Influence of Microgravity on Apoptosis in Cells, Tissues, and Other Systems In Vivo and In Vitro.

All life forms have evolved under the constant force of gravity on Earth and developed ways to counterbalance acceleration load. In space, shear forces, buoyance-driven convection, and hydrostatic pressure are nullified or strongly reduced. When subjected to microgravity in space, the equilibrium between cell architecture and the external force is disturbed, resulting in changes at the cellular and sub-cellular levels (e.g., cytoskeleton, signal transduction, membrane permeability, etc.). Cosmic radiation also poses great health risks to astronauts because it has high linear energy transfer values that evoke complex DNA and other cellular damage. Space environmental conditions have been shown to influence apoptosis in various cell types. Apoptosis has important functions in morphogenesis, organ development, and wound healing. This review provides an overview of microgravity research platforms and apoptosis. The sections summarize the current knowledge of the impact of microgravity and cosmic radiation on cells with respect to apoptosis. Apoptosis-related microgravity experiments conducted with different mammalian model systems are presented. Recent findings in cells of the immune system, cardiovascular system, brain, eyes, cartilage, bone, gastrointestinal tract, liver, and pancreas, as well as cancer cells investigated under real and simulated microgravity conditions, are discussed. This comprehensive review indicates the potential of the space environment in biomedical research.

[Results of study concerning possible influence of rocket space activities on public health].

Using special medical examination results and specified criteria of objective evaluation, the authors summarized results of studies concerning health state of population dwelling in area possibly influenced by rocket space activities factors.

Clinical risk management approach for long-duration space missions.

INTRODUCTION: In the process of crewmember evaluation and certification for long-duration orbital missions, the International Space Station (ISS) Multilateral Space Medicine Board (MSMB) encounters a surprisingly wide spectrum of clinical problems. Some of these conditions are identified within the ISS Medical Standards as requiring special consideration, or as falling outside the consensus Medical Standards promulgated for the ISS program. METHODS: To assess the suitability for long-duration missions on ISS for individuals with medical problems that fall outside of standards or are otherwise of significant concern, the MSMB has developed a risk matrix approach to assess the risks to the individual, the mission, and the program. The goal of this risk assessment is to provide a more objective, evidence- and risk-based approach for aeromedical disposition. Using a 4 x 4 risk matrix, the probability of an event is plotted against the potential impact. Event probability is derived from a detailed review of clinical and aerospace literature, and based on the best available evidence. The event impact (consequences) is assessed and assigned within the matrix. RESULTS: The result has been a refinement of MSMB case assessment based on evidence-based data incorporated into a risk stratification process. This has encouraged an objective assessment of risk and, in some cases, has resulted in recertification of crewmembers with medical conditions which hitherto would likely have been disqualifying. CONCLUSIONS: This paper describes a risk matrix approach developed for MSMB disposition decisions. Such an approach promotes objective, evidence-based decision-making and is broadly applicable within the aerospace medicine community.

Medical qualification of a commercial spaceflight participant: not your average astronaut.

BACKGROUND: Candidates for commercial spaceflight may be older than the typical astronaut and more likely to have medical problems that place them at risk during flight. Since the effects of microgravity on many medical conditions are unknown, physicians have little guidance when evaluating and certifying commercial spaceflight participants. This dynamic new era in space exploration may provide important data for evaluating medical conditions, creating appropriate medical standards, and optimizing treatment alternatives for long-duration spaceflight. CASE: A 57-yr-old spaceflight participant for an ISS mission presented with medical conditions that included moderately severe bullous emphysema, previous spontaneous pneumothorax with talc pleurodesis, a lung parenchymal mass, and ventricular and atrial ectopy. The medical evaluation required for certification was extensive and included medical studies and monitoring conducted in analogue spaceflight environments including altitude chambers, high altitude mixed-gas simulation, zero-G aircraft, and high-G centrifuge. To prevent recurrence of pneumothorax, we performed video-assisted thoracoscopic pleurodesis, and to assess lung masses, several percutaneous or direct biopsies. The candidate's 10-d mission was without incident. CONCLUSION: Non-career astronauts applying for commercial suborbital and orbital spaceflight will, at least in the near future, challenge aerospace physicians with unknowns regarding safety during training and flight, and highlight important ethical and risk-assessment problems. The information obtained from this new group of space travelers will provide important data for the evaluation and in-flight treatment of medical problems that space programs have not yet addressed systematically, and may improve the medical preparedness of exploration-class missions.

