Chromosome aberrations in the blood lymphocytes of astronauts after space flight.

Cytogenetic analysis of the lymphocytes of astronauts provides a direct measurement of space radiation damage in vivo, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. Chromosome exchanges were measured in the blood lymphocytes of eight crew members after their respective space missions, using fluorescence in situ hybridization (FISH) with chromosome painting probes. Significant increases in aberrations were observed after the long-duration missions. The in vivo dose was derived from the frequencies of translocations and total exchanges using calibration curves determined before flight, and the RBE was estimated by comparison with individually measured physical absorbed doses. The values for average RBE were compared to the average quality factor (Q) from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. The ratio of aberrations identified as complex was slightly higher after flight, which is thought to be an indication of exposure to high-LET radiation. To determine whether the frequency of complex aberrations measured in metaphase spreads after exposure to high-LET radiation was influenced by a cell cycle delay, chromosome damage was analyzed in prematurely condensed chromosome samples collected from two crew members before and after a short-duration mission. The frequency of complex exchanges after flight was higher in prematurely condensed chromosomes than in metaphase cells for one crew member.     

Bone biochemistry in rat femoral diaphysis after space flight

The aim of this experiment was to identify the location of the biochemical changes associated with depressed mineralization during space flight. We carried out biochemical analysis of 4 sections of the femoral diaphyses from 107 day old male rats flown aboard Cosmos 2044 Biosatellite for 16 days. Control femurs were preflight, vivarium, synchronous for feed, cage and temperature exposure, and a flight simulation model. Distal sections in both the flight and synchronous femurs showed mineral deficits associated with reduced levels of the reducible cross-link product of type I collagen, dehydro-dihydroxylysinonorleucine (deH-DHLNL) (p<.05). Unloaded bones in the ground based flight simulation model showed changes in cross-links similar to flight and synchronous controls, but were not associated with the mineral deficit. Mean values of elements measured in each section of all groups revealed significant associations (p<.005) between the non-collagenous protein, osteocalcin and calcium (r=0.774), phosphorus (r=-.624) and deH-DHLNL/deH-HLNL (r=.883). The ratio of the nonreducible cross-link, pyridinoline, to its lysl analogue, deoxypyridinoline, was consistently lower in the distal than proximal sections of the groups tested. None of the changes during space flight were unique to flight bone. The most significant and extensive changes in bone composition, i.e. mineral deficits associated with changes in both osteocalcin and reducible cross-links, were located in the distal section of the diaphysis of the femur.     

Behavioral and functional vestibular disorders after space flight: I. Mammals

The review presents data on functional disorders in mammals caused by changes in the vestibular system after space flight. These data show that the mammalian vestibular system responds to weightlessness dissimilarly at different ontogenetic stages. During the embryonic period, orbital space flight conditions have a little effect on the developing vestibular system and even promote normal fetal development. During the early postnatal period, when optimal sensorymotor tactics arise, long-term exposure to space flight conditions leads to the development of novel, “extraterrestrial”, sensory-motor programs that may fixate in CNS for life. In adult individuals, substantial vestibular changes and disorders may occur immediately after landing depending on the weightlessness duration. An adult organism has to solve two concurrent and mutually conflicting problems: to adapt to weightlessness and not to adapt to it in order to facilitate readaptation after return. Thus, individuals have to counteract weightlessness to retain a maximum of their pre-flight health status. The means of such a counteraction have to be adjusted according to the weightlessness duration. It is noteworthy, however, that not all functional changes occurring in adult individuals under weightlessness can be adequately accounted for. Some of them can assume a chronic or even pathological character. The review raises for the first time the question of necessity to include into the scope of studies the effect of weightlessness on a senile (senescent) organism and its vestibular system. We believe that development of space gerontology as a special branch of space biology and medicine is undoubtedly of interest and may become practically important in the future in view of the ever-growing age of space explorers.     

Ultrastructure of skeletal muscle fibers in monkeys after space flight

It is known that exposure of humans and animals to microgravity causes reduction in the cross-sected area of muscle fibers and muscle atrophy. These changes also involve ultrastructural alterations in muscle fibers. Therefore primates, that are physiologically close to humans, are to be examined to help a better understanding of the nature of these ultrastructural changes is muscles and muscle fibers. Although failed to find any relevant published data on the quantitative aspects of ultrastructural changes in muscle fibers of space-flown primates we believe that it is important to examine these aspects. The postflight study of monkey's m. soleus, and m. vastus lateralis did not reveal any significant changes in volume density of the myofibrillar apparatus. Mitochondria of m. soleus showed a distinct reduction in volume density, being more obvious in the subsarcolemmal zone than in the central one. Mitochondria of m. vastus lateralis showed a decrease (P > 0.05) in volume density. Following the flight, m. soleus and m. vastus lateralis of the monkeys showed a significant increase in the mean area of myofibrils, and a trend towards a decrease in the number of myofibrils per 100 micron 2. Besides, m. soleus showed a significant increase in the mean area of mitochondria, and a trend towards a decrease in the number of mitochondria per 100 micron 2. In m. vastus lateralis of the monkeys after space flight the number opf mitochondria tended to decrease and the mean area showed differential changes. It can be postulated that these phenomena may be associated with a reduction in the diffusion surface of mitochondria resulting from the diminished myofibrillar volume.     

