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Suppression of DNA-PK by RNAi has different quantitative effects on telomere dysfunction and mutagenesis in human lymphoblasts treated with gamma rays or HZE particles.

Basic to virtually all relevant biological effects of ionizing radiation is the underlying damage produced in DNA and the subsequent cellular processing of such damage. The damage can be qualitatively different for different kinds of radiations, and the genetics of the biological systems exposed can greatly affect damage processing and ultimate outcome--the biological effect of concern. The accurate repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genomic integrity and function. Incorrect repair of such lesions results in chromosomal rearrangements and mutations that can lead to cancer and heritable defects in the progeny of irradiated parents. We have focused on the consequent phenotypic effects of faulty repair by examining connections between cellular radiosensitivity phenotypes relevant for carcinogenesis after exposure to ionizing radiation, and deficiencies in various components of the non-homologous end-joining (NHEJ) system. Here we produced deficiencies of individual components of the DNA-dependent protein kinase (DNA-PK) holoenzyme (Ku86 and the catalytic subunit, DNA-PKcs), both singly and in combination, using RNA interference (RNAi) in human lymphoblastoid cell lines. Exposure of cells exhibiting reduced protein expression to either gamma rays or 1 GeV/nucleon iron particles demonstrated differential effects on telomere dysfunction and mutation frequency as well as differential effects between radiation qualities.

Cell Line↗

Visual assessment of the radiation distribution in the ISS Lab module: visualization in the human body.

The US Lab module of the International Space Station (ISS) is a primary working area where the crewmembers are expected to spend majority of their time. Because of the directionality of radiation fields caused by the Earth shadow, trapped radiation pitch angle distribution, and inherent variations in the ISS shielding, a model is needed to account for these local variations in the radiation distribution. We present the calculated radiation dose (rem/yr) values for over 3,000 different points in the working area of the Lab module and estimated radiation dose values for over 25,000 different points in the human body for a given ambient radiation environment. These estimated radiation dose values are presented in a three dimensional animated interactive visualization format. Such interactive animated visualization of the radiation distribution can be generated in near real-time to track changes in the radiation environment during the orbit precession of the ISS.

Computer Simulation↗

[Dynamics of radiation environment of space station "Mir" by the "DOZA-A1" readings].

One of the serious disadvantages of the U.S. (AP-8 and AE-8) and Russian trapped radiation models is the lack of data concerning the dynamics of trapped particles fluences within a time interval shorter than the solar cycle. The available models are capable to predict the energy spectra of trapped particles only for periods in the vicinity of the solar minimum or maximum. The current models are also lacking data about the angular distribution of trapped particles. Meanwhile, these facts are important in conjunction with the problems of radiation safety of space crews. DOZA-A1 incorporating 7 semiconductor detector with a dose sensitivity of 2.4. 10(-4) muGy/pulse and a temporal resolution of 15 seconds, and a reading and charging unit were delivered to MIR in September, 1995; the experiment began in January, 1996. Measurements were made in three locations of the basal module. The articles deals with the analysis and comparison of experimental data with results of other dosimetric determinations and predictions of the trapped radiation models.

Cosmic Radiation↗

Aetiology of acute leukaemia.

Ionising radiation, in high dose and with acute exposure, is a factor that has been implicated in leukaemogenesis, but what is the evidence for leukaemogenesis and exposure to diagnostic X-rays, to natural terrestrial or cosmic ionising radiation, to electromagnetic fields, or to nuclear energy? Why is population mixing and infection a possible explanation for the clusters of childhood acute leukaemias around the nuclear processing plants of Sellafield and Dounreay? These questions, as well as how chemical agents, including therapeutic substances, might contribute to leukaemogenesis, are discussed in this last article in the leukaemia series.

Acute Disease↗

Radiation chemistry of the hippocampal brain slice.

The in vitro hippocampal brain slice is a 0.4 mm thick neural network that can be used to study brain responses to radiation and related injuries. This preparation is unique in that it responds to ionizing radiation within minutes after exposure without complications from changes in vascularity, blood flow, blood pressure, etc. Electrophysiological studies have shown that x- and gamma-rays alter synaptic transmission and spike generation, elements of normal brain activity. To evaluate the role of hydroxyl free radicals (OH) in these changes, slices were exposed to dilute H2O2 solutions. EPR spin trapping experiments verified that OH is produced. Neural responses, while similar, were not identical to those due to radiation, possibly because of a different distribution of OH. Although H2O2 is freely diffusible, it produces OH at specific sites where, e.g. iron reduces it. In contrast, x- and gamma-rays produce OH more uniformly throughout the tissue. H2O2 may provide a better model for high-LET radiation where yields of radical products of water radiolysis are decreased and peroxide reactions predominate.

