Genomic instability and tumorigenic induction in immortalized human bronchial epithelial cells by heavy ions

Carcinogenesis is postulated to be a progressive multistage process characterized by an increase in genomic instability and clonal selection with each mutational event endowing a selective growth advantage. Genomic instability as manifested by the amplification of specific gene fragments is common among tumor and transformed cells. In the present study, immortalized human bronchial (BEP2D) cells were irradiated with graded doses of either 1GeV/nucleon ⁵⁶Fe ions or 150 keV/μm alpha particles. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Tumorigenic cells showed neither ras mutations nor deletion in the p16 tumor suppressor gene. In contrast, they harbored mutations in the p53 gene and over-expressed cyclin D1. Genomic instability among transformed cells at various stage of the carcinogenic process was examined based on frequencies of PALA resistance. Incidence of genomic instability was highest among established tumor cell lines relative to transformed, non-tumorigenic and control cell lines. Treatment of BEP2D cells with a 4 mM dose of the aminothiol WR-1065 significantly reduced their neoplastic transforming response to ⁵⁶Fe particles. This model provides an opportunity to study the cellular and molecular mechanisms involved in malignant transformation of human epithelial cells by heavy ions.     

The biological clock of Neurospora in a microgravity environment.

The circadian rhythm of conidiation in Neurospora crassa is thought to be an endogenously derived circadian oscillation; however, several investigators have suggested that circadian rhythms may, instead, be driven by some geophysical time cue(s). An experiment was conducted on space shuttle flight STS-9 in order to test this hypothesis; during the first 7-8 cycles in space, there were several minor alterations observed in the conidiation rhythm, including an increase in the period of the oscillation, an increase in the variability of the growth rate and a diminished rhythm amplitude, which eventually damped out in 25% of the flight tubes. On day seven of flight, the tubes were exposed to light while their growth fronts were marked. Some aspect of the marking process reinstated a robust rhythm in all the tubes which continued throughout the remainder of the flight. These results from the last 86 hours of flight demonstrated that the rhythm can persist in space. Since the aberrant rhythmicity occurred prior to the marking procedure, but not after, it was hypothesized that the damping on STS-9 may have resulted from the hypergravity pulse of launch. To test this hypothesis, we conducted investigations into the effects of altered gravitational forces on conidiation. Exposure to hypergravity (via centrifugation), simulated microgravity (via the use of a clinostat) and altered orientations (via alterations in the vector of a 1 g force) were used to examine the effects of gravity upon the circadian rhythm of conidiation.     

Studies of vegetation and soils from aerospace measurements

The problem of soil and vegetation recognition with the use of satellite-derived digitized images and sub-satellite spectral brightness measurements at test sites data is discussed. A technique for retrieval of soil humus content is suggested.     

Status of the Hubble Space Telescope observatory

The Hubble Space Telescope activity by NASA and ESA began in 1971 and is now nearing completion. The Scientific Instruments are complete and their performance confirmed. The Optical Telescope Assembly integration is proceeding well, with the crucial Fine Guidance Sensors expected to perform as designed. Telescope delivery to the spacecraft contractor is expected in December 1984. Completion of the Verification and Assembly Program will then be followed by launch in the summer of 1986.     

Plasma convection model and generation of longitudinal currents in the earth's magnetosphere

The aim of this paper is to investigate processes in the magnetosphere and in particular the problems of the interaction of the solar wind with the Earth's magnetic field to produce large-scale convection, electric fields and longitudinal currents in the magnetosphere. The investigation is carried out in the frame of magnetic hydrodynamics. The reason for such an approach can be found in /1/. When calculating the transfer coefficients, the Böhm approximation is used, i.e. it is considered that the plasma in the near-equatorial part of the magnetosphere (quasiplanar geometry is used in the problem for simplification) is sufficiently turbulent that the condition ωτ ≈ 1 is valid (ω is the Larmor frequency of electrons, τ is effective time between two Quasi-collisions). The main subjects of investigation in this paper are the input near the equatorial boundary layer and the plasma layer of the magnetosphere tail.     

Phase separated membrane bioreactor: results from model system studies.

The operation and evaluation of a bioreactor designed for high intensity oxygen transfer in a microgravity environment is described. The reactor itself consists of a zero headspace liquid phase separated from the air supply by a long length of silicone rubber tubing through which the oxygen diffuses in and the carbon dioxide diffuses out. Mass transfer studies show that the oxygen is film diffusion controlled both externally and internally to the tubing and not by diffusion across the tube walls. Methods of upgrading the design to eliminate these resistances are proposed. Cell growth was obtained in the fermenter using Saccharomyces cerevisiae showing that this concept is capable of sustaining cell growth in the terrestrial [correction of terrestial] simulation.     

An empirical model of electron density for low and middle latitudes below 200 km

Our empirical model of electron density (n_e) for quiet and weakly disturbed geomagnetic conditions (Kp not greater 4) takes account of comparative analysis of existing models and of experimental data obtained by rockets and incoherent scatter radar. The model describes the n_e distribution in the 80 to 200 km height range at low and middle latitudes, and to some extent, in the subauroral region. It is presented in analytical form thus allowing one to calculate electron density profiles for any time. The electron density distribution at 140 km depends on the season (day of the year) and on the solar zenith angle. Profile variations during the day are for one season shown. Different from other models, ours specifies the variations during sunrise and sunset and reflects the particular profile shape at night admitting the occurrence of an intermediate layer.     

Soft X-ray characteristics of white dwarfs observed by EXOSAT

EXOSAT has observed 19 hot white dwarfs with alleged strong soft X-ray emission. Positive detection of a large fraction of this sample was obtained, among these practically all hot DA dwarfs. High-resolution spectral data, acquired with the 500 1/mm grating spectrometer, indicates no traces of He in the atmosphere of HZ43, i.e. n(He)/n(H) ? 10^?5 at a photospheric temperature of 60000 K (log g = 8). In contrast, the hot DA1 dwarf Feige 24 shows the presence of an appreciable He-abundance (n(He)/n(H) ? 10^?3); however no simple homogeneously mixed H/He atmosphere can explain the observed spectral shape.     

A new model of the ion composition at 75 to 1000 km for IRI

Ion composition of the ionosphere is an important parameter of any ionospheric model. The International Reference Ionosphere-1979 includes a program for the relative ion composition computation. The program was constructed on the basis of the Danilov and Semenov /1/ empirical model, which averaged 42 rocket measurements of the ion composition at middle latitudes below 200 km, on “AEROS” satellite measurements, and on Taylor's data /2/ above that altitude.     

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.