Ultrastructural changes in somatosensory cortex of albino rats during space flight

For the first time, mammalian brain has been studied during space flight aboard NASA orbital laboratory Spacelab-2. The main ultrastructural differences in the somatosensory cortex of the brain fixed under microgravity conditions and after landing include an increased number of degenerating presynaptic axon terminals after landing. Apparently, this is due to a sharp increase in afferent impulsation in the cortex during and after landing.     

Mutations induced in Drosophila during space flight.

To examine the possible effects of space radiation on living organisms, fruit flies Drosophila melanogaster were loaded on the US Space Shuttle Endeavour, and after the flight we have analyzed two types of mutations, sex-linked recessive lethal mutations induced in male reproductive cells and somatic mutations which give rise to morphological changes in hairs growing on the surface of wing epidermal cells. Wild type strains and a radiation-sensitive strain mei-41 were used. The frequencies of sex-linked recessive lethal mutations in flight groups were 2 and 3 times higher for wild type Canton-S and mei-41 strains, respectively, than those in ground control groups. By contrast, the frequencies of wing-hair somatic mutations differed little between flight and control groups. The possibility that the space environment causes mutations in certain types of cells such as male reproductive cells, is discussed.     

Antigen-specific lymphocyte proliferative responses in inbred mice after Trichinella spiralis infection.

The in vitro antigen-specific lymphoproliferative response of spleen, mesenteric lymph node (MLN), and coeliac lymph node (CLN) cells taken from various strains of inbred mice infected with Trichinella spiralis was assessed. In most experiments cell populations were stimulated with excretory/secretory antigens (ESA) derived from adult and larval worms. Lymphoid cells collected 5-7 days postinfection were usually the most responsive to ESA as measured by [3H]thymidine uptake. Spleen cells were more responsive than either MLN or CLN cells. There was a correlation between in vitro ESA stimulation and worm rejection in strong- and weak-responder strains of mice. Spleen and MLN cells of NFS mice showed higher antigen-specific responsiveness, whereas the same cells from B10.BR (H-2k) and B10.Q (H-2q) strains of mice were less responsive. Among intermediate responder strains 2 patterns were observed. Spleen and MLN cells of BuB and DBA/1 mice responded more strongly than those of C3H mice. Dose-response experiments demonstrated that increasing the infective dose of larvae to the host usually increased subsequent in vitro antigen-specific lymphoproliferation. Furthermore, non-MHC-linked genes appear to be the primary determinant of antigen-specific T-cell-proliferative responses in inbred mice infected with T. spiralis.     

Effect of microgravity on plasma catecholamine responses to stressors during space flight

The effect of microgravity on the sympathicoadrenal system (SAS) activity in humans and animals has not yet been clarified. Our previous studies suggested that the SAS activity, evaluated by circulating and/or urinary catecholamine (CA) levels in astronauts during space flights, was found to be rather unchanged. However, CA levels were measured in astronauts only at rest conditions. The aim of the present study was to investigate effect of microgravity during space flight and post-flight readaptation on responsiveness of the SAS to somatic and psychic stressors evaluated by levels of catecholamines and their metabolite in the blood of the Slovak cosmonaut during his stay on board the space station Mir.     

Artificial gravity in space flight

Clearly, physiologic adaptation to terrestrial life for all animals is assured only by frequent encounters with gravity. Indeed, upon exposure to weightlessness in space flight, losses of physiologic functions quickly begin. Some physiologic parameters change more rapidly than others, but the deconditioning process starts rapidly. The rates of functional losses for all affected parameters are interesting in that they appear to approach a limit; i.e., losses of these functions may not continue until indefinitely. The regulation of this functional asymptotic response to space is not known, but probably based on functional requirements of the body to life itself and perhaps genetic expression. The latter controlling mechanism (DNA) functions only on aquatic (weightless) animals on Earth--land animals must stimulate these physiologic functions as they relate to gravity on a regular frequent basis. This loss of regulation upon entering the weightless environment is fascinating since land-based animals including the humans have evolved from millions (perhaps billions) of years of terrestrially adapted ancestors. One would expect some DNA involvement in the regulation of its physiology, but it appears to be absent. Therefore, if the functional debilitation of space is to be denied, we must begin to understand the adaptation process of the sole basis for the control of our physiologic processes on land; i.e., how gravity regulates our biologic functions. To learn about this regulatory mechanism, some inquiry into how aquatic animals first adapted to living on land might be helpful.     

