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.     

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.     

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.     

Assessment and requirements of nuclear reaction databases for GCR transport in the atmosphere and structures

The transport properties of galactic cosmic rays (GCR) in the atmosphere, material structures, and human body (self-shielding) are of interest in risk assessment for supersonic and subsonic aircraft and for space travel in low-Earth orbit and on interplanetary missions. Nuclear reactions, such as knockout and fragmentation, present large modifications of particle type and energies of the galactic cosmic rays in penetrating materials. We make an assessment of the current nuclear reaction models and improvements in these model for developing required transport code data bases. A new fragmentation data base (QMSFRG) based on microscopic models is compared to the NUCFRG2 model and implications for shield assessment made using the HZETRN radiation transport code. For deep penetration problems, the build-up of light particles, such as nucleons, light clusters and mesons from nuclear reactions in conjunction with the absorption of the heavy ions, leads to the dominance of the charge Z = 0, 1, and 2 hadrons in the exposures at large penetration depths. Light particles are produced through nuclear or cluster knockout and in evaporation events with characteristically distinct spectra which play unique roles in the build-up of secondary radiation's in shielding. We describe models of light particle production in nucleon and heavy ion induced reactions and make an assessment of the importance of light particle multiplicity and spectral parameters in these exposures.     

Development of human epithelial cell systems for radiation risk assessment.

The most important health effect of space radiation for astronauts is cancer induction. For radiation risk assessment, an understanding of carcinogenic effect of heavy ions in human cells is most essential. In our laboratory, we have successfully developed a human mammary epithelial cell system for studying the neoplastic transformation in vitro. Growth variants were obtained from heavy ion irradiated immortal mammary cell line. These cloned growth variants can grow in regular tissue culture media and maintain anchorage dependent growth and density inhibition property. Upon further irradiation with high-LET radiation, transformed foci were found. Experimental results from these studies suggest that multiexposure of radiation is required to induce neoplastic transformation of human epithelial cells. This multihits requirement may be due to high genomic stability of human cells. These growth variants can be useful model systems for space flight experiments to determine the carcinogenic effect of space radiation in human epithelial cells.     

Computational methods for reentry trajectories and risk assessment

The trajectory modeling of uncontrolled satellites close to reentry in the atmosphere is still a challenging activity. Tracking data may be sparse and not particularly accurate, the objects’ complicate shape and unknown attitude evolution may render difficult the aerodynamic computations and, last but not the least, the models used to predict the air density at the altitudes of interest, as a function of solar and geomagnetic activity, are affected by significant uncertainties.After a brief overview of the relevance of the risk related to satellite reentries and debris survival down to the ground, the paper describes some of the methods and techniques developed in support of the reentry predictions carried out for civil protection purposes. An appropriate management of the intrinsic uncertainties of the problem is in fact critical for the dissemination of the information, avoiding, as much as possible, misunderstandings and unjustified alarm.Special attention is paid to the evaluation of the risk, the availability of orbit determinations, the uncertainties of the residual lifetime estimation, and the definition of reentry and risk windows. When possible, the discussion is supported by real data, results and examples, often based on the authors’ direct experience and researches.     

Current concepts and future directions of CELSS.

Studies of bioregenerative life support systems for use in space indicate that they are scientifically feasible. Preliminary data suggest that they would provide cost- and weight-saving benefits for low Earth orbit, long duration space platforms. Concepts of such systems include the use of higher plants and/or micro-algae as sources of food, potable water and oxygen, and as sinks for carbon dioxide and metabolic wastes. Recycling of materials within the system will require processing of food organism and crew wastes using microbiological and/or physical chemical techniques. The dynamics of material flow within the system will require monitoring, control, stabilization and maintenance imposed by computers. Future phases of study will continue investigations of higher plant and algal physiology, environmental responses, and control; flight experiments for testing responses of organisms to weightlessness and increased radiation levels; and development of ground-based facilities for the study of recycling within a bioregenerative life support system.     

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.     

Biomonitoring and risk assessment on earth and during exploratory missions using AquaHab

Bioregenerative closed ecological life support systems (CELSS) will be necessary in the exploration context revitalizing atmosphere, waste water and producing food for the human CELSS mates. During these long-term space travels and stays far away from Earth in an hostile environment as well as far for example from any hospital and surgery potential, it will be necessary to know much more about chemical and drug contamination in the special sense and by human’s themselves in detail.     

