoietic and infectious complications that accompany radiation injuries and for combined radiation and traumatic/burn injuries. Based on the evidence presented at the conference, a consensus statement was formulated by expert physicians and scientists. The recommended therapies, including a suggested algorithm incorporating these recommendations for the treatment of radiation injuries, will be discussed.     

Ground-based research with heavy ions for space radiation protection.

Human exposure to ionizing radiation is one of the acknowledged potential showstoppers for long duration manned interplanetary missions. Human exploratory missions cannot be safely performed without a substantial reduction of the uncertainties associated with different space radiation health risks, and the development of effective countermeasures. Most of our knowledge of the biological effects of heavy charged particles comes from accelerator-based experiments. During the 35th COSPAR meeting, recent ground-based experiments with high-energy iron ions were discussed, and these results are briefly summarised in this paper. High quality accelerator-based research with heavy ions will continue to be the main source of knowledge of space radiation health effects and will lead to reductions of the uncertainties in predictions of human health risks. Efforts in materials science, nutrition and pharmaceutical sciences and their rigorous evaluation with biological model systems in ground-based accelerator experiments will lead to the development of safe and effective countermeasures to permit human exploration of the Solar System.     

On the radiosensitivity of man in space.

Astronauts' radiation exposure limits are based on experimental and epidemiological data obtained on Earth. It is assumed that radiation sensitivity remains the same in the extraterrestrial space. However, human radiosensitivity is dependent upon the response of the hematopoietic tissue to the radiation insult. It is well known that the immune system is affected by microgravity. We have developed a mathematical model of radiation-induced myelopoiesis which includes the effect of microgravity on bone marrow kinetics. It is assumed that cellular radiosensitivity is not modified by the space environment, but repopulation rates of stem and stromal cells are reduced as a function of time in weightlessness. A realistic model of the space radiation environment, including the HZE component, is used to simulate the radiation damage. A dedicated computer code was written and applied to solar particle events and to the mission to Mars. The results suggest that altered myelopoiesis and lymphopoiesis in microgravity might increase human radiosensitivity in space.     

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.     

Radiation-induced health effects on atmospheric flight crew members: clues for a radiation-related risk analysis.

There are few human data on low-dose-rate-radiation exposure and the consequent acute and late effects. This fact makes it difficult to assess health risks due to radiation in the space environment, especially for long-term missions. Epidemiological data on civilian flight personnel cohorts can provide information on effects due to the low-dose and low-dose rate mixed high- and low-LET radiation environment in the earth's atmosphere. The physical characteristics of the radiation environment of the atmosphere make the results of the studies of commercial flight personnel relevant to the studies of activities in space. The cooperative international effort now in progress to investigate dose reconstructions will contribute to our understanding of radiation risks for space exploration.     

RBE for non-stochastic effects.

Evidence is reviewed concerning the variation of RBE values of high-LET radiations for non-stochastic effects, generally impairment of tissue integrity and function. The RBE values are dependent on the type of radiation, the type of tissue effect and the dose rate or fractionation schedule. RBE values depend strongly on the effect considered, with high values for late effects in lung, kidney and central nervous system. RBE values generally increase with decreasing dose rate or dose per fraction. Maximum values can be derived by extrapolation on the basis of a radiobiological model. These values are denoted RBEm to distinguish them from RBEM derived for stochastic effects, e.g. carcinogenesis. Values of RBEm are generally in the range of 2 to 10 and are considerably smaller by a factor of 2 to 5 than values of RBEM for various types of stochastic effects. RBE values for effects from actual exposures to mixtures of high-LET and low-LET radiations can be derived by considering the doses received and the tissue at risk. Applications of RBEm values will yield estimates of maximum values of equivalent doses and these should only be applied for planning medical interventions if the contribution from high-LET radiation is small. The selection of Q values for radiation protection is mostly based on RBE--values and the application of Q values in cases where non-stochastic effects are important might therefore result in an overestimate of the risks of exposure.     

On the parameterization of the biological effect in a mixed radiation field.

The exposure of astronauts and electronics to the cosmic radiation especially to the particle component pose a major risk to all space flights. Up to now it is not possible to quantify this risk within acceptable limits of accuracy. This uncertainty is not only caused by difficulties in the more or less exact prediction of the incidence of the cosmic radiation but depends also on the problem of the quantification of the radiation field and the correlation of the biological effect. Usually the biological action of a mixed radiation field is estimated as product of the measured dose with an average quality factor, the relative biological efficiency. Because of the large variation in energy and atomic number of the cosmic particles, average values of the quality factor are not precise for risk estimation. A more appropriate way to treat the biological effects of mixed radiation is the concept of particle fluence and action cross section.     

Mechanisms underlying cellular radiosensitivity and R.B.E.: introductory remarks.