Changes in structure and metabolism in the m. vastus lateralis in monkeys after a space flight

Monkeys developed a significant reduction in size of the m. vastus lateralis' fast and slow fibres, the amount of protein in them remaining the same.     

Oxidative phosphorylation in rat skeletal muscles after space flight on board biosatellites

Polarographic analysis of biological oxidation in rat's skeletal muscles after the 18- and 22-day flights revealed changes specific for the flight animals: oxidative phosphorylation uncoupling, distinct inertness of energy accumulation after 10 hrs of landing. Tissue respiration's inhibition was observed in both flight and synchronous rats suggesting the effect of other than microgravity factors. Energy metabolism in muscles of flight animals returned to the pre-flight level later (29 d) compared to the synchronous rats (6 d). Muscles of different functions (predominance of fast or slow fibers) showed similar responses of energy metabolism to weightlessness, i.e. inhibition of the intensity and decline of the energy efficiency of oxidative processes. A decrease in dehydrogenase activity has been found in the first day of recovery. The effects may be caused by the inhibition of both aerobic and anaerobic metabolism after space flight.     

Recombination in Drosophila in space flight

An experiment with Drosophila melanogaster males was performed aboard the Artificial Satellite "Kosmos-1667". Mutagenic effects of a 7-day space flight on intergene recombination in chromosome 2 were studied. The space flight factors decreased the frequency of recombination. A model experiment on a laboratory centrifuge demonstrated insignificant increase in recombination frequency caused by acceleration.     

Skeletal responses to space flight and the bed rest analog: a review

The potential for loss of bone mineral mass due to space flight was recognized by space scientists even before man's first venture into micro-gravity. Early life science studies in both the U.S. and Russian space programs attempted to measure the effects of reduced gravity on skeletal homeostasis, and these measurements have become more sophisticated with time. Bone-related measurements have typically included: bone mineral density measured by X-ray absorptiometry and more recently CT scanning; bonerelated hormones and other biochemical markers of bone turnover; and calcium excretion and balance. These measurements, conducted over the last 4 decades, have shed light on the nature of disuse bone loss and have provided preliminary information regarding bone recovery. Ground-based analog (bed rest) studies have provided information complementary to the space flight data and have allowed the testing of various countermeasures to bone loss. In spite of the wealth of knowledge obtained thus far, many questions remain regarding bone loss, bone recovery, and the factors affecting these skeletal processes. This paper will summarize the skeletal data obtained to date by the U.S. and Russian space programs and in ground-based disuse studies. In addition, related body composition data will be briefly discussed, as will possible countermeasures to space flight-induced bone loss.     

Bone mineral and lean tissue loss after long duration space flight

The loss of bone and muscle is a major concern for long duration space flight. In December of 1989, we established a collaboration with Russian colleagues to determine the bone and lean tissue changes in cosmonauts before and after flights on the Mir space station lasting 4-14.4 months. Eighteen crew members received a lumbar spine and hip DEXA scan (Hologic 1000W) before and after flight; 17 crew members received an additional whole body scan. All results were expressed as percent change from baseline per month of flight in order to account for the different flight times. The pre-and post-flight data were analyzed using Hotelling's T(2) for 3 groups of variables: spine, neck of femur, trochanter; whole body BMD and subregions; lean (total, legs, arms) and fat (total only). A paired t-test was used as a follow-up to the Hotelling's T(2) to identify the individual measurements that were significantly different. These data define the rate and extent of bone and lean tissue loss during long duration space flight and indicate that the current in-flight exercise program is not sufficient to completely ameliorate bone and muscle loss during weightlessness.     

Antibodies to muscle fiber antigens in the cosmonauts after a space flight]

The study of serum samples, obtained from 15 cosmonauts before and after space flights, with the use of the indirect fluorescent method showed that in 7 cosmonauts antibodies to different elements of the human heart muscle appeared after flights. Strong and very strong luminescence of the elements of heart muscle tissue was detected in the cosmonauts after the third space flight. When studying the sera on sections of bovine heart muscle tissue, the reactions of the sera taken before and after flights were found to have no essential differences.     

Slide staining device for use during space flight.

A slide staining device is described that performs Gram and Wright stains during space flight. Reagents and liquid wastes are contained within a closed system.