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Biomedical subjects

A B Cox

Publications and source records attributed to A B Cox.

At least 19 recordsLinked to original sources

Motivating signage prompts safety belt use among drivers exiting senior communities.

Senior drivers are vulnerable to automobile crashes and subsequent injury and death. Safety belts reduce health risks associated with auto crashes. Therefore, it is important to encourage senior drivers to wear safety belts while driving. Using an AB design, replicated five times, we evaluated the short- and long-term effects of a sign with the message "BUCKLE UP, STAY SAFE" attached to a stop sign at the exits of five different senior communities. Safety belt use was stable during two pretreatment assessments averaged across the five sites and 250 drivers (72% and 68% usage), but significantly increased following installation of these signs (94% usage). Six months after installation of the signs, the effect persisted (88% usage). Use of such signs may be a cost-effective way of promoting safety belt use.

Accidents, Traffic↗

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.

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↗

Induction of high grade astrocytoma (HGA) by protons: molecular mechanisms and RBE considerations.

Protons of a specific energy, 55 MeV, have been found to induce primary high grade astrocytomas (HGA) in the Rhesus monkey (Macaca mulatta). Brain tumors of this type were not induced by protons of other energies (32-2,300 MeV). Induction of HGA has been identified in human patients who have had radiation therapy to the head. We believe that the induction of HGA in the monkey is a consequence of dose distribution, not some unique "toxic" property of protons. Comparison of the human experience with the monkey data indicates the RBE for induction of brain tumors to be about one. It is unlikely that protons cause an unusual change in oncogenic expression, as compared to conventional electromagnetic radiation.

Animals↗

Helium-ion-induced human cataractogenesis.

Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoma patients treated with helium ions at 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.

Adult↗

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.

Aging↗

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.

Age Factors↗

Late cataractogenesis in primates and lagomorphs after exposure to particulate radiations.

Rhesus monkeys that were exposed in 1969, at the age of approximately 2 years, to low doses of "mixed-energy" protons (10- and 110-MeV) are exhibiting progressive (degenerative) lenticular changes. We have conducted regular examinations of this group of monkeys for cataractogenic development since 1987, i.e., 18 years after irradiation, and the animals began to show enhanced degrees of lenticular opacification two years later. The lenses of age-matched controls (median lifespan in captivity approximately 24 years) continue to exhibit much lower levels of opacification (senile cataracts). Trends in the new data are consistent with the cataractogenic patterns observed for other groups of monkeys that were exposed at similar ages in 1964 and 1965 to protons of different energies, and which we began to monitor only 20-21 years later. Therefore, the new information from the mixed-energy group of monkeys provides insight into the development of late cataractogenic sequelae in the other groups of animals during the 2-3 years before we began to measure them. Comparisons are also made here among recent results from the different groups of primates and from New Zealand white (NZW) rabbits that were exposed when young to 56Fe ions and monitored continuously thereafter. This is done because analogous expression of radiation-induced degenerative cataractogenesis also occurs late in the lifespan of the lagomorphs (control median lifespan in captivity approximately 5-7 years), but in this case the cataractogenic profile has been documented through most of the post-irradiation lifespan.

Animals↗

Late cataractogenesis in rhesus monkeys irradiated with protons and radiogenic cataract in other species.

Rhesus monkeys (Macaca mulatta) which were irradiated at ca. 2 years of age with acute doses (less than or equal to 5 Gy) of protons (32-2300 MeV) are exhibiting the late progressive phase of radiation cataractogenesis 20-24 years after exposure, the period during which we have been monitoring the sequelae of irradiation of the lens. The median life span of the primate is approximately 24 years. Analogous late ocular changes also occur in a similar period of the lifetimes of New Zealand White (NZW) rabbits (Oryctolagus cuniculus) exposed at 8-10 weeks of age to 460-MeV 56Fe ions. In this experiment, which has been in progress for ca. 6 years, we are following the development of radiation-induced lenticular opacification (cataractogenic profiles) throughout the life span. The median life span of the lagomorph is 5-7 years. Cataractogenic profiles for NZW rabbits irradiated with 20Ne and 40Ar ions and 60Co gamma photons were obtained previously. Reference is also made to measurements of the cataractogenic profiles of a short-lived rodent, the Fischer 344 rat (Rattus norvegicus) during the first year after exposure at 8-10 weeks of age to spread-Bragg-peak protons of 55 MeV nominal energy. The median life span of the rodent is reported to be 2-3 years.

Animals↗

Responses of synchronous L5178Y S/S cells to heavy ions and their significance for radiobiological theory.