Implementation of ALARA radiation protection on the ISS through polyethylene shielding augmentation of the Service Module Crew Quarters.

With 5-7 month long duration missions at 51.6 degrees inclination in Low Earth Orbit, the ionizing radiation levels to which International Space Station (ISS) crewmembers are exposed will be the highest planned occupational exposures in the world. Even with the expectation that regulatory dose limits will not be exceeded during a single tour of duty aboard the ISS, the "as low as reasonably achievable" (ALARA) precept requires that radiological risks be minimized when possible through a dose optimization process. Judicious placement of efficient shielding materials in locations where crewmembers sleep, rest, or work is an important means for implementing ALARA for spaceflight. Polyethylene (CnHn) is a relatively inexpensive, stable, and, with a low atomic number, an effective shielding material that has been certified for use aboard the ISS. Several designs for placement of slabs or walls of polyethylene have been evaluated for radiation exposure reduction in the Crew Quarters (CQ) of the Zvezda (Star) Service Module. Optimization of shield designs relies on accurate characterization of the expected primary and secondary particle environment and modeling of the predicted radiobiological responses of critical organs and tissues. Results of the studies shown herein indicate that 20% or more reduction in equivalent dose to the CQ occupant is achievable. These results suggest that shielding design and risk analysis are necessary measures for reducing long-term radiological risks to ISS inhabitants and for meeting legal ALARA requirements. Verification of shield concepts requires results from specific designs to be compared with onboard dosimetry.

Problems and conception of ensuring radiation safety during Mars missions.

The Mars mission differs from near-Earth manned space flights by radiation environment and duration. The importance of effective using the weight of the spacecraft increases greatly because all the necessary things for the mission must be included in its starting weight. For this reason the development of optimal systems of radiation safety ensuring (RSES) acquires especial importance. It is the result of sharp change of radiation environment in the interplanetary space as compared to the one in the near-Earth orbits and significant increase of the interplanetary flight duration. The demand of a harder limitation of unfavorable factors effects should lead to radiation safety (RS) standards hardening. The main principles of ensuring the RS of the Mars mission (optimizing, radiation risk, ALARA) and the conception of RSES, developed on the basis of the described approach and the experience obtained during orbital flights are presented in the report. The problems that can impede the ensuring of the crew members' RS are also given here.

Radiation protection guidance for activities in low-Earth orbit.

Scientific Committee 75 (SC 75) of the National Council on Radiation Protection and Measurements (NCRP) was assembled for the purpose of providing guidance to NASA concerning radiation protection in low-Earth orbit. The report of SC 75 was published in December 2000 as NCRP Report No. 132. In this presentation an overview of the findings and recommendations of the committee report will be presented.

A comparison of quality factors and weighting factors for characterizing astronaut radiation exposures.

Radiation exposures are typically characterized by two quantities. The first is the absorbed dose, or the energy deposited per unit mass for specific types of radiation passing through specified materials. The same amount of energy deposited in material by two different types of radiation, however, can result in two different levels of risk. Because of this, for the purpose of radiation protection operations, absorbed dose is modified by a second factor intended to normalize the risk associated with a given exposure. We present here an inter-comparison of methods for this modification. First is the radiation quality factor (Q), as defined by ICRP publication 60. This quantity is related functionally to the unrestricted linear energy transfer (LET) of a given radiation, and is multiplied by the absorbed dose to derive the dose equivalent (H). The second method for modifying absorbed dose is the radiation weighting factor, also given in ICRP-60, or as modified in NCRP report 115. To implement the weighting factor, the absorbed dose resulting from incidence of a particular radiation is multiplied by a factor assigned to that type of radiation, giving the equivalent dose. We compare calculations done based on identical fields of radiation representative of that encountered by the MIR space station, applying each of these two methods.

Once we know all the radiobiology we need to know, how can we use it to predict space radiation risks and achieve fame and fortune?

