SAMBO-GEOS: On three-dimensional substorm dynamics — A case study for 4 March 1979

For investigations of the isolated magnetospheric substorm the ground-based and satellite geophysical data are discussed. The active phase of the substorm has two parts: an active-convective phase and a classical active phase. The analysed data show that the breakup of the substorm takes place at closed and not very much stretched magnetic field lines.     

Neoplastic cell transformation by high-LET radiation: molecular mechanisms.

Experimental data on molecular mechanisms are essential for understanding the bioeffects of radiation and for developing biophysical models, which can help in determining the shape of dose-response curves at very low doses, e.g., doses less than 1 cGy. Although it has been shown that ionizing radiation can cause neoplastic cell transformation directly, that high-LET heavy ions in general can be more effective than photons in transforming cells, and that the radiogenic cell transformation is a multi-step process [correction of processes], we know very little about the molecular nature of lesions important for cell transformation, the relationship between lethal and transformational damages, and the evolution of initial damages into final chromosomal aberrations which alter the growth control of cells. Using cultured mouse embryo cells (C3H10T1/2) as a model system, we have collected quantitative data on dose-response curves for heavy ions with various charges and energies. An analysis of these quantitative data suggested that two DNA breaks formed within 80 angstroms may cause cell transformation and that two DNA breaks formed within 20 angstroms may be lethal. Through studies with restriction enzymes which produce DNA damages at specific sites, we have found that DNA double strand breaks, including both blunt- and cohesive-ended breaks, can cause cell transformation in vitro. These results indicate that DNA double strand breaks can be important primary lesions for radiogenic cell transformation and that blunt-ended double strand breaks can form lethal as well as transformational damages due to misrepair or incomplete repair in the cell. The RBE-LET relationship is similar for HGPRT gene mutation, chromosomal deletion, and cell transformation, suggesting common lesions may be involved in these radiation effects. The high RBE of high-LET radiation for cell killing and neoplastic cell transformation is most likely related to its effectiveness in producing DNA double strand breaks in mammalian cells. At present the role of oncogenes in radiation cell transformation is unclear.     

Neoplastic transformation of hamster embryo cells by heavy ions

We have studied the induction of morphological transformation of Syrian hamster embryo cells by low doses of heavy ions with different linear energy transfer (LET), ranging from 13 to 400 keV/μm. Exponentially growing cells were irradiated with ¹²C or ²⁸Si ion beams generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC), inoculated to culture dishes, and transformed colonies were identified when the cells were densely stacked and showed a crisscross pattern. Over the LET range examined, the frequency of transformation induced by the heavy ions increased sharply at very low doses no greater than 5 cGy. The relative biological effectiveness (RBE) of the heavy ions relative to 250 kVp X-rays showed an initial increase with LET, reaching a maximum value of about 7 at 100 keV/μm, and then decreased with the further increase in LET. Thus, we confirmed that high LET heavy ions are significantly more effective than X-rays for the induction of in vitro cell transformation.     

Repair of DNA double-strand breaks and cell killing by charged particles.

It has been suggested that it is not simple double-strand breaks (dsb) but the non-reparable breaks which correlate well with the high biological effectiveness of high LET radiations for cell killing (Kelland et al., 1988; Radford, 1986). We have compared the effects of charged particles on cell death in 3 pairs of cell lines which are normal or defective in the repair of DNA dsbs. For the cell lines SL3-147, M10, and SX10 which are deficient in DNA dsb repair, RBE values were close to unity for cell killing induced by charged particles with linear energy transfer (LET) up to 200 keV/micrometer and were even smaller than unity for the LET region greater than 300 keV/micrometer. The inactivation cross section (ICS) increased with LET for all 3 pairs. The ICS of dsb repair deficient mutants was always larger than that of their parents for all the LET ranges, but with increasing LET the difference in ICS between the mutant and its parent became smaller. Since a small difference in ICS remained at LET of about 300 keV/micrometer, dsb repair may still take place at this high LET, even if its role is apparently small. These results suggest that the DNA repair system does not play a major role in protection against the attack of high LET radiations and that a main muse of cell death is non-reparable dsb which are produced at a higher yield compared with low LET radiations. No correlation was observed between DNA content or nuclear area and ICS.     

Maps of hydrogen isotopes at low altitudes in the inner zone from sampex observations

The PET instrument aboard the SAMPEX satellite has provided us with long-term intra-calibrated observations of geomagnetically trapped protons and deuterons in the inner zone, suitable for use in constraining the low-altitude portions of radiation belt models being developed as successors to AP-8. These observations have been summarized elsewhere (Looper et al., 1996). Here we report a detection of geomagnetically-trapped tritium at energies from 14 to 35 MeV/nuc below L = 1.2, at about 1/8 the flux of deuterium previously reported at that location and at similar energy per nucleon. We also demonstrate the utility of the SAMPEX/PET observations for measuring the east-west anisotropy in the trapped particle flux at low altitudes, which is due to displacement of particle gyrocenters from the position of observation in a region of strong flux gradients. This anisotropy is implicitly ignored in omnidirectional radiation-flux models, but it can be important to mission planners considering how to distribute shielding over the surface of oriented spacecraft in low Earth orbit.     

