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Biomedical subjects

G Gasset

Publications and source records attributed to G Gasset.

At least 19 recordsLinked to original sources

Checkpoint and physiological apoptosis in germ cells proceeds normally in spaceflown Caenorhabditis elegans.

It is important for human life in space to study the effects of environmental factors during spaceflight on a number of physiological phenomena. Apoptosis plays important roles in development and tissue homeostasis in metazoans. In this study, we have analyzed apoptotic activity in germ cells of the nematode C. elegans, following spaceflight. Comparison of the number of cell corpses in wild type or ced-1 mutants, grown under either ground or spaceflight conditions, showed that both pachytene-checkpoint apoptosis and physiological apoptosis in germ cells occurred normally under spaceflight conditions. In addition, the expression levels of the checkpoint and apoptosis related genes are comparable between spaceflight and ground conditions. This is the first report documenting the occurrence of checkpoint apoptosis in the space environment and suggests that metazoans, including humans, would be able to eliminate cells that have failed to repair DNA lesions introduced by cosmic radiation during spaceflight.

Animals↗

Changes in gravitational forces induce modifications of gene expression in A. thaliana seedlings.

By comparing the expression patterns of selected genes from Arabidopsis thaliana (L.) Heynh. grown either at 1 g or on a clinostat (horizontally or vertically inverted, 1 rpm), and either used directly or after hypergravity stimulation, we have shown that the pattern of expression did not proceed in a stereotypical manner. Rather, the selected genes fell into different classes. These classes include (i) those insensitive to the gravitational conditions, (ii) those that are regulated in an opposite manner by hypergravity and clinostat conditions, (iii) those that are desensitised to hypergravity by long-term culture on a clinostat, and (iv) those enhanced by such a treatment. Our data suggest that rapid reorientation of gene expression is likely to occur in response to changes in the gravitational conditions.

Arabidopsis↗

Weightlessness acts on human breast cancer cell line MCF-7.

Because cells are sensitive to mechanical forces, weightlessness might act on stress-dependent cell changes. Human breast cancer cells MCF-7, flown in space in a Photon capsule, were fixed after 1.5, 22 and 48 h in orbit. Cells subjected to weightlessness were compared to 1 g in-flight and ground controls. Post-flight, fluorescent labeling was performed to visualize cell proliferation (Ki-67), three cytoskeleton components and chromatin structure. Confocal microscopy and image analysis were used to quantify cycling cells and mitosis, modifications of the cytokeratin network and chromatin structure. Several main phenomena were observed in weightlessness: The perinuclear cytokeratin network and chromatin structure were looser; More cells were cycling and mitosis was prolonged. Finally, cell proliferation was reduced as a consequence of a cell-cycle blockade; Microtubules were altered in many cells. The results reported in the first point are in agreement with basic predictions of cellular tensegrity. The prolongation of mitosis can be explained by an alteration of microtubules. We discuss here the different mechanisms involved in weightlessness alteration of microtubules: i) alteration of their self-organization by reaction-diffusion processes, and a mathematical model is proposed, ii) activation or deactivation of microtubules stabilizing proteins, acting on both microtubule and microfilament networks in cell cortex.

Actin Cytoskeleton↗

Life span, cancer and non-cancer diseases in mouse exposed to a continuous very low dose of gamma-irradiation.

PURPOSE: To analyse the life-span and pathologies of mice living under a continuous very low-dose gamma-irradiation. MATERIAL AND METHODS: We exposed 300 C57B1/6J female mice, 3 weeks old, to 10 cGy year(-1) gamma-rays while 300 control mice lived in the same room. Irradiation was delivered continuously by thorium nitrate. We kept all the animals until natural death and performed autopsy. RESULTS: No difference was observed in life-span (mean lifespan +/-SE: 805.2 +/- 9.62 days for controls and 815 +/- 9.57 days for irradiated mice), weight curves or food intake. At autopsy, cancer was present in 40.9% of controls and 37.9% of irradiated mice. They were mainly represented by lymphomas (23.7 and 24.9%) and histiocytic sarcomas (12.6 and 8.7%, respectively, for controls and irradiated mice). Vascular diseases occurred in 24.1% of controls and 23% of irradiated mice. Infections were present at autopsy in 14.1 and 12.3%, respectively, of controls and irradiated animals. No statistical difference was observed at the end of the experiment for cancer or non-cancer diseases between the two groups. CONCLUSION: Continuous 10 cGy year(-1) gamma-irradiation had no adverse effect on malignant or non-malignant diseases in this strain of mouse.

Animals↗

Skeletogenesis in sea urchin larvae under modified gravity conditions.

