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Cox, A. B.

Publications and source records attributed to Cox, A. B..

At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1997

Dose reconstruction for individuals exposed to ionizing radiation using chromosome painting

To be most useful, a biomarker for dose reconstruction should employ an end point that is highly quantitative, stable with time and easily measured. Reciprocal translocations have been shown to be a promising biomarker that is linked to both prior exposure and risk, and they can be measured easily and quantitatively using fluorescence in situ hybridization. In contrast to other biomarkers that are available, the frequency of reciprocal translocations in individuals exposed to whole-body radiation is stable with time after exposure, has rather small interindividual variability and can be measured accurately at low levels of exposure. Results from recent studies demonstrate that measurements of reciprocal translocation frequencies, facilitated by chromosome painting, can be used to reconstruct radiation dose for individuals exposed in the distant past.

NASA Discipline Radiation Health↗
NASA NTRS1996

Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys

Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

Non-NASA Center↗
NASA NTRS1994

Helium-ion-induced human cataractogenesis

Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoman patients treated with helium ions at Lawrence Berkeley Laboratory (LBL) will allow examination of the exposure-response data for human cataract; which is a complication of the therapy from incidental exposure of the lens. Direct particle beam traversal of at least a portion of the lens usually is unavoidable in treatment of posterior intraocular tumors. The precise treatment planned for each patient permits quantitative assessment of the lenticular dose and its radiation quality. We are reporting our preliminary results on the development of helium-ion-induced lens opacifications and cataracts in 54 of these patients who had 10% or less of their lens in the treatment field. We believe these studies will be relevant to estimating the human risk for cataract in space flight.

Blakely, E. A.↗
NASA NTRS1994

Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.

Non-NASA Center↗
NASA NTRS1994

Effect of radiation and age on immunoglobulin levels in rhesus monkeys (Macaca mulatta)

We report the results of a study on the immunoglobulin levels of rhesus monkeys (Macaca mulatta) in a colony consisting of the survivors of monkeys that received a single whole-body exposure to protons, electrons or X rays between 1964 and 1969. This colony has been maintained to assess the long-term effects of ionizing radiation on astronauts and high-flying pilots. Of the original 358 monkeys that were retained for lifetime studies, 129 (97 irradiated and 32 controls) were available for our study. We found no significant difference between the irradiated and control monkeys in mean levels of IgA, IgG and IgM, irrespective of the radiation treatment. The availability of these aged monkeys provided a unique opportunity to compare their immunoglobulin levels to those of other monkeys of various ages, and thus assess the effect of age on immunoglobulin levels. We found that only the IgA levels increase with age.

Non-NASA Center↗
NASA NTRS1992

Late cataractogenesis in primates and lagomorphs after exposure to particulate radiations

Results are presented from a study in which regular examinations of cataractogenic development were conducted since 1987 in monkeys that were exposed in 1969, at the age of about 2 years, to low doses of 'mixed-energy' protons (10 and 110 MeV). The results of comparisons with age-matched controls showed that the cataractogenic patterns observed in the exposed monkeys are consistent with those observed in other groups of monkeys that were exposed at similar ages in 1964 and 1965 to protons of different energies (Lett et al., 1986, 1988, 1989, and 1991). Comparisons were also made among recent results from different groups of primates and from New Zealand white rabbits that were exposed when young to Fe-56 and were monitored continuously thereafter.

Cox, A. B.↗
NASA NTRS1991

A study of lens opacification for a Mars mission

A method based on risk-related cross sections is used to estimate risks of 'stationary' cataracts caused by radiation exposures during extended missions in deep space. Estimates of the even more important risk of late degenerative cataractogenesis are made on the basis of the limited data available. Data on lenticular opacification in the New Zealand white rabbit, an animal model from which such results can be extrapolated to humans, are analyzed by the Langley cosmic ray shielding code (HZETRN) to generate estimates of stationary cataract formation resulting from a Mars mission. The effects of the composition of shielding material and the relationship between risk and LET are given, and the effects of target fragmentation on the risk coefficients are evaluated explicitly.

Shinn, J. L.↗
NASA NTRS1989

The role of repair in the survival of mammalian cells from heavy ion irradiation - Approximation to the ideal case of target theory

Experiments are discussed in which the cell-cycle dependency of the repair deficiency of the S/S variant of the L5178Y murine leukemic lymphoblast was examined by treatment with the heavy ions, Ne-20, Si-28, Ar-40, Fe-56, and Nb-93. Evidence from those studies provide support for the notion that as the linear energy transfer of the incident radiation increases the ability of the S/S cell to repair radiation damage decreases until it is eliminated around 500 keV/micron. In the region of the latter linear energy transfer value, the behavior of the S/S cell approximates the ideal case of target theory where post-irradiation metabolism does not influence cell survival.