Synchronous suspensions of the radiosensitive S/S variant of the L5178Y murine leukaemic lymphoblast at different positions in the cell cycle were exposed aerobically to segments of heavy-ion beams (20Ne, 28Si, 40Ar, 56Fe and 93Nb) in the Bragg plateau regions of energy deposition. The incident energies of the ion beams were in the range of 460 +/- 95 MeV u-1, and the calculated values of linear energy transfer (LET infinity) for the primary nuclei in the irradiated samples were 33 +/- 3, 60 +/- 3, 95 +/- 5, 213 +/- 21 and 478 +/- 36 keV microns-1, respectively; 280 kVp X-rays were used as the baseline radiation. Generally, the maxima or inflections in relations between relative biological effectiveness (RBE) and LET infinity were dependent upon the cycle position at which the cells were irradiated. Certain of those relations were influenced by post-irradiation hypothermia. Irradiation in the cell cycle at mid-G1 to mid-G1 + 3 h, henceforth called G1 to G1 + 3 h, resulted in survival curves that were close approximations to simple exponential functions. As the LET infinity was increased, the RBE did not exceed 1.0, and by 478 keV microns-1 it had fallen to 0.39. Although similar behaviour has been reported for inactivation of proteins and certain viruses by ionizing radiations, so far the response of the S/S variant is unique for mammalian cells. The slope of the survival curve for X-photons (D0: 0.27 Gy) is reduced in G1 to G1 + 3 h by post-irradiation incubation at hypothermic temperatures and reaches a minimum (Do: 0.51 Gy) at 25 degrees C. As the LET infinity was increased, however, the extent of hypothermic recovery was reduced progressively and essentially was eliminated at 478 keV microns-1. At the cycle position where the peak of radioresistance to X-photons occurs for S/S cells, G1 + 8 h, increases in LET infinity elicited only small increases in RBE (at 10% survival), until a maximum was reached around 200 keV microns-1. At 478 keV microns-1, what little remained of the variation in response through the cell cycle could be attributed to secondary radiations (delta rays) and smaller nuclei produced by fragmentation of the primary ions.

Animals↗

The role of repair in the survival of mammalian cells from heavy ion irradiation: approximation to the ideal case of target theory.

Theories of cellular radiation sensitivity that preclude a significant role for cellular repair processes in the final biological expression of cellular damage induced by ionizing radiation are unsound. Experiments are discussed here 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, 20Ne, 28Si, 40Ar, 56Fe and 93Nb. Evidence from those studies, which will be described in detail elsewhere, provide support for the notion that as the linear energy transfer (LET infinity) of the incident radiation increases the ability of the S/S cell to repair radiation damage decreases until effectively it is eliminated around 500 keV/micrometer. In the region of the latter LET infinity value, the behavior of the S/S cell approximates the ideal case of target theory where post-irradiation metabolism (repair) does not influence cell survival. The expression of this phenomenon among different cell types and tissues will depend upon the actual repair systems involved and other considerations.

Animals↗

The quantification of wound healing as a method to assess late radiation damage in primate skin exposed to high-energy protons.

In an experiment examining the effects of space radiations on primates, different groups of rhesus monkeys (Macaca mulatta) were exposed to single whole-body doses of 32- or 55-MeV protons. Survivors of those exposures, together with age-matched controls, have been monitored continuously since 1964 and 1965. Late effects of nominal proton doses ranging from 2-6 Gray have been measured in vitro using skin fibroblasts from the animals. A logical extension of that study is reported here, and it involves observations of wound healing after 3-mm diameter dermal punches were removed from the ears (pinnae) of control and irradiated monkeys. Tendencies in the reduction of competence to repair cutaneous wounds have been revealed by the initial examinations of animals that received doses greater than 2 Gy more than 2 decades earlier. These trends indicate that this method of assessing radiation damage to skin exposed to high-energy radiations warrants further study.

Animals↗

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 (NZW) 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 approximately 25 years, respectively; 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.

Animals↗

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).

Aging↗

Cellular and tissue responses to heavy ions: basic considerations.

Responses of the S/S variant of the L5178Y murine leukemic lymphoblast, the photoreceptor cell of the rabbit retina and the lenticular epithelium of the rabbit to heavy ions (20Ne, 28Si, 40Ar and 56Fe) are described and discussed primarily from the standpoint of the need for a comprehensive theory of cellular radiosensitivity from which a general theory of tissue radiosensitivity can be constructed. The radiation responses of the very radiosensitive, repair-deficient S/S variant during the G1- and early S phases of the cell cycle were found to be unlike those of normally radioresistant cells in culture: the relative biological effectiveness (RBE) did not increase with the linear energy transfer (LET infinity) of the incident radiation. Such behavior could be anticipated for a cell which is lacking the repair system that operates in other (normal) cells when they are exposed to ionizing radiations in the G1 phase of the cell cycle. The S/S variant does exhibit a peak of radioresistance to X-photons mid-G1 + 8 h into the cell cycle, however, and as the LET infinity was increased, the repair capacity responsible for that radioresistance was reduced progressively. Sensory cells (photoreceptors) in the retina of the New Zealand white (NZW) rabbit are very radioresistant to ionizing radiations, and several years elapsed after localized exposure (e.g., 5-10 Gy) to heavy ions (20Ne, 40Ar) before photoreceptor cells were lost from the retina. During the first few weeks after such irradiations, damage to DNA in the photoreceptor cells was repaired to a point where it could not be demonstrated by reorienting gradient sedimentation under alkaline conditions, a technique that can detect DNA damage produced by less than 0.1 Gy of X-photons. Restitution of DNA structure was not permanent, however, and months or years later, but before loss of photoreceptor cells from the retina could be detected, progressive deterioration of the DNA structure began. Age dependencies of late sequelae from densely ionizing radiations are matters of concern both for the therapeutic uses of radiation and the risk/benefit considerations of environmental exposure, especially in outer space. A pilot experiment with a single acute exposure to 20Ne ions has illustrated the need for careful examination of the role of animal age at the time of irradiation in subsequent tissue responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