Effect of track structure and radioprotectors on the induction of oncogenic transformation in murine fibroblasts by heavy ions

The oncogenic potential of high-energy ⁵⁶Fe particles (1 GeV/nucleon) accelerated with the Alternating Gradient Synchrotron at the Brookhaven National Laboratory was examined utilizing the mouse C3H 10T1/2 cell model. The dose-averaged LET for high-energy ⁵⁶Fe is estimated to be 143 keV/μm with the exposure conditions used in this study. For ⁵⁶Fe ions, the maximum relative biological effectiveness (RBE_max) values for cell survival and oncogenic transformation were 7.71 and 16.5 respectively. Compared to 150 keV/μm ⁴He nuclei, high-energy ⁵⁶Fe nuclei were significantly less effective in cell killing and oncogenic induction. The prostaglandin E₁ analog misoprostol, an effective oncoprotector of C3H 10T1/2 cells exposed to X rays, was evaluated for its potential as a radioprotector of oncogenic transformation with high-energy ⁵⁶Fe. Exposure of cells to misoprostol did not alter ⁵⁶Fe cytotoxicity or the rate of ⁵⁶Fe-induced oncogenic transformation.     

Tissue responses to low protracted doses of high LET radiations or photons: early and late damage relevant to radio-protective countermeasures.

Early and late murine tissue responses to single or fractionated low doses of heavy charged particles, fission-spectrum neutrons or gamma rays are considered. Damage to the hematopoietic system is emphasized, but results on acute lethality, host response to challenge with transplanted leukemia cells and life-shortening are presented. Low dose rates per fraction were used in some neutron experiments. Split-dose lethality studies (LD 50/30) with fission neutrons indicated greater accumulation of injury during a 9 fraction course (over 17 days) than was the case for gamma-radiation. When total doses of 96 or 247 cGy of neutrons or gamma rays were given as a single dose or in 9 fractions, a significant sparing effect on femur CFU-S depression was observed for both radiation qualities during the first 11 days, but there was not an earlier return to normal with dose fractionation. During the 9 fraction sequence, a significant sparing effect of low dose rate on CFU-S depression was observed in both neutron and gamma-irradiated mice. CFU-S content at the end of the fractionation sequence did not correlate with measured LD 50/30. Sustained depression of femur and spleen CFU-S and a significant thrombocytopenia were observed when a total neutron dose of 240 cGy was given in 72 fractions over 24 weeks at low dose rates. The temporal aspects of CFU-S repopulation were different after a single versus fractionated neutron doses. The sustained reduction in the size of the CFU-S population was accompanied by an increase in the fraction in DNA synthesis. The proliferation characteristics and effects of age were different for radial CFU-S population closely associated with bone, compared with the axial population that can be readily aspirated from the femur. In aged irradiated animals, the CFU-S proliferation/redistribution response to typhoid vaccine showed both an age and radiation effect. After high single doses of neutrons or gamma rays, a significant age- and radiation-related deficiency in host defense mechanisms was detected by a shorter mean survival time following challenge with transplantable leukemia cells. Comparison of dose-response curves for life shortening after irradiation with fission-spectrum neutrons or high energy silicon particles indicated high initial slopes for both radiation qualities at low doses, but for higher doses of silicon, the effect per Gy decreased to a value similar to that for gamma rays. The two component life-shortening curve for silicon particles has implications for the potential efficacy of radioprotectants. Recent studies on protection against early and late effects by aminothiols, prostaglandins, and other compounds are discussed.     

Biological UV dosimeters in simulated space conditions.

Polycrystalline uracil thin layers participate in the phage and uracil response (PUR) experiment, assigned to the biological dosimetry of the extraterrestrial solar radiation on the International Space Station (ISS). In ground based experiments (experiment verification tests), the following space parameters were simulated and studied: temperature, vacuum and short wavelength UV (UV-C, down to 200 nm) radiation. The closed uracil samples proved to be vacuum-tight for 7 days. In the tested temperature range (from -20 to +40 degrees C) the uracil samples are stable. The kinetic of dimer formation (dimerization) and reversion (monomerization) of uracil dimers due to short wavelength UV radiation was detected, the monomerization efficiency of the polychromatic deuterium lamp is higher than that of the germicidal lamp. A mathematical model describing the kinetic of monomerization-dimerization was constructed. Under the influence of UV radiation the dimerization-monomerization reactions occur simultaneously, thus the additivity law of the effect of the various wavelengths is not applicable.     

The MELISSA pilot plant facility as as integration test-bed for advanced life support systems.

The different advances in the Micro Ecological Life Support System Alternative project (MELISSA), fostered and coordinated by the European Space Agency, as well as in other associated technologies, are integrated and demonstrated in the MELISSA Pilot Plant laboratory. During the first period of operation, the definition of the different compartments at an individual basis has been achieved, and the complete facility is being re-designed to face a new period of integration of all these compartments. The final objective is to demonstrate the potentiality of biological systems such as MELISSA as life support systems. The facility will also serve as a test bed to study the robustness and stability of the continuous operation of a complex biological system. This includes testing of the associated instrumentation and control for a safe operation, characterization of the chemical and microbial safety of the system, as well as tracking the genetic stability of the microbial strains used. The new period is envisaged as a contribution to the further development of more complete biological life support systems for long-term manned missions, that should be better defined from the knowledge to be gained from this integration phase. This contribution summarizes the current status of the Pilot Plant and the planned steps for the new period.