It has been over 40 years since occupational radiation exposures to NASA's astronauts began and more than 300 individuals have been exposed to low and intermediate doses of trapped protons and galactic cosmic rays (GCR). The International Space Station (ISS) will add substantially to this number and significantly increase average lifetime doses. We review these exposures in this report. After many years of investigation, the method used to assess risk have not changed significantly. However, molecular biology and genetics have made enormous progress in establishing the mechanisms of cancer formation, damage to the central nervous system, and individual variation in sensitivity to radiation. We discuss critical questions and possible new approaches to the prediction of risk from space radiation exposures. Experimental models can lead to testable theories that along with extensive biophysical and informatics approaches, will lead to fame and fortune by allowing for accurate projections of astronaut risks and for the development of biological countermeasures.

Space radiation dosimetry in low-Earth orbit and beyond.

Space radiation dosimetry presents one of the greatest challenges in the discipline of radiation protection. This is a result of both the highly complex nature of the radiation fields encountered in low-Earth orbit (LEO) and interplanetary space and of the constraints imposed by spaceflight on instrument design. This paper reviews the sources and composition of the space radiation environment in LEO as well as beyond the Earth's magnetosphere. A review of much of the dosimetric data that have been gathered over the last four decades of human space flight is presented. The different factors affecting the radiation exposures of astronauts and cosmonauts aboard the International Space Station (ISS) are emphasized. Measurements made aboard the Mir Orbital Station have highlighted the importance of both secondary particle production within the structure of spacecraft and the effect of shielding on both crew dose and dose equivalent. Roughly half the dose on ISS is expected to come from trapped protons and half from galactic cosmic rays (GCRs). The dearth of neutron measurements aboard LEO spacecraft and the difficulty inherent in making such measurements have led to large uncertainties in estimates of the neutron contribution to total dose equivalent. Except for a limited number of measurements made aboard the Apollo lunar missions, no crew dosimetry has been conducted beyond the Earth's magnetosphere. At the present time we are forced to rely on model-based estimates of crew dose and dose equivalent when planning for interplanetary missions, such as a mission to Mars. While space crews in LEO are unlikely to exceed the exposure limits recommended by such groups as the NCRP, dose equivalents of the same order as the recommended limits are likely over the course of a human mission to Mars.

Approach and issues relating to shield material design to protect astronauts from space radiation.

One major obstacle to human space exploration is the possible limitations imposed by the adverse effects of long-term exposure to the space environment. Even before human spaceflight began, the potentially brief exposure of astronauts to the very intense random solar energetic particle (SEP) events was of great concern. A new challenge appears in deep space exploration from exposure to the low-intensity heavy-ion flux of the galactic cosmic rays (GCR) since the missions are of long duration and the accumulated exposures can be high. Since aluminum (traditionally used in spacecraft to avoid potential radiation risks) leads to prohibitively expensive mission launch costs, alternative materials need to be explored. An overview of the materials related issues and their impact on human space exploration will be given.

[An analysis of standards documents on the radiation safety problem in space flights and the proposals for their improvement]. / Analiz normativnykh dokumentov po probleme radiatsionnoi bezopasnosti kosmicheskikh poletov i predlozheniia po ikh sovershenstvovaniiu.

The paper considers in retrospective the criteria of radiation hazard during space flight, and approaches to safeguarding the radiation safety to crew members adopted in a sequence of Russian and US standards defining the space radiation limits. Based on comparison of the magnitudes of radiation risk in space flight, total radiation risk over lifetime, the risk of fatal cancer, and risk relation to age, the most meaningful and age-independent criterion has been chosen to set limits and admissible total doses over cosmonaut's career. Justification is given to the range of these doses that still ensures socially acceptable levels of health and performance by the end of space career. Impliable dose limits for critical tissues (blood-forming organs, skin, lenticular epithelium) in consequence of a single acute or continuous exposure for a month, a year or career are discussed.

Space radiation concerns for manned exploration.