A general outline of the symposium titled "Mechanisms underlying cellular radiosensitivity and R.B.E." will be given in the introduction. The essential topics of molecular radiation biology are described with respect to the damage, repair and mutagenesis caused by high-LET irradiation to cellular DNA. The importance of clustered DNA lesions (locally multiply damaged sites) formed in vivo is discussed. This symposium is devoted to the mechanisms of the biological effects of radiation with high LET, especially with regard to the effects of heavy ions and neutrons which may cause possible risks in space flight, (e.g. carcinogenesis and mutagenesis). Detailed understanding of these risks, however, demands knowledge of the molecular mechanisms involved in the biological effects of high-LET radiations. Thus, it was the organizers' idea to hold a symposium dealing with primary physical and chemical events caused in cellular deoxyribonucleoproteins by densely-ionizing radiations and to relate them to track structures and energy transfer processes. The mechanisms of DNA damage were regarded from different points of view including those considering DNA repair and mutagenesis. Problems associated with cell survival and radiation protection were discussed as well. Our knowledge of the molecular mechanisms of high-LET radiation actions, however, is limited compared to what we know about low-LET radiation effects (e.g. from gamma-rays or X-rays). To emphasize this statement, I would like to summarize briefly the open questions in molecular radiation biology, what we know already about low-LET effects and what is lacking describing the effect of high-LET radiation.     

A parametric study of space radiation exposures to critical body organs for low earth orbit missions.

The geomagnetically-trapped and galactic cosmic radiation environments are two of the major sources of naturally-occurring space radiation exposure to astronauts in low earth orbit. The exposure is dependent primarily on altitude, spacecraft shielding, crew stay-times, and solar cycle effects for a 28.5 deg orbital inclination. Based on Space Shuttle experience, the calculated results of a parametric study are presented for several mission scenarios using a computerized anatomical man model and are compared with the NASA crew exposure limits for several critical body organs.     

Animal studies of life shortening and cancer risk from space radiation.

The U.S. Air Force study of the delayed effects of single, total body exposures to simulated space radiation in rhesus monkeys is now in its 21st year. Observations on 301 irradiated and 57 age-matched control animals indicate that life expectancy loss from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events can be expressed as a logarithmic function of the dose. The primary causes of life shortening are cancer and endometriosis (an abnormal proliferation of the lining of the uterus in females). Life shortening estimates permit comparison of the risk associated with space radiation exposures to be compared with that of other occupational and environmental hazards, thereby facilitating risk/benefit decisions in the planning and operational phases of manned space missions. Calculations of the relative risk of fatal cancers in the irradiated subjects reveal that the total body surface dose required to double the risk of death from cancer over a 20-year post exposure period varies with the linear energy transfer (LET) of the radiation. The ability to determine the integrated dose and LET spectrum in space radiation exposures of humans is, therefore, critical to the assessment of lifetime cancer risk.     

Cytogenetic studies of blood lymphocytes from cosmonauts after long-term space flights on Mir station.

Long-term space missions may increase risks of unfavorable consequences for cosmonauts as a result of radiation effects. This paper presents results of a study of cytogenetic damage in cosmonauts' peripheral blood lymphocytes induced by space radiation. Cultivation of lymphocytes and analysis of chromosomal aberrations were made according to generally accepted methods. It is shown that the yields of dicentrics and centric rings scored after long-term space flights are considerably higher than those scored prior to the flights. An attempt was made to assess individual doses received by cosmonauts. Individual biodosimetry doses received by cosmonauts who showed a reliable increase in the yields of chromosomal-type aberrations after their first flights were estimated to be from 0.02 to 0.28 Gy.     

γ-H2AX as a biomarker of DNA damage induced by ionizing radiation in human peripheral blood lymphocytes and artificial skin

Ionizing radiation (IR) exposure is inevitable in our modern society and can lead to a variety of deleterious effects including cancer and birth defects. A reliable, reproducible and sensitive assessment of exposure to IR and the individual response to that exposure would provide much needed information for the optimal treatment of each donor examined. We have developed a diagnostic test for IR exposure based on detection of the phosphorylated form of variant histone H2AX (γ-H2AX), which occurs specifically at sites of DNA double-strand breaks (DSBs). The cell responds to a nascent DSB through the phosphorylation of thousands of H2AX molecules flanking the damaged site. This highly amplified response can be visualized as a γ-H2AX focus in the chromatin that can be detected in situ with the appropriate antibody. Here we assess the usability of γ-H2AX focus formation as a possible biodosimeter for human exposure to IR using peripheral blood lymphocytes irradiated ex vivo and three-dimensional artificial models of human skin biopsies. In both systems, the tissues were exposed to 0.2–5 Gy, doses of IR that might be realistically encountered in various scenarios such as cancer radiotherapies or accidental exposure to radiation. Since the γ-H2AX response is maximal 30 min after exposure and declines over a period of hours as the cells repair the damage, we examined the time limitations of the useful detectability of γ-H2AX foci. We report that a linear response proportional to the initial radiation dose was obtained 48 and 24 h after exposure in blood samples and skin cells respectively. Thus, detection of γ-H2AX formation to monitor DNA damage in minimally invasive blood and skin tests could be useful tools to determine radiation dose exposure and analyze its effects on humans.     

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.