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PubMed2001

A biophysical model for estimating the frequency of radiation-induced mutations resulting from chromosomal translocations.

Gene mutations can be induced by radiation as a result of chromosomal translocations. A biophysical model is developed to estimate the frequency of this type of mutation induced by low-LET radiation. Mutations resulting from translocations are assumed to be formed by misrejoining of two DNA double strand breaks (DSB), one within the gene and one on a different chromosome. The chromosome containing the gene is assumed to occupy a spherical territory and does not overlap spatially with other chromosomes. Misrejoining between two DSB can occur only if the two DSB are closer than an interaction distance at the time of their induction. Applying the model to mutations of the hprt gene induced in G0 human lymphocyte cells by low-LET radiation, it is calculated that mutations resulting from translocations account for about 14% of the total mutations. The value of the interaction distance is determined to be 0.6 micrometers by comparing with the observed frequency of translocations in the X-chromosome.

Cesium Radioisotopes↗
PubMed2002

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↗
PubMed2002

Solar particle event organ doses and dose equivalents for interplanetary crews: variations due to body size.

Proper assessments of spacecraft shielding requirements and concomitant estimates of risk to critical body organs of spacecraft crews from energetic space radiation require accurate, quantitative methods of characterizing the compositional changes in these radiation fields as they pass through the spacecraft and overlying tissue. When estimating astronaut radiation organ doses and dose equivalents it is customary to use the Computerized Anatomical Man (CAM) model of human geometry to account for body self-shielding. Usually, the distribution for the 50th percentile man (175 cm height; 70 kg mass) is used. Most male members of the U.S. astronaut corps are taller and nearly all have heights that deviate from the 175 cm mean. In this work, estimates of critical organ doses and dose equivalents for interplanetary crews exposed to an event similar to the October 1989 solar particle event are presented for male body sizes that vary from the 5th to the 95th percentiles. Overall the results suggest that calculations of organ dose and dose equivalent may vary by as much as approximately 15% as body size is varied from the 5th to the 95th percentile in the population used to derive the CAM model data.

Aluminum↗
PubMed2002

Probability of cell hits in selected organs and tissues by high-LET particles at the ISS orbit.

The fluence of high-LET particles (HLP) with LET infinity H2O greater than 15 keV micrometers-1 in selected organs and tissues were measured with plastic nuclear track detectors using a life-size human phantom on the 9th Shuttle-Mir Mission (STS-91). The planar-track fluence of HLP during the 9.8-day mission ranged from 1.9 x 10(3) n cm-2 (bladder) to 5.1 x 10(3) n cm-2 (brain) by a factor of 2.7. Based on these data, a probability of HLP hits to a matured cell of each organ or tissue was roughly estimated for a 90-day ISS mission. In the calculation, all cells were assumed to be spheres with a geometric cross-sectional area of 500 micrometers2 and the cell-hit frequency from isotropic space radiation can be described by the Poisson-distribution function. As results, the probability of one or more than 1 hit to a single cell by HLP for 90 days ranged from 17% to 38%; that of two or more than 2 hits was estimated to be 1.3-8.2%.

Brain↗
PubMed2003

In vivo and in vitro measurements of complex-type chromosomal exchanges induced by heavy ions.

Heavy ions are more efficient in producing complex-type chromosome exchanges than sparsely ionizing radiation, and this can potentially be used as a biomarker of radiation quality. We measured the induction of complex-type chromosomal aberrations in human peripheral blood lymphocytes exposed in vitro to accelerated H-, He-, C-, Ar-, Fe- and Au-ions in the LET range of approximately 0.4-1400 keV/micrometers. Chromosomes were analyzed either at the first post-irradiation mitosis, or in interphase, following premature condensation by phosphatase inhibitors. Selected chromosomes were then visualized after FISH-painting. The dose-response curve for the induction of complex-type exchanges by heavy ions was linear in the dose-range 0.2-1.5 Gy, while gamma-rays did not produce a significant increase in the yield of complex rearrangements in this dose range. The yield of complex aberrations after 1 Gy of heavy ions increased up to an LET around 100 keV/micrometers, and then declined at higher LET values. When mitotic cells were analyzed, the frequency of complex rearrangements after 1 Gy was about 10 times higher for Ar- or Fe- ions (the most effective ions, with LET around 100 keV/micrometers) than for 250 MeV protons, and values were about 35 times higher in prematurely condensed chromosomes. These results suggest that complex rearrangements may be detected in astronauts' blood lymphocytes after long-term space flight, because crews are exposed to HZE particles from galactic cosmic radiation. However, in a cytogenetic study of ten astronauts after long-term missions on the Mir or International Space Station, we found a very low frequency of complex rearrangements, and a significant post-flight increase was detected in only one out of the ten crewmembers. It appears that the use of complex-type exchanges as biomarker of radiation quality in vivo after low-dose chronic exposure in mixed radiation fields is hampered by statistical uncertainties.