Estimation and assessment of Mars contamination.

Since the beginning of the exploration of Mars, more than fourty years ago, thirty-six missions have been launched, including fifty-nine different space systems such as fly-by spacecraft, orbiters, cruise modules, landing or penetrating systems. Taking into account failures at launch, about three missions out of four have been successfully sent toward the Red Planet. The fact today is that Mars orbital environment includes orbiters and perhaps debris, and that its atmosphere and its surface include terrestrial compounds and dormant microorganisms. Coming from the UN Outer Space Treaty [United Nations Treaty on Principles Governing the Activities of States in the Exploration and Use of Outer Space, including the Moon and Other Celestial Bodies (the "Outer Space Treaty") referenced 610 UNTS 205 - resolution 2222(XXI) of December 1966] and according to the COSPAR planetary protection policy recommendations [COSPAR Planetary Protection Policy (20 October 2002), accepted by the Council and Bureau, as moved for adoption by SC F and PPP, prepared by the COSPAR/IAU Workshop on Planetary Protection, 4/02 with updates 10/0, 2002], Mars environment has to be preserved so as not to jeopardize the scientific investigations, and the level of terrestrial material brought on and around Mars theoretically has to comply with this policy. It is useful to evaluate what and how many materials, compounds and microorganisms are on Mars, to list what is in orbit and to identify where all these items are. Considering assumptions about materials, spores and gas location and dispersion on Mars, average contamination levels can be estimated. It is clear now that as long as missions are sent to other extraterrestrial bodies, it is not possible to keep them perfectly clean. Mars is one of the most concerned body, and the large number of missions achieved, on-going and planned now raise the question about its possible contamination, not necessarily from a biological point of view, but with respect to all types of contamination. Answering this question, will help to assess the potential effects of such contamination on scientific results and will address concerns relative to any ethical considerations about the contamination of other planets.     

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.     

Research on the adaptation of skeletal muscle to hypogravity: past and future directions.

Our current understanding of hypogravity-induced atrophy of skeletal muscles is based primarily on studies comparing pre- and post-flight properties of muscles. Interpretations are necessarily qualified by the assumption that the stress of reentry and readjustment to terrestrial gravity do not alter the parameters being analyzed. The neuromuscular system is highly responsive to changes in functional demands and capable of rapid adaptation, making this assumption questionable. A reexamination of the changes in the connective tissue and synaptic terminals of soleus muscles from rats orbited in biosatellites and sampled postflight indicates that these structural alterations represent adaptative responses of the atrophic muscles to the increased workload of returning to 1 G, rather than hypogravity per se. The atrophy of weightlessness is postulated to result because muscles are both underloaded and used less often. Proper testing of this hypothesis requires quantitation of muscle function by monitoring electromyography, force output and length changes during the flight. Experiments conducted in space laboratories, like those being developed for the Space Shuttle, will avoid the complications of reentry before tissue sampling and allow time course atudies of the rate of development of adaptive changes to zero gravity. Another area of great importance for future studies of muscle atrophy is inflight measurement of plasma levels of hormones and tissue receptor levels. Glucocorticoids, thyroid hormone and insulin exert dramatic regulatory influences on muscle structure. Prevention of neuromuscular atrophy becomes increasingly more important as spaceflights increase in duration. Definition of the atrophic mechanism is essential to developing means of preventing neuromuscular atrophy.     

Radiation risk and human space exploration.

Radiation protection is essential to enable humans to live and work safely in space. Predictions about the nature and magnitude of the risks posed by space radiation are subject to very large uncertainties. Prudent use of worst-case scenarios may impose unacceptable constraints on shielding mass for spacecraft or habitats, tours of duty of crews on Space Station, and on the radius and duration of sorties on planetary surfaces. The NASA Space Radiation Health Program has been devised to develop the knowledge required to accurately predict and to efficiently manage radiation risk. The knowledge will be acquired by means of a peer-reviewed, largely ground-based and investigator-initiated, basic science research program. The NASA Strategic Plan to accomplish these objectives in a manner consistent with the high priority assigned to the protection and health maintenance of crews will be presented.     

