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At least 19 records

Dose protraction studies with low- and high-LET radiations on neoplastic cell transformation in vitro

The effects of the low- and high-LET radiation (by X-rays, Co-60, and heavy ions) on the transformation of neoplastic cells were studied using cultured C3H10T1/2 mouse embryo cells. The transformed colonies in the confluent cell monolayers were recognized as focuses composed of highly polar fibroblastic multilayered criss-cross arrays of densely stained cells. For the low-LET radiation, there was a decrease in cell killing and cell transformation frequency when cells were irradiated with fractionated doses and at a low dose rate, indicating that cultured mammalian cells can repair both subtransformation and potential transformation lesions. No sparing effect, however, was found for the high-LET radiation. An enhancement of cell transformation was observed for low-dose/rate argon (400 MeV/u; 120 keV/micron) and iron particles (600 MeV/u; 200 keV/micron). The molecular mechanism for this enhancement effect is not known.

Yang, Tracy Chui-Hsu↗

Chromosomal changes in cultured human epithelial cells transformed by low- and high-LET radiation

For a better assessment of radiation risk in space, an understanding of the responses of human cells, especially the epithelial cells, to low- and high-LET radiation is essential. In our laboratory, we have successfully developed techniques to study the neoplastic transformation of two human epithelial cell systems by ionizing radiation. These cell systems are human mammary epithelial cells (H184B5) and human epidermal keratinocytes (HEK). Both cell lines are immortal, anchorage dependent for growth, and nontumorigenic in athymic nude mice. Neoplastic transformation was achieved by irradiating cells successively. Our results showed that radiogenic cell transformation is a multistep process and that a single exposure of ionizing radiation can cause only one step of transformation. It requires, therefore, multihits to make human epithelial cells fully tumorigenic. Using a simple karyotyping method, we did chromosome analysis with cells cloned at various stages of transformation. We found no consistent large terminal deletion of chromosomes in radiation-induced transformants. Some changes of total number of chromosomes, however, were observed in the transformed cells. These transformants provide an unique opportunity for further genetic studies at a molecular level.

NASA Discipline Number 04-10↗

Neoplastic cell transformation by high-LET radiation - Molecular mechanisms

Quantitative data were collected on dose-response curves of cultured mouse-embryo cells (C3H10T1/2) irradiated with heavy ions of various charges and energies. Results suggests that two breaks formed on DNA within 80 A may cause cell transformation and that two DNA breaks formed within 20 A may be lethal. From results of experiments with restriction enzymes which produce DNA damages at specific sites, it was found that DNA double strand breaks are 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 for high-LET radiation is similar to that for HGPRT locus mutation, chromosomal deletion, and cell transformation, indicating that common lesions may be involved in these radiation effects.

Yang, Tracy Chui-Hsu↗

Cataractogenesis from high-LET radiation and the Casarett model

The long-term effects on specific animal tissues of exposure to heavy ion irradiation are studied in experiments on cataractogenesis in mice and rabbits. Five groups of rabbits at ages from 8 weeks to 5.3 years were irradiated to a dose of 9.0 Gy of Bragg plateau Ne-20 ions, while mice were exposed to single and total fractionated doses of 4.17 Gy gamma rays or 0.40 to 1.20 Gy of C-12, Ne-20 or Ar-40 particles. Measurements of lens opacities over time show that in the year since irradiation, cataractogenesis is delayed and less severe in rabbits irradiated at age 6 months compared to younger animals, although it is possible that the late effects in adults will surpass those found in the young. The fractionation of the total dose of gamma rays in mice is observed to lead to a marked reduction in the extent of lens opacity after one year, while fractionated heavy ion doses caused a greater degree of posterior lens opacification. Evaluations of the effects of the LET of different ions on cataractogenesis are consistent with RBEs of about 5, 3 and 1-2 for Ar-40, Ne-20 and C-12 ions, respectively. Results thus support the Casarett model of radiation damaging stem cell populations that are not necessarily part of the vasculature.

Cox, A. B.↗

Radiation protection issues in galactic cosmic ray risk assessment

Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.