Biomarkers↗
PubMed2003

Low fluence.

The question of the appropriate extrapolation to low dose has long been a subject of controversy. A linear no-threshold model is favored by regulatory bodies as the basis of RBE assignments and estimates of radiation hazards to the general population. This model is largely supported by extensive application of the linear-quadratic survival formula "fitted" statistically to a wide variety of experimental data obtained at doses typically exceeding 1 Gy, and then extrapolated to mGy for practical applications, and even to the prediction of hazards from single electrons. Such extrapolations are questionable at best, and may even prove hazardous for risk evaluations. Fluence and geometry rather than dose based data are proposed as a basis for a limiting "threshold" for a "low dose" extrapolation. The proposed threshold is one where the fluence of particles is one per square micron, where on average only 2/3 of the 1 micrometers2 pixels covering an irradiated area are traversed by one or more particles. The corresponding dose threshold is determined by the LET of the bombarding radiation. For relativistic electrons this dose is about 0.032 Gy.

Cell Physiological Phenomena↗
PubMed2003

M-FISH analysis of chromosome aberrations in human fibroblasts exposed to energetic iron ions in vitro.

Confluent human fibroblast cells were exposed to 6 Gy gamma-rays or 200 MeV/nucleon Fe ions at 0.7 or 3 Gy. The cells were allowed to repair for 24 hours after exposure and chromosomes were collected using a premature chromosome condensation technique with calyculin-A. Chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allows identification of both complex and truly incomplete exchanges. Results showed that both doses of the Fe ions produced higher ratios of complex to simple exchanges and lower ratio of complete to incomplete exchanges than the 6 Gy gamma-exposure. The ratios of aberration yields were similar for the two doses of Fe ions. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, indicating this is the maximum number of chromosome domains traversed by a single Fe ion track.

Cell Line↗
PubMed2003

Materials trade study for lunar/gateway missions.

The National Aeronautics and Space Administration (NASA) administrator has identified protection from radiation hazards as one of the two biggest problems of the agency with respect to human deep space missions. The intensity and strength of cosmic radiation in deep space makes this a 'must solve' problem for space missions. The Moon and two Earth-Moon Lagrange points near Moon are being proposed as hubs for deep space missions. The focus of this study is to identify approaches to protecting astronauts and habitats from adverse effects from space radiation both for single missions and multiple missions for career astronauts to these destinations. As the great cost of added radiation shielding is a potential limiting factor in deep space missions, reduction of mass, without compromising safety, is of paramount importance. The choice of material and selection of the crew profile play major roles in design and mission operations. Material trade studies in shield design over multi-segmented missions involving multiple work and living areas in the transport and duty phase of space mission's to two Earth-Moon co-linear Lagrange points (L1) between Earth and the Moon and (L2) on back side of the moon as seen from Earth, and to the Moon have been studied. It is found that, for single missions, current state-of-the-art knowledge of material provides adequate shielding. On the other hand, the choice of shield material is absolutely critical for career astronauts and revolutionary materials need to be developed for these missions. This study also provides a guide to the effectiveness of multifunctional materials in preparation for more detailed geometry studies in progress.

Astronauts↗
PubMed1997

Photosynthesis and respiration of a wheat stand at reduced atmospheric pressure and reduced oxygen.