From many points of view, skeletogenesis in sea urchins has been well described. Based on this scientific background and considering practical aspects of sea urchin development (i.e. availability of material, size of larvae, etc.), we wanted to know whether orderly skeletogenesis requires the presence of gravity. The objective has been approached by three experiments successfully performed under genuine microgravity conditions (in the STS-65 IML-2 mission of 1994; in the Photon-10 IBIS mission of 1995 and in the STS-76 S/MM-03 mission of 1996). Larvae of the sea urchin Sphaerechinus granularis were allowed to develop in microgravity conditions for several days from blastula stage onwards (onset of skeletogenesis). At the end of the missions, the recovered skeletal structures were studied with respect to their mineral composition, architecture and size. Live larvae were also recovered for post-flight culture. The results obtained clearly show that the process of mineralisation is independent of gravity: that is, the skeletogenic cells differentiate correctly in microgravity. However, abnormal skeleton architectures were encountered, particularly in the IML-2 mission, indicating that the process of positioning of the skeletogenic cells may be affected, directly or indirectly, by environmental factors, including gravity. Larvae exposed to microgravity from blastula to prism/early pluteus stage for about 2 weeks (IBIS mission), developed on the ground over the next 2 months into normal metamorphosing individuals.

Animals↗

The sea urchin larva, a suitable model for biomineralisation studies in space (IML-2 ESA Biorack experiment '24-F urchin').

By the ESA Biorack 'F-24 urchin' experiment of the IML-2 mission, for the first time the biomineralisation process in developing sea urchin larvae could be studied under real microgravity conditions. The main objectives were to determine whether in microgravity the process of skeleton formation does occur correctly compared to normal gravity conditions and whether larvae with differentiated skeletons do 'de-mineralise'. These objectives have been essentially achieved. Postflight studies on the recovered 'sub-normal' skeletons focused on qualitative, statistical and quantitative aspects. Clear evidence is obtained that the basic biomineralisation process does actually occur normally in microgravity. No significant differences are observed between flight and ground samples. The sub-normal skeleton architectures indicate, however, that the process of positioning of the skeletogenic cells (determining primarily shape and size of the skeleton) is particularly sensitive to modifications of environmental factors, potentially including gravity. The anatomical heterogeneity of the recovered skeletons, interpreted as long term effect of an accidental thermal shock during artificial egg fertilisation (break of climatisation at LSSF), masks possible effects of microgravity. No pronounced demineralisation appears to occur in microgravity; the magnesium component of the skeleton seems yet less stable than the calcium. On the basis of these results, a continuation of biomineralisation studies in space, with the sea urchin larva as model system, appears well justified and desirable.

Animals↗

Influence of the environment in space on the biochemical characteristics of human low density lipoproteins.

The purpose of this experiment was to study the efficiency of protective substances on the effects of cosmic radiation in space on low density lipoproteins. This environment induced modifications in LDL consisting of an increase of lipid peroxidation markers (hydroperoxides, thiobarbituric acid reactive substances). In contrast, apo B was not affected by cosmic radiation as shown by the stability of the trinitrobenzenesulfonic acid reactivity and the tryptophan content. Furthermore, oxidation of LDL was partially inhibited by the addition of cysteamine or/and probucol before the spaceflight experiment. The hydroperoxide formation was almost completely inhibited by cysteamine. It was concluded that antioxidants can exert a protective effect against peroxidative stress induced by the space environment.

Cosmic Radiation↗

Influence of a long duration exposure, 69 months, to the space flight factors in Artemia cysts, tobacco and rice seeds.

Three french laboratories have participated in the Free Flyer Biostack experiment. Artemia cysts, tobacco seeds and rice caryopsis and embryos were used. Biological objects in monolayers were dead. In opposite, a large fraction of samples used in bulk survived. A stimulatory effect occurred in the first steps of development in Artemia cysts. In fact, the larval survival was unchanged or slightly reduced. In tobacco a drastic decrease in germination and survival rate was observed. Space flight did not induce genetic changes. In rice, results depend on the variety which was investigated; the growth rate stimulation in flight samples is discussed with respect to controls.

Animals↗

Growth and division of Escherichia coli under microgravity conditions.

The growth rate in glucose minimal medium and time of entry into the stationary phase in pepton cultures were determined during the STS 42 mission of the space shuttle Discovery. Cells were cultured in plastic bags and growth was stopped at six different time points by lowering the temperature to 5 degrees C, and at a single time point, by formaldehyde fixation. Based on cell number determination, the doubling time calculated for the flight samples of glucose cells was shorter (46 min) than for the ground samples (59 min). However, a larger cell size expected for more rapidly growing cells was not observed by volume measurements with the electronic particle counter, nor by electron microscopic measurement of cell dimensions. Only for cells fixed in flight was a larger cell length and percentage of constricted cells found. An optical density increase in the peptone cultures showed an earlier entry into the stationary phase in flight samples, but this could not be confirmed by viability counts. The single sample with cells fixed in flight showed properties indicative of growth stimulation. However, taking all observations together, we conclude that microgravity has no effect on the growth rate of exponentially growing Escherichia coli cells.

Cell Division↗

Behavior of bacteria and antibiotics under space conditions.