NASA Program Radiation Health↗

Implications of the new radiation exposure limits on Space Station Freedom crews

Levels of acceptable risk of radiation exposure for SSF crews have been studied. Since the cancer risk per dose equivalent has increased over the last decade, new dose-equivalent limits have been recommended. An astronaut may not receive more than a depth-dose equivalent of 50 rem/year. It is found that a 180-day stay aboard Freedom could result in a worst case depth-dose of 30 rem, and a 180-day mission in a nominally shielded spacecraft in a constant atmospheric density orbit with a varying altitude could result in a depth-dose equivalent of 10 rem. This is twice the annual allowable dose-equivalent for terrestrial radiation workers. It is noted that the present understanding of the biological effectiveness of high-LET radiation is not adequate for accurate health risk assessments and that further research is necessary.

Stanford, M.↗

DNA-DSB in CHO-K1 cells induced by heavy-ions: Break rejoining and residual damage (GSI)

DNA double strand breaks (DSB's) are the critical lesions involved in cellular effects of ionizing radiation. Therefore, the evaluation of DSB induction in mammalian cells after heavy ion irradiation is an essential task for the assessment of high-LET radiation risk in space. Of particular interest has been the question of how the biological efficiency for the cellular inactivation endpoint relates to the initial lesions (DSBs) at varying LETs. For cell killing, an increased Relative Biological Efficiency (RBE) has been determined for highLET radiation around 100-200 keV/mu m. At higher LET, the RBE's decrease again to values below one for the very heavy particles. At GSI, DSB-induction was measured in CHO-K1 cells following irradiation with accelerated particles covering a wide LET range. The electrophoretic elution of fragmented DNA out of agarose plugs in a constant electrical field was applied for the detection of DSB's. The fraction of DNA retained was determined considering the relative intensities of ethidium bromide fluorescence in the well and in the gel lane. Dose-effect curves were established, from which the RBE for DSB induction was calculated at a fraction of 0.7 of DNA retained In summary, these rejoining studies are in line with an enhanced severity of the DNA DSB's at higher LET's, resulting in a decreased repairability of the induced lesions. However, no information concerning the fidelity of strand breaks rejoining is provided in these studies. To assess correct rejoining of DNA fragments an experimental system involving individual DNA hybridization bands has been set up. In preliminary experiments Sal I generated DNA fragments of 0.9 Mbp were irradiated with xrays and incubated for repair However, restitution of the original signals was not observed, probably due to the high radiation dose necessary for breakage of a fragment of this size. A banding pattern with NotI hybridization signals in a higher MW range (3Mbp) has been obtained by varying the electrophoretic conditions and correct rejoining studies will be further developed in this system.

Taucher-Scholz, G.↗

Accelerated heavy particles and the lens. VII: The cataractogenic potential of 450 MeV/amu iron ions

PURPOSE. To determine the cataractogenic potential dose of high velocity iron ions as a fixation of dose administered singly or fractionated. The dose is critical to risk assessment and to theories of radiation action and cataractogenesis. METHODS. Twenty-eight-day-old rats were examined by slit-lamp biomicroscopy on a weekly-bi-weekly basis for more than 2 yr after radiation exposure. For the acute exposure study doses of 1, 2, 5, 25, and 50 cGy were evaluated. The fractionated regimens involved total doses of 2, 25, and 50 cGy. The reference radiation consisted of 50, 100, 200, or 700 cGy of 250 kilovolt (peak) x-rays. RESULTS. In accordance with previous findings in the rat using 570 MeV/amu 40Ar ions, the relative biologic effectiveness increased rapidly with decreasing dose, reaching values as high as 100. Unlike 40Ar ions, fractionation of the 56Fe doses did not produce a consistent enhancement at any of the doses examined. CONCLUSIONS. The data support the previous findings of a high cataractogenic potential for high linear energy transfer (LET) radiation. The effectiveness for the production of cataracts increases with decreasing dose relative to x-rays and is independent of dose protraction. Although the present study did not reveal a consistent enhancement of effect when the ions were applied in fractions, the results are consistent with at least one theory of the inverse dose-rate effect observed for high-LET radiation.