A 34-day functional test was conducted in Johnson Space Center's Variable Pressure Growth Chamber (VPGC) to determine responses of a wheat stand to reduced pressure (70 kPa) and modified partial pressures of carbon dioxide and oxygen. Reduced pressure episodes were generally six to seven hours in duration, were conducted at reduced ppO2 (14.7 kPa), and were interrupted with longer durations of ambient pressure (101 kPa). Daily measurements of stand net photosynthesis (Pn) and dark respiration (DR) were made at both pressures using a ppCO2 of 121 Pa. Corrections derived from leakage tests were applied to reduced pressure measurements. Rates of Pn at reduced pressure averaged over the complete test were 14.6% higher than at ambient pressure, but rates of DR were unaffected. Further reductions in ppO2 were achieved with a molecular sieve and were used to determine if Pn was enhanced by lowered O2 or by lowered pressure. Decreased ppO2 resulted in enhanced rates of Pn, regardless of pressure, but the actual response was dependent on the ratio of ppO2/ppCO2. Over the range of ppO2/ppCO2 of 80 to 200, the rate of Pn declined linearly. Rate of DR was unaffected over the same range and by dissolved O2 levels down to 3.1 ppm, suggesting that normal rhizosphere and canopy respiration occur at atmospheric ppO2 levels as low as 11 kPa. Partial separation of effects attributable to oxygen and those related to reduced pressure (e.g. enhanced diffusion of CO2) was achieved from analysis of a CO2 drawdown experiment. Results will be used for design and implementation of studies involving complete crop growth tests at reduced pressure.

Atmospheric Pressure↗
PubMed1997

Atmospheric leakage and method for measurement of gas exchange rates of a crop stand at reduced pressure.

The variable pressure growth chamber (VPGC) was used in a 34-day functional test to grow a wheat crop using reduced pressure (70 kPa) episodes totalling 131 hours. Primary goals of the test were to verify facility and subsystem performance at 70 kPa and to determine responses of a wheat stand to reduced pressure and modified partial pressures of carbon dioxide and oxygen. Operation and maintenance of the chamber at 70 kpa involved continuous evacuation of the chamber atmosphere, leading to CO2 influx and efflux. A model for calculating CO2-exchange rates (net photosynthesis and dark respiration) was developed and tested and involved measurements of chamber leakage to determine appropriate corrections. Measurement of chamber leakage was based on the rate of pressure change over a small pressure increment (70.3 to 72.3 kPa) with the pump disabled. Leakage values were used to correct decreases and increases in chamber CO2 concentration resulting from net photosynthesis (Ps) and dark respiration (DR), respectively. Composite leakage corrections (influx and efflux) at day 7 of the test were 9% and 19% of the changes measured for Ps and DR, respectively. On day 33, composite corrections were only 3% for Ps and 4% for DR. During the test, the chamber became progressively tighter; the leak rate at 70.3 kPa decreasing from 2.36 chamber volumes/day pretest, to 1.71 volumes/day at the beginning of the test, and 1.16 volumes/day at the end of the test. Verification of the short-term leakage tests (rate of pressure rise) were made by testing CO2 leakage with the vacuum pump enabled and disabled. Results demonstrate the suitability of the VPGC or conducting gas exhange measurements of a crop stand at reduced pressure.

Air Conditioning↗
PubMed1998

Radiation measurements on the flight of IML-2.

The second flight of the International Microgravity Laboratory (IML-2) on Space Shuttle flight STS-65 provided a unique opportunity for the intercomparison of a wide variety of radiation measurement techniques. Although this was not a coordinated or planned campaign, by sheer chance, a number of space radiation experiments from several countries were flown on this mission. There were active radiation measuring instruments from Japan and US, and passive detectors from US, Russia, Japan, and Germany. These detectors were distributed throughout the Space Shuttle volume: payload bay, middeck, flight deck, and Spacelab. STS-65 was launched on July 8, 1994, in a 28.45 degrees x 306 km orbit for a duration of 14 d 17 hr and 55 min. The crew doses varied from 0.935 mGy to 1.235 mGy. A factor of two variation was observed between various passive detectors mounted inside the habitable Shuttle volume. There is reasonable agreement between the galactic cosmic ray dose, dose equivalent and LET spectra measured by the tissue equivalent proportional counter flown in the payload bay with model calculations. There are significant differences in the measurements of LET spectra measured by different groups. The neutron spectrum in the 1-20 MeV region was measured. Using fluence-dose conversion factors, the neutron dose and dose equivalent rates were 11 +/- 2.7 microGy/day and 95 +/- 23.5 microSv/day respectively. The average east-west asymmetry of trapped proton (>3OMeV) and (>60 MeV) dose rate was 3.3 and 1.9 respectively.

Cosmic Radiation↗
PubMed1998

Radiation environment on the Mir orbital station during solar minimum.