We have previously reported an increase of the "resistance" to antibiotics of bacteria during space missions. In the present experiment, we studied the growth of Escherichia coli cultured in vitro in space in the presence of dihydrostreptomycin: tritiated and nontritiated. This experiment was carried out during the STS 42 mission aboard the U.S. Space Shuttle Discovery (IML-1 program). Cells were cultured in plastic bags and growth was stopped at six different time points by lowering the temperature to 5 degrees C. Several methods were used: viable cell counting by Colony Forming Units; total cell number by optical densitometry; electron microscopy; radioactivity measurements. The investigations show no difference between flight and ground experiments for the cultures without antibiotic. The growth rate with antibiotic was accelerated in flight, the growth yield was not changed, and there were no differences in the ultrastructures. The results suggest some changes in antibiotic binding in space. We did not observe any differences between the cultures developed in flight in the 1-g centrifuge and the cultures placed in the static rack in microgravity.

Colony Count, Microbial↗

[Effects of hypergravity on Paramecium tetraurelia].

Previous space experiments carried out in Paramecium tetraurelia have shown that exposure to microgravity results in an enhancement of cell multiplication. An opposite effect occurs when paramecia are exposed to hypergravity. Changes in cell growth rate observed in hypergravity cannot be ascribed to the bacteria present in the culture medium, the same effect being observed when paramecia grow in sterile medium.

Animals↗

Theoretical and experimental investigations on the fast rotating clinostat.

We have investigated both theoretically and experimentally the validity of the fast rotating clinostat to simulate microgravity for a free swimming single-cell organism such as the paramecium. Computer simulations show that cells on suspension move as cells cultivated in space. However, rotated paramecia are still affected by gravity, as shown by the variations in the rate of paramecium rotation on their axis. Using a fast clinostat, which allows to investigate simultaneously twenty cultures, we have observed a stimulating effect on cell growth rate similar to that previously reported in space. All these results point towards the fact that the fast clinostat can reproduce some of the effects of microgravity on paramecia.

Animals↗

Influence of low-temperature storage and glucose starvation on growth recovery in Escherichia coli relA and relA+ strains.

To study the influence of microgravity on bacterial growth behavior during a space mission, the special experimental conditions and the hardware environment necessitate storage of cells at low temperature, and permit a relatively short experimental period. Before this experimental period, cells have to recover their condition of steady-state growth, because it is only in this condition that the growth behavior of the flight and ground populations can be adequately compared. To meet these requirements and to obtain cells which recover rapidly their steady-state growth, we analyzed the size and shape of Escherichia coli cells during storage at 4 degrees C, with and without previous glucose starvation of the cells. It appeared that cells stored at low temperature in the presence of glucose continued to increase in average mass and assumed ovoid shapes. In addition, upon restoration of maximal growth rate at 37 degrees C, they continued to increase in size and showed a transient overshoot of their final steady-state value, which was reached after about 5 h. Cells previously starved for glucose, however, maintained their average size and rod-shape during low-temperature storage. Recovery of the starved cells was most rapid in the relA+ strain which, contrary to the isogenic relA strain, showed no overshoot and reached its final steady-state size within 2 h.

Cold Temperature↗

Investigations of the effects of cosmic rays on Artemia cysts and tobacco seeds; results of Exobloc II experiment, flown aboard Biocosmos 1887.

Artemia (Brine shrimp) cysts and tobacco seeds, dormant biological material devoid of metabolic activity, were flown aboard the Soviet Biocosmos 1887 in order to investigate the effects of cosmic rays. Artemia cysts and tobacco seeds were used in bulk or in monolayers sandwiched with track detectors. Biological and physical units were located outside and inside the spacecraft. Stacks included lead shielding in order to expose the objects to different doses of radiation. Total dosimetry was performed using thermoluminescent detectors. In spite of low levels of doses, the space flight resulted in a decrease in developmental capacity of Artemia cysts, and in a higher mutation rate in tobacco seeds. The more obvious responses occurred, in both cases, in biological objects exposed to the highest doses. These results are compared to those of previous space experiments.

Animals↗

Effects of angular speed in responses of Paramecium tetraurelia to hypergravity.

The paper shows the results of investigations carried out in a single cell organism. Paramecium tetraurelia exposed to different gravitational levels. Hypergravity resulted in a decrease in cell growth rate. The responses depend on g level and angular speed of the centrifuge; furthermore they depend also on small short fluctuations in g levels, delta g, due to the swimming of the cells inside the culture tubes. Delta g depends on angular speed and size of the holding device. The inhibitory effect of hypergravity, for the same angular speed, increases with respect of the diameter of the culture tubes.

Animals↗

Space environmental factors affecting responses to radiation at the cellular level.

Previous space experiments suggest a high value for the RBE of cosmic radiation. A possible explanation could be a change in cell radiosensitivity due to a combined effect of radiation and other factors related to the space environment and to the space flight. Results of the EXOBLOC II experiment support this assumption. On earth, vibrations or accelerations applied before or after irradiation can change the responses to radiation. Microgravity could be the main factor affecting the radiosensitivity and DNA repair but this hypothesis must be confirmed by additional experiments.

Animals↗