NASA Discipline Number 04-10↗

Radiological health risks to astronauts from space activities and medical procedures

Radiation protection standards for space activities differ substantially from those applied to terrestrial working situations. The levels of radiation and subsequent hazards to which space workers are exposed are quite unlike anything found on Earth. The new more highly refined system of risk management involves assessing the risk to each space worker from all sources of radiation (occupational and non-occupational) at the organ level. The risk coefficients were applied to previous space and medical exposures (diagnostic x ray and nuclear medicine procedures) in order to estimate the radiation-induced lifetime cancer incidence and mortality risk. At present, the risk from medical procedures when compared to space activities is 14 times higher for cancer incidence and 13 times higher for cancer mortality; however, this will change as the per capita dose during Space Station Freedom and interplanetary missions increases and more is known about the risks from exposure to high-LET radiation.

Peterson, Leif E.↗

Potential health effects of space radiation

Crewmembers on missions to the Moon or Mars will be exposed to radiation belts, galactic cosmic rays, and possibly solar particle events. The potential health hazards due to these space radiations must be considered carefully to ensure the success of space exploration. Because there is no human radioepidemiological data for acute and late effects of high-LET (Linear-Energy-Transfer) radiation, the biological risks of energetic charged particles have to be estimated from experimental results on animals and cultured cells. Experimental data obtained to date indicate that charged particle radiation can be much more effective than photons in causing chromosome aberrations, cell killing, mutation, and tumor induction. The relative biological effectiveness (RBE) varies with biological endpoints and depends on the LET of heavy ions. Most lesions induced by low-LET radiation can be repaired in mammalian cells. Energetic heavy ions, however, can produce large complex DNA damages, which may lead to large deletions and are irreparable. For high-LET radiation, therefore, there are less or no dose rate effects. Physical shielding may not be effective in minimizing the biological effects on energetic heavy ions, since fragments of the primary particles can be effective in causing biological effects. At present the uncertainty of biological effects of heavy particles is still very large. With further understanding of the biological effects of space radiation, the career doses can be kept at acceptable levels so that the space radiation environment need not be a barrier to the exploitation of the promise of space.

Yang, Chui-Hsu↗

Effects of radiation upon the light-sensing elements of the retina as characterized by scanning electron microscopy

A model system using Necturus maculosus, the common mudpuppy, was established for evaluating effects of radiation upon the light-sensing elements of the retina. Accelerated heavy ions of helium and neon from the Berkeley Bevalac were used. A number of criteria were chosen to characterize radiation damage by observing morphological changes with the scanning electron microscope. The studies indicated retina sensitivity to high-LET (neon) particles at radiation levels below 10 rads (7 particles per visual element) whereas no significant effects were seen from fast helium ions below 50 rads.

Malachowski, M. J.↗

Radiation environment of Spacelab-1

The results of passive and active radiation measurements on Spacelab-1 are reported. Spacelab-1 was flown on the STS-9 mission, orbited at an altitude of 241 km, with an inclination of 57 deg and 240 hours of flight time. Approximately thirty passive detectors deployed inside the module, in the access tunnel, and outside on the pallet made possible the radiation measurements. The various forms of radiation measured were a low linear energy transfer component ranging from 94 to 133 mrads inside the module (average dose rate of 10.0 mrads/day; about twice the rate of earlier shuttle flights), an average mission dose-equivalent rate of about 18.5 mrem/day (six times higher than earlier flights), accumulated doses of 125 and 128 mrads and a yield of 17 and 12 mrads for passages through the South Atlantic Anomaly. Spacelab-1, because of its low altitude and short duration, was relatively benign in terms of total radiation dose. Some of the measurements such as high-LET particles and neutrons have biological significance and potential effects on future experiments.