Cosmic Radiation↗

First flight of the ASTROCULTURE (TM) experiment as a part of the U.S. Shuttle/MIR program.

A number of space-based experiments have been conducted to assess the impact of microgravity on plant growth and development. In general, these experiments did not identify any profound impact of microgravity on plant growth and development, though investigations to study seed development have indicated difficulty in plants completing their reproductive cycle. However, it was not clear whether the lack of seed production was due to gravity effects or some other environmental condition prevailing in the unit used for conducting the experiment. The ASTROCULTURE (TM) flight unit contains a totally enclosed plant chamber in which all the critically important environmental conditions are controlled. Normal wheat (Triticum aestivum L.) growth and development in the ASTROCULTURE (TM) flight unit was observed during a ground experiment conducted prior to the space experiment. Subsequent to the ground experiment, the flight unit was transported to MIR by STS-89, as part of the U.S. Shuttle/MIR program, in an attempt to determine if super dwarf wheat plants that were germinated in microgravity would grow normally and produce seeds. The experiment was initiated on-orbit after the flight unit was transferred from the Space Shuttle to MIR. The ASTROCULTURE (TM) flight unit performed nominally for the first 24 hours after the flight unit was activated, and then the unit stopped functioning abruptly. Since it was not possible to return the unit to nominal operation it was decided to terminate the experiment. On return of the flight unit, it was confirmed that the control computer of the ASTROCULTURE (TM) flight unit sustained a radiation hit that affected the control software embedded in the computer. This experience points out that at high orbital inclinations, such as that of MIR and that projected for the International Space Station, the danger of encountering harmful radiation effects are likely unless the electronic components of the flight hardware are resistant to such impacts.

Agriculture↗

Daily periodicity in the activity of a slide used to perform immunologic reactions at a liquid-solid interface.

Nickel-plated slides were prepared by evaporating a nickel layer (congruent to 4000 A thick) on glass slides in the presence of a magnetic field whose lines of force were perpendicular to the surface of the slides. Such slides are called active. After being coated with a layer of bovine albumin, they could absorb a layer of antibodies 70-80 A thick. However, if the active slides before they were coated with bovine serum albumin, were submitted to a magnetic field with lines of force parallel to the surface, the layer of antibodies absorbed was only 40 A thick. They had become inactive. It has been found that slides remain active at night but that shortly after sunrise they become slowly inactivated and reach a minimum in their activity at exactly the midday period. They regain full activity at sunset. It is shown that the inactivation results from a solar radiation that can be stopped by 3.5 cm of lead. On December 13th, 1974 there was an eclipse of the sun with 65% occultation at noon (Daylight Saving Time). The activity of the slide at noon was 65% of the maximum activity (83 A) observed before sunrise. The thickness of the adsorbed layer of antibodies were 75 A instead of 63 A observed in the absence of the eclipse. The activation of the slides originates in a radiation of non-solar origin that is adsorbed by 1 can of lead.

Animals↗

Effects of dietary supplements on the space radiation-induced reduction in total antioxidant status in CBA mice.

In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by proton, HZE-particle and gamma radiation in CBA mice. The results demonstrated that the plasma level of TAS was significantly decreased (P < 0.05) in CBA mice after exposure to a 50-cGy dose of radiation from HZE particles or a 3-Gy dose of radiation from protons or gamma rays. Diet supplementation with Bowman-Birk Inhibitor Concentrate (BBIC), L-selenomethionine (L-SeM), or a combination of N-acetyl cysteine, sodium ascorbate, co-enzyme Q10 (CoQ10), alpha-lipoic acid, L-SeM and vitamin E succinate could partially or completely prevent the reduction in the plasma level of TAS in CBA mice exposed to proton or HZE-particle radiation. The selected antioxidant combination with or without CoQ10 has a comparable protective effect on the gamma-radiation-induced drop in TAS in CBA mice. These results indicate that BBIC, L-SeM and the selected antioxidant combinations may serve as countermeasures for space radiation-induced adverse biological effects.

Administration, Oral↗

[Space flight effects on bioobjects flown on Cosmos-1514].

The effect of space flight factors, particularly radiation, on Artemia salina cysts, tobacco and rice seeds (embryos and caryopses) was investigated. Artemia salina cysts showed no significant deviations in response to this exposure. Minor changes in certain cyst groups were related to their packing, humidity and preirradiation level. Tobacco seeds exhibited a higher frequency of somatic and morphologic changes that were independent of their packing arrangement. Rice seeds developed no changes that could be associated with space flight effects. The changes seen are considered in relation to the radiation dose absorbed. The results obtained in different space experiments are discussed.