The Mir station has been in a 51.65 degrees inclination orbit since March 1986. In March 1995, the first US astronaut flew on the Mir-18 mission and returned on the Space Shuttle in July 1995. Since then three additional US astronauts have stayed on orbit for up to 6 months. Since the return of the first US astronaut, both the Spektr and Priroda modules have docked with Mir station, altering the mass shielding distribution. Radiation measurements, including the direct comparison of US and Russian absorbed dose rates in the Base Block of the Mir station, were made during the Mir-18 and -19 missions. There is a significant variation of dose rates across the core module; the six locations sampled showed a variation of a factor of nearly two. A tissue equivalent proportional counter (TEPC) measured a total absorbed dose rate of 300 microGy/day, roughly equally divided between the rate due to trapped protons from the South Atlantic Anomaly (SAA) and galactic cosmic radiation (GCR). This dose rate is about a factor of two lower than the rate measured by the thinly shielded (0.5 g cm-2 of Al) operational ion chamber (R-16), and about 3/2 of the rate of the more heavily shielded (3.5 g cm-2 of Al) ion chamber. This is due to the differences in the mass shielding properties at the location of these detectors. A comparison of integral linear energy transfer (LET) spectra measured by TEPC and plastic nuclear track detectors (PNTDs) deployed side by side are in remarkable agreement in the LET region of 15-1000 keV/micrometer, where the PNTDs are fully efficient. The average quality factor, using the ICRP-26 definition, was 2.6, which is higher than normally used. There is excellent agreement between the measured GCR dose rate and model calculations, but this is not true for trapped protons. The measured Mir-18 crew skin dose equivalent rate was 1133 microSv/day. Using the skin dose rate and anatomical models, we have estimated the blood-forming organ (BFO) dose rate and the maximum stay time in orbit for International Space Station crew members.

Atlantic Ocean↗
PubMed1998

Microsatellite instability in human mammary epithelial cells transformed by heavy ions.

We analyzed DNA and proteins obtained from normal and transformed human mammary epithelial cells for studying the neoplastic transformation by high-LET irradiation in vitro. We also examined microsatellite instability in human mammary cells transformed to various stages of carcinogenesis, such as normal, growth variant and tumorigenic, using microsatellite marker D5S177 on the chromosome 5 and CYl7 on the Chromosome 10. Microsatellite instabilities were detected in the tumorigenic stage. These results suggest that microsatellite instability may play a role in the progression of tumorigenecity. The cause of the genomic instability has been suggested as abnormalities of DNA-repair systems which may be due to one of the three reasons: 1) alterations of cell cycle regulating genes. 2) mutations in any of the DNA mismatch repair genes, 3) mutation in any of the DNA strand breaks repair genes. No abnormality of these genes and encoded proteins, however was found in the present studies. These studies thus suggest that the microsatellite instability is induced by an alternative mechanism.

Breast↗
PubMed2000

Oncogenic transformation of mammalian cells by ultrasoft X-rays and alpha particles.

For a better understanding of oncogenic cell transformation by ionizing radiation, we conducted experiments with ultrasoft X rays and low energy alpha particles. Confluent C3H10T1/2 cells were irradiated by Al-K (1.5 keV) X rays or alpha particles from plutonium through a thin mylar sheet, on which the cells attached and grew. Our results indicated that Al-K X rays were more effective in causing cell inactivation and oncogenic transformation than 60Co gamma rays but less effective than 1.0 and 3.7 MeV alpha particles. There was no significant difference between 1.0 and 3.7 MeV alpha particles in transforming cells although the latter were slightly more effective than the former in producing lethal effect. These results indicated that track structure is important in causing biological effects by ionizing radiation.

Alpha Particles↗
PubMed2002

Human otolith-ocular reflexes during off-vertical axis rotation: effect of frequency on tilt-translation ambiguity and motion sickness.

The purpose of this study was to examine how the modulation of tilt and translation otolith-ocular responses during constant velocity off-vertical axis rotation varies as a function of stimulus frequency. Eighteen human subjects were rotated in darkness about their longitudinal axis 30 degrees off-vertical at stimulus frequencies between 0.05 and 0.8 Hz. The modulation of torsion decreased while the modulation of horizontal slow phase velocity (SPV) increased with increasing frequency. It is inferred that the ambiguity of otolith afferent information is greatest in the frequency region where tilt (torsion) and translational (horizontal SPV) otolith-ocular responses crossover. It is postulated that the previously demonstrated peak in motion sickness susceptibility during linear accelerations around 0.3 Hz is the result of frequency segregation of ambiguous otolith information being inadequate to distinguish between tilt and translation.