Spaceflight exposes astronaut crews to natural ionizing radiation. To date, exposures in manned spaceflight have been well below the career limits recommended to NASA by the National Council of Radiation Protection and Measurements (NCRP). This will not be the case for long-duration exploratory class missions. Additionally. International Space Station (ISS) crews will receive higher doses than earlier flight crews. Uncertainties in our understanding of long-term bioeffects, as well as updated analyses of the Hiroshima. Nagasaki and Chernobyl tumorigenesis data, have prompted the NCRP to recommend further reductions by 30-50% for career dose limit guidelines. Intelligent spacecraft design and material selection can provide a shielding strategy capable of maintaining crew exposures within recommended guidelines. Current studies on newer radioprotectant compounds may find combinations of agents which further diminish the risk of radiation-induced bioeffects to the crew.

[Emphasis of biological research for space radiation].

The paper summarized issues, current status and the recent topics in biological research of space radiation. Researches to estimate a risk associated with space radiation exposure during a long-term manned space flight, such as in the International Space Station, is emphasized because of the large uncertainty of biological effects and a complexity of the radiation environment in space. The Issues addressed are; 1) biological effects and end points in low dose radiation, 2) biological effects under low dose rate and long-term radiation exposure, 3) modification of biological responses to radiation under space environments, 4) various aspects of biological end points vs. cellular and molecular mechanisms, 5) estimation of human risk associated with radiation exposure in space flight, 6) regulations for radiation exposure limits for space workers. The paper also summarized and introduced recent progress in space related radiation researches with various biological systems.

[Measurement and evaluation of radiation dose distribution of gamma-ray altimeter in static test for recovery capsule during simulated landing].

The gamma-ray altimeter, containing a gamma-radioactive source 137Cs with activity of 2.96 x 10(10) Bq, was used to detect the height of the spacecraft recovery capsule during landing. To measure the gamma-dose distribution near to the guidance section, especially at position where the useful load is located in recovery capsule, gamma-dose field at the test-site for one machine test was measured by means of a gamma-dose rate meter FJ-317C and a gamma-dose meter ANRI-01-02. The result showed that the absorbed dose rate at 5 meters from gamma-source on the ground is as low as the radiation protection limit when the altimeter is down to 0.16 m from the ground. The ground reflection effect for gamma-ray decreases as height of the recovery capsule increases. Therefore, the gamma-dose level at useful load in the recovery capsule will meet the requirements of flight safety.

Selection of sterilization methods for planetary return missions.

Two tasks must be accomplished to provide planetary protection for Mars return missions: (1) sterilization of the scientific module to be landed on Mars and (2) reliable sterilization of all material returned to Earth, while ensuring the scientific integrity of martian samples. This paper examines similarity and differences between these two tasks, and includes a discussion of technological implementation conditions and the nature of terrestrial and hypothesized martian microflora. The feasibility of a number of chemical and physical (ultraviolet and ionizing radiation and heating) methods of sterilization for use on the ground and onboard are discussed and compared. A combination of different methods will probably be selected as the most appropriate for ensuring planetary protection on the return mission.

Radiation protection in space.

The challenge for planning radiation protection in space is to estimate the risk of events of low probability after low levels of irradiation. This work has revealed many gaps in our knowledge that require further study. Despite investigations of several irradiated populations, the atomic-bomb survivors remain the primary basis for estimating the risk of ionizing radiation. Compared with previous estimates, two new independent evaluations of available information indicate a significantly greater risk of stochastic effects of radiation (cancer and genetic effects) by about a factor of three for radiation workers, including space travelers. This paper presents a brief historical perspective of the international effort to assure radiation protection in space.

Modern aspects of planetary protection and requirements to sterilization of space hardware.

The viewpoint of working group of Russian experts on the problem of planetary protection for future manned and unmanned Mars mission is presented. Recent data of Martian environment and on survival of terrestrial microorganisms in extreme conditions were used for detailed analysis and overview of planetary protection measures in regard to all possible flight situations including accidental landing. The special emphasis on "Mars-94" mission was done. This analysis resulted in revised formulation of spacecraft sterilization requirements and possible measures for their best implementation. New general combined approach to spacecraft sterilization was proposed. It includes penetrating radiation and heat treatment of spacecraft parts and components which is to be carried out before the final assembly of spacecraft and gaseous radiation sterilization of the whole spacecraft during the flight to Mars (or from Mars for return missions).