Radiation quality and risk estimation in relation to space missions.

While Q is specified as a function of linear energy transfer (LET) in practice the Q for neutrons has been selected by a judgment decision based on the relative biological effectiveness (RBE) to induce stochastic effects. There are no RBE values for tumor induction by heavy ions or protons in humans. Thus, selection of Q values has been based either on LET (or lineal energy) or RBEs from animal experiments. Estimates of Q for heavy ions in low earth orbit (LEO) range from about 5 to 14. The average Q value of all radiation in LEO has been estimated to be about 1.3. There is a lack of experimental data for RBEs for heavy ions but RBE increases as a function of LET. In the case of the Harderian gland the RBE reaches a maximum of 25-30 between about 100-200 keV/micrometer but does not appear to decrease at higher LETs. The International Commission of Radiological Protection have proposed the use of radiation weighting factors in lieu of quality factors. The weighting factors will range from 1 to 20.     

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.     

Combined effects of radiation and trauma.

Injuries, caused by both whole-body irradiation and wounds or burns, have been relatively little studied. Possibly because many investigators think that these injuries are just modified radiation-induced diseases for which the same treatment principles are valid. Other authors had the impression that, for instance, the radiation burn trauma is a new kind of disease which differs significantly from either radiation syndrome alone or from burn disease. There are many experimental data on animals which suggest that the pathology of combined injuries differs significantly from that of radiation-induced disease or of thermal or mechanical traumas. Wounds or burns which, in general, do not cause septicaemia could become entrance ports for bacteria when animals are exposed to whole-body irradiation. Thrombocytopenia is the reason for hemorrhages in wounds. The susceptibility to shock is increased considerably in combined injuries and the formation of callus in the bone fractures is significantly delayed. The healing of wounds and burns in the initial phase of the radiation syndrome does not always differ from healing in the non-irradiated organism. However, a few days or weeks later very serious wound infections and hemorrhages can occur. The additional injuries almost always worsen the development and prognosis of radiation-induced disease. The recommended treatment for combined injuries will differ in many respects from the treatment of wounds and burns or the radiation syndrome.     

Late effects from particulate radiations in primate and rabbit tissues.

Optic tissues in groups of New Zealand white rabbits were irradiated locally at different stages throughout the median life span of the species with a single dose (9 Gy) of 425 MeV/amu Ne ions (LET infinity approximately 30 keV/micrometer) and then inspected routinely for the progression of radiation cataracts. The level of early cataracts was found to be highest in the youngest group of animals irradiated (8 weeks old), but both the onset of late cataracts and loss of vision occurred earlier when animals were irradiated during the second half of the median life span. This age response can have serious implications in terms of space radiation hazards to man. Rhesus monkeys that had been subjected to whole-body skin irradiation (2.8 and 5.6 Gy) by 32 MeV protons (range in tissue approximately 1 cm) some twenty years previously were analysed for radiation damage by the propagation of skin fibroblasts in primary cultures. Such propagation from skin biopsies in MEM-alpha medium (serial cultivation) or in supplemented Ham's F-10 medium (cultivation without dilution) revealed late damage in the stem (precursor) cells of the skins of the animals. The proton fluxes employed in this experiment are representative of those occurring in major solar flares.     

Long-term effects of microgravity and possible countermeasures.

It is well known that long-term exposure to microgravity causes a number of physiological and biochemical changes in humans; among the most significant are: 1) negative calcium balance resulting in the loss of bone; 2) atrophy of antigravity muscles; 3) fluid shifts and decreased plasma volume; and 4) cardiovascular deconditioning that leads to orthostatic intolerance. It is estimated that a mission to Mars may require up to 300 days in a microgravity environment; in the case of an aborted mission, the astronauts may have to remain in reduced gravity for up to three years. Although the Soviet Union has shown that exercise countermeasures appear to be adequate for exposures of up to one year in space, it is questionable whether astronauts could or should have to maintain such regimes for extremely prolonged missions. Therefore, the NASA Life Sciences Division has initiated a program designed to evaluate a number of methods for providing an artificial gravity environment.