Animals↗

Human exposure to space radiation: role of primary and secondary particles.

Human exposure to space radiation implies two kinds of risk, both stochastic and deterministic. Shielding optimisation therefore represents a crucial goal for long-term missions, especially in deep space. In this context, the use of radiation transport codes coupled with anthropomorphic phantoms allows to simulate typical radiation exposures for astronauts behind different shielding, and to calculate doses to different organs. In this work, the FLUKA Monte Carlo code and two phantoms, a mathematical model and a voxel model, were used, taking the Galactic Cosmic Rays (GCR) spectra from the model of Badhwar and O'Neill. The time integral spectral proton fluence of the August 1972 Solar Particle Event (SPE) was represented by an exponential function. For each aluminium shield thickness, besides total doses the contributions from primary and secondary particles for different organs and tissues were calculated separately. More specifically, organ-averaged absorbed doses, dose equivalents and a form of 'biological dose', defined on the basis of initial (clustered) DNA damage, were calculated. As expected, the SPE doses dramatically decreased with increasing shielding, and doses in internal organs were lower than in skin. The contribution of secondary particles to SPE doses was almost negligible; however it is of note that, at high shielding (10 g cm(-2)), most of the secondaries are neutrons. GCR organ doses remained roughly constant with increasing Al shielding. In contrast to SPE results, for the case of cosmic rays, secondary particles accounted for a significant fraction of the total dose.

Astronauts↗

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.

Aerospace Medicine↗

Radiation measurements aboard NASA ER-2 high altitude aircraft with the Liulin-4J portable spectrometer.

The risks to aircrew health posed by prolonged exposure to low levels of ionizing radiation at aircraft altitudes have recently received renewed attention. Civil and military aircraft currently on the drawing board are expected to operate at higher altitudes (>12 km) and fly longer ranges than do existing aircraft, thereby exposing their crews to higher levels of ionizing radiation, for longer periods of time. We are currently carrying out dosimetric measurements of the ionizing radiation environment at approximately 20 km altitude using portable Si detectors aboard NASA's two ER-2 high altitude research aircraft. The instruments, Liulin-4J, have been extensively calibrated at several particle accelerators. With these instruments, we can measure not only absorbed dose, but also variation of the absorbed dose as a function of time. We report radiation dose measurements as function of time, altitude, and latitude for several ER-2 missions.

Aircraft↗

Biological effects of stellar collapse neutrinos

Massive stars in their final stages of collapse radiate most of their binding energy in the form of MeV neutrinos. The recoil atoms that they produce in elastic scattering off nuclei in organic tissue create radiation damage which is highly effective in the production of irreparable DNA harm, leading to cellular mutation, neoplasia, and oncogenesis. Using a conventional model of the galaxy and of the collapse mechanism, the periodicity of nearby stellar collapses and the radiation dose are calculated. The possible contribution of this process to the paleontological record of mass extinctions is examined.

Animals↗

Risks of radiation cataracts from interplanetary space missions.

Recognition of the human risks from radiation exposure during manned missions in deep space has been fostered by international co-operation; interagency collaboration is facilitating their evaluation. Further co-operation can lead, perhaps by the end of this decade, to an evaluation of one of the three major risks, namely radiation cataractogenesis, sufficient for use in the planning of the manned mission to Mars.

Aluminum↗

A modular solid state detector for measuring high energy heavy ion fragmentation near the beam axis.

A multi-element solid state detector has been designed to measure fluences of fragments produced near the beam axis by high energy heavy ion beams in thick targets. The detector is compact and modular, so as to be readily reconfigured according to the range of fragment charges and energies to be measured. Preamplifier gain settings and detector calibrations are adjustable remotely under computer control. We describe the central detector, its associated detectors and electronics, triggering scheme, data acquisition and particle identification techniques, illustrated by data taken with 600 MeV/u 56Fe beams and thick polyethylene targets at the LBL Bevalac. The applications of this work to space radiation protection are discussed.

Algorithms↗

Radiation risk in manned space flights.

This paper addresses some of the pertinent questions relating to the assessment of radiation risk for humans in space; the paper is not intended as a comprehensive review. The radiation field is briefly summarised and doses to be expected are given based on recent on-board measurements. The problems in adapting terrestrial epidemiological data to the space situation are outlined. Apart from the intrinsic uncertainties in deriving risk factors the specific difficulties are mainly concerned with the effects of energetic charged particles for which no human data exist. The necessity for continuing ground-based research is stressed. Also discussed is whether the principles of radiation protection successfully applied on Earth are really suitable for the space situation or whether they should be replaced by a different approach.

Astronauts↗