Adult↗
PubMed2000

Cerebral vasoconstriction precedes orthostatic intolerance after parabolic flight.

The effects of brief but repeated bouts of micro- and hypergravity on cerebrovascular responses to head-up tilt (HUT) were examined in 13 individuals after (compared to before) parabolic flight. Middle cerebral artery mean flow velocity (MCA MFV; transcranial Doppler ultrasound), eye level blood pressure (BP) and end tidal CO(2) (P(ET)CO(2)) were measured while supine and during 80 degrees HUT for 30 min or until presyncope. In the postflight tests subjects were classified as being orthostatically tolerant (OT) (n = 7) or intolerant (OI) (n = 6). BP was diminished with HUT in the OT group in both tests (p < 0.05) whereas postflight BP was not different from supine in the OI group. Postflight compared to preflight, the reduction in P(ET)CO(2) with HUT (p < 0.05) increased in both groups, although significantly so only in the OI group (p < 0.05). The OI group also had a significant decrease in supine MCA MFV postflight (p < 0.05) that was unaccompanied by a change in supine P(ET)CO(2). The decrease in MCA MFV that occurred during HUT in both groups preflight (p < 0.05) was accentuated only in the OI group postflight, particularly during the final 30 s of HUT (p < 0.05). However, this accentuated decrease in MCA MFV was not correlated to the greater decrease in P(ET)CO(2) during the same period (R = 0.20, p = 0.42). Although cerebral vascular resistance (CVR) also increased in the OI group during the last 30 s of HUT postflight (p < 0.05), the dynamic autoregulatory gain was not simultaneously changed. Therefore, we conclude that in the OI individuals, parabolic flight was associated with cerebral hypoperfusion following a paradoxical augmentation of CVR by a mechanism that was not related to changes in autoregulation nor strictly to changes in P(ET)CO(2).

Adult↗
PubMed1998

Motion sickness and development of synergy within the spatial orientation system. A hypothetical unifying concept.

Adaptation to research paradigms such as rotating rooms and optical alteration of visual feedback during movement results in development of perceptual-motor programs that provide the reflexive assistance that is necessary to skilled control of movement and balance. The discomfort and stomach awareness that occur during the adaptation process has been attributed to conflicting sensory information about the state of motion. Vestibular signals depend on the kinematics of head movements irrespective of the presence or absence of signals from other senses. We propose that sensory conflict when vestibular signals are at least one component of the conflict are innately disturbing and unpleasant. This innate reaction is part of a continuum that operates early in life to prevent development of inefficient perceptual-motor programs. This reaction operates irrespective of and in addition to reward and punishment from parental guidance or goal attainment to yield efficient control of whole body movement in the operating environment of the individual. The same mechanism is involved in adapting the spatial orientation system to strange environments. This conceptual model "explains" why motion sickness is associated with adaptation to novel environments and is in general consistent with motion sickness literature.

Adaptation, Physiological↗
PubMed1998

Relationship between selected orientation rest frame, circular vection and space motion sickness.

Space motion sickness (SMS) and spatial orientation and motion perception disturbances occur in 70-80% of astronauts. People select "rest frames" to create the subjective sense of spatial orientation. In microgravity, the astronaut's rest frame may be based on visual scene polarity cues and on the internal head and body z axis (vertical body axis). The data reported here address the following question: Can an astronaut's orientation rest frame be related and described by other variables including circular vection response latencies and space motion sickness? The astronaut's microgravity spatial orientation rest frames were determined from inflight and postflight verbal reports. Circular vection responses were elicited by rotating a virtual room continuously at 35 degrees/s in pitch, roll and yaw with respect to the astronaut. Latency to the onset of vection was recorded from the time the crew member opened their eyes to the onset of vection. The astronauts who used visual cues exhibited significantly shorter vection latencies than those who used internal z axis cues. A negative binomial regression model was used to represent the observed total SMS symptom scores for each subject for each flight day. Orientation reference type had a significant effect, resulting in an estimated three-fold increase in the expected motion sickness score on flight day 1 for astronauts who used visual cues. The results demonstrate meaningful classification of astronauts' rest frames and their relationships to sensitivity to circular vection and SMS. Thus, it may be possible to use vection latencies to predict SMS severity and duration.

Adult↗