Lett, J. T.↗
NASA NTRS1989

Late cataractogenesis caused by particulate radiations and photons in long-lived mammalian species

Radiation cataractogenesis induced by small acute doses of particulate radiations and photons in the New Zealand white rabbit (Oryctolagus cuniculus), the beagle dog (Canis familiaris) and the rhesus monkey (Macaca mulatta) is discussed in the context of the use of animal models to assess the radiation hazards faced by humans during lengthy sojourns in deep space. Attention is paid to (1) the importance of lifespan studies with long-lived species - the above animals have median lifespans in captivity of 5-7, 13-14 and 25 years, respectively; and (2) the magnitudes of possible dose thresholds for cataractogenesis from sparsely ionizing radiations and the modifications of those thresholds by the late degenerative phase of the phenomenon.

Lett, J. T.↗
NASA NTRS1988

Age dependency of base modification in rabbit liver DNA

Age-related modifications of DNA bases have been observed in the liver of the New Zealand white (NZW) rabbit (Oryctolagus cuniculus), a lagomorph with a median life span in captivity of 5-7 yr. The ages of the animals studied ranged from 6 wk to 9 yr. After the DNA had been extracted from the liver cell nuclei and hydrolyzed with acid, the bases were analyzed by column chromatography with Cellulofine gels (GC-15-m). Two peaks in the chromatogram, which eluted before the four DNA bases, contained modified bases. Those materials, which were obtained in relatively large amounts from old animals, were highly fluorescent, and were shown to be crosslinked base products by mass spectrometry. The yield of crosslinked products versus rabbit age (greater than 0.5 yr) can be fitted by an exponential function (correlation coefficient: 0.76 +/- 0.09).

NASA Discipline Radiation Health↗
NASA NTRS1986

Morphometric studies of heavy ion damage in the brains of rodents

The relative biological effectiveness (RBE) of different heavy ions for the mammalian brain was determined in mice irradiated at 100 days of age with He-4, C-12, Ne-20, Fe-56, Ar-40, or Co-60 gamma photons (with the primary particle LET values ranging from 2 to 650). Brain preparations were examined 16 months later for volume changes in the external plexiform layer (P-zone) of the olfactory bulb and an internal region (G-zone), which consists of the granule cells, the internal plexiform layer, and the mitral cell layer. The result indicate that the volume changes did occur in the olfactory bulb, not only in absolute terms but also when expressed as the ratio of the structures to each other and to the bulb as a whole. While the observed increased neuronal loss in mice receiving 700 cGy of Co-60 support the earlier data from irradiated rabbits, the increases observed in bulbar volumes and in the volume ratios of the P and the G zones measured in the mice given lower doses (320 or 160 cGy of He or C), were not expected.

Kraft, L. M.↗
NASA NTRS1986

Cataractogenic potential of ionizing radiations in animal models that simulate man

Aspects of experiments on radiation-induced lenticular opacification during the life spans of two animal models, the New Zealand white rabbit and the rhesus monkey, are compared and contrasted with published results from a life-span study of another animal model, the beagle dog, and the most recent data from the ongoing study of the survivors from radiation exposure at Hiroshima and Nagasaki. An important connection among the three animal studies is that all the measurements of cataract indices were made by one of the authors (Lee), so variation from personal subjectivity was reduced to a minimum. The primary objective of the rabbit experiments (radiations involved: Fe-56, Ar-40, and Ne-20 ions and Co-60 gamma photons) is an evaluation of hazards to astronauts from Galactic particulate radiations. An analogous evaluation of hazards from solar flares during space flight is being made with monkeys exposed to 32, 55, 138 and 400-MeV protons. Conclusions are drawn about the proper use of animal models to simulate radiation responses in man and the levels of radiation-induced lenticular opacification that pose risks to man in space.

Lett, J. T.↗
NASA NTRS1984

Quantitation of heavy ion damage to the mammalian brain - Some preliminary findings

For several years, studies have been conducted regarding late effects of particulate radiations in mammalian tissues, taking into account the brains of rodents and lagomorphs. Recently, it has become feasible to quantify pathological damage and morpho-physiologic alterations accurately in large numbers of histological specimens. New investigative procedures make use of computer-assisted automated image analysis systems. Details regarding the employed methodology are discussed along with the results of the information. The radiations of high linear energy transfer (LET) cause apparently earlier and more dramatic shrinkage of olfactory glomeruli in exposed rabbit brains than comparable doses of Co-60 gamma photons.

Cox, A. B.↗
NASA NTRS1984

Late effects from particulate radiations in primate and rabbit tissues

In connection with studies regarding the hazards posed by ionizing radiations to man in space, the U.S. Air Force conducted an experiment about 20 years ago. In this experiment a large number of young rhesus monkeys was exposed to proton fluxes similar to those to be anticipated during solar flares. After irradiation, the animals were kept at the USAF School of Aerospace Medicine in Texas. The monkeys have been employed in investigations concerning aspects of late radiation damage. These investigations are discussed, taking into account the propagation of fibroblasts from irradiated monkeys. The results of the investigations are evaluated, giving attention also to experiments with white rabbits. It is found that, except in the case of major solar flares, when acute radiation damage could lead quickly to death, the hazards to astronauts from space radiations arise from such debilitating late effects as cataracts, damage to the central nervous system and benign tumors, and life-threatening neoplasia.

Lett, J. T.↗
NASA NTRS1983

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.↗