Benton, E. V.↗

Ionizing radiation exposure of LDEF (pre-recovery estimates)

The long duration exposure facility (LDEF), launched into a 258 nautical mile orbit with an inclination of 28.5 degrees, remained in space for nearly 6 yr. The 21,500 lb NASA satellite was one of the largest payloads ever deployed by the Space Shuttle. LDEF completed 32,422 orbits and carried 57 major experiments representing more than 200 investigators from 33 private companies, 21 universities and nine countries. The experiments covered a wide range of disciplines including basic science, electronics, optics, materials, structures and power and propulsion. A number of the experiments were specifically designed to measure the radiation environment. These experiments are of specific interest, since the LDEF orbit is essentially the same as that of the Space Station Freedom. Consequently, the radiation measurements on LDEF will play a significant role in the design of radiation shielding of the space station. The contributions of the various authors presented here attempt to predict the major aspects of the radiation exposure received by the various LDEF experiments and therefore should be helpful to investigators who are in the process of analyzing experiments which may have been affected by exposure to ionizing radiation. The paper discusses the various types and sources of ionizing radiation including cosmic rays, trapped particles (both protons and electrons) and secondary particles (including neutrons, spallation products and high-LET recoils), as well as doses and LET spectra as a function of shielding. Projections of the induced radioactivity of LDEF are also discussed.

Flight Experiment↗

Radiation dosimetry measurements during U.S. Space Shuttle missions with the RME-III

Time-resolved radiation dosimetry measurements inside the crew compartment have been made during recent Shuttle missions with the U.S. Air Force Radiation Monitoring Equipment-III (RME-III), a portable battery-powered four-channel tissue equivalent proportional counter. Results from the first six missions are presented and discussed. Half of the missions had orbital inclinations of 28.5 degrees with the remainder at inclinations of 57 degrees or greater; altitudes ranged from 300 to 600 km. The determined dose equivalent rates ranged from 70 to 5300 microSv/day. The RME-III measurements are in good agreement with other dosimetry measurements made aboard the vehicles. Measurements indicate that medium- and high-LET particles contribute less than 2% of the particle fluence for all missions, but up to 50% of the dose equivalent, depending on the spacecraft's altitude and orbital inclination. Isocontours of fluence, dose and dose equivalent rate have been developed from measurements made during the STS-28 mission. The drift rate of the South Atlantic Anomaly is estimated to be 0.49 degrees W/yr and 0.12 degrees N/yr. The calculated trapped proton and GCR dose for the STS-28 mission was significantly lower than the measured values.

STS-28 Shuttle Project↗

Model analysis of Space Shuttle dosimetry data

An extensive model analysis of plastic track detector measurements of high-LET particles on the Space Shuttle has been performed. Three Shuttle flights: STS-51F (low-altitude, high-inclination), STS-51J (high-altitude, low-inclination), and STS-61C (low-altitude, low-inclination) are considered. The model includes contributions from trapped protons and Galactic cosmic radiation, as well as target secondary particles. Target secondaries, expected to be of importance in thickly shielded space environments, are found to be a significant component of the measured LET (linear energy transfer) spectra.

Letaw, J. R.↗

Mutagenic effects of heavy ion radiation in plants

Genetic and developmental effects of heavy ions in maize and rice were investigated. Heavy particles with various charges and energies were accelerated at the BEVALAC. The frequency of occurrence of white-yellow stripes on leaves of plants developed from irradiated maize seeds increased linearly with dose, and high Linear Energy Transfer (LET) heavy charged particles, e.g., neon, argon, and iron, were 2-12 times as effective as gamma rays in inducing this type of mutation. The effectiveness of high-LET heavy ion in (1) inhibiting rice seedling growth, (2) reducing plant fertility, (3) inducing chromosome aberration and micronuclei in root tip cells and pollen mother cells of the first generation plants developed from exposed seeds, and (4) inducing mutation in the second generation, were greater than that of low-LET gamma rays. All effects observed were dose-dependent; however, there appeared to be an optimal range of doses for inducing certain types of mutation, for example, for argon ions (400 MeV/u) at 90-100 Gy, several valuable mutant lines with favorable characters, such as semidwarf, early maturity and high yield ability, were obtained. Experimental results suggest that the potential application of heavy ions in crop improvement is promising. Restriction-fragment-length-polymorphism (RFLP) analysis of two semidwarf mutants induced by argon particles revealed that large DNA alterations might be involved in these mutants.

Mei, M.↗