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At least 19 recordsLinked to original sources

Radiation effects in Caenorhabditis elegans, mutagenesis by high and low LET ionizing radiation.

The nematode C. elegans was used to measure the effectiveness of high-energy ionized particles in the induction of 3 types of genetic lesions. Recessive lethal mutations in a 40-map unit autosomal region, sterility, and X-chromosome nondisjunction or damage were investigated. Induction rates were measured as a function of linear energy transfer, LET infinity, for 9 ions of atomic number 1-57 accelerated at the BEVALAC accelerator. Linear kinetics were observed for all 3 types of lesions within the dose/fluence ranges tested and varied strongly as a function of particle LET infinity. Relative Biological Effectiveness (RBE) values of up to 4.2 were measured and action cross sections were calculated and compared to mutagenic responses in other systems.

Animals↗

Caenorhabditis elegans: a model system for space biology studies.

The utility of the nematode Caenorhabditis elegans in studies spanning aspects of development, aging, and radiobiology is reviewed. These topics are interrelated via cellular and DNA repair processes especially in the context of oxidative stress and free-radical metabolism. The relevance of these research topics to problems in space biology is discussed and properties of the space environment are outlined. Exposure to the space-flight environment can induce rapid changes in living systems that are similar to changes occurring during aging; manipulation of these environmental parameters may represent an experimental strategy for studies of development and senscence. The current and future opportunities for such space-flight experimentation are presented.

Aging↗

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↗

Use of non-subjective analysis of lens transparency in experimental radiation cataract research.

Historically the major impediment to radiation cataract follow-up has been the necessarily subjective nature of assessing the degree of lens transparency. This has spurred the development of instruments which produce video images amenable to digital analysis. One such system, the Zeiss Scheimpflug slit lamp measuring system (SLC), was incorporated into our ongoing studies of radiation cataractogenesis. It was found that the Zeiss SLC measuring system has high resolution and permits the acquisition of reproducible images of the anterior segment of the eye. Our results, based on about 650 images of lenses followed over a period of 91 weeks of radiation cataract development, showed that the changes in the light scatter of the lens correlated well with conventional assessment of radiation cataracts with the added advantages of objectivity, permanent and transportable records and linearity as cataracts become more severe. This continuous data acquisition, commencing with cataract onset, can proceed through more advanced stages. The SLC exhibits much greater sensitivity reflected in a continuously progressive severity thereby avoiding the artifactual plateaus in staging which occur using conventional scoring methods.

Animals↗

Interplanetary crew exposure estimates for the August 1972 and October 1989 solar particle events.

Using the coupled neutron-proton space radiation transport computer code (BRYNTRN), estimates of human exposure in interplanetary space, behind various thicknesses of aluminum shielding, are made for the large solar proton events of August 1972 and October 1989. A comparison of risk assessment in terms of total absorbed dose for each event is made for the skin, ocular lens, and bone marrow. Overall, the doses associated with the August 1972 event were higher than those with the October 1989 event and appear to be more limiting when compared with current guidelines for dose limits for missions in low Earth orbit and more hazardous with regard to potential acute effects on these organs. Both events could be life-threatening if adequate shielding is not provided.

Bone Marrow↗

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.

Animals↗

Accelerated heavy particles and the lens. VIII. Comparisons between the effects of acute low doses of iron ions (190 keV/microns) and argon ions (88 keV/microns).

The nature of the RBE-LET relationship for radiation-induced effects in vivo is not well known in the high-LET range above about 100 keV/microns. Here, we compare the cataractogenic effects of acute doses of 190 keV/microns iron ions on the eyes of rats with those of 88 keV/microns argon ions. The RBEs of the two radiations cannot be distinguished statistically, both being between 50 and 200 at our lowest dose of 0.01 Gy and decreasing to between 2 and 14 at our highest dose of 0.5 Gy; these values are consistent with results obtained in vivo, both for cataractogenesis and for oncogenesis. For this end point, therefore, the RBE-LET relationship probably varies very slowly between 88 and 190 keV/microns. On the basis of these studies with acute doses of 88 and 190 keV/microns particles, the detailed distribution in LET of the very high-LET galactic cosmic-ray dose to which astronauts in deep space are exposed may not be critical for the prediction of biological hazard. Such a conclusion might simplify the task of high-LET radiation risk estimation in space.

Animals↗

Alveolar ventilation to perfusion heterogeneity and diffusion impairment in a mathematical model of gas exchange.

This study describes a two-compartment model of pulmonary gas exchange in which alveolar ventilation to perfusion (VA/Q) heterogeneity and impairment of pulmonary diffusing capacity (D) are simultaneously taken into account. The mathematical model uses as input data measurements usually obtained in the lung function laboratory. It consists of two compartments and an anatomical shunt. Each compartment receives fractions of alveolar ventilation and blood flow. Mass balance equations and integration of Fick's law of diffusion are used to compute alveolar and blood O2 and CO2 values compatible with input O2 uptake and CO2 elimination. Two applications are presented. The first is a method to partition O2 and CO2 alveolar-arterial gradients into VA/Q and D components. The technique is evaluated in data of patients with chronic obstructive pulmonary disease (COPD). The second is a theoretical analysis of the effects of blood flow variation in alveolar and blood O2 partial pressures. The results show the importance of simultaneous consideration of D to estimate VA/Q heterogeneity in patients with diffusion impairment. This factor plays an increasing role in gas alveolar-arterial gradients as severity of COPD increases. Association of VA/Q heterogeneity and D may produce an increase of O2 arterial pressure with decreasing QT which would not be observed if only D were considered. We conclude that the presented computer model is a useful tool for description and interpretation of data from COPD patients and for performing theoretical analysis of variables involved in the gas exchange process.

Blood Gas Monitoring, Transcutaneous↗

Toxicokinetics of inhaled bromotrifluoromethane (Halon 1301) in human subjects.

Bromotrifluoromethane (CBrF3), commonly known as Halon 1301, is used as a fire extinguishant in the Space Shuttle. Several scenarios, such as a fire or a faulty alarm, could lead to its discharge resulting in a Halon 1301 concentration of up to 1% in the spacecraft cabin atmosphere. To examine the effects of Halon 1301 on mental performance and physiologic function, the National Aeronautics and Space Administration sponsored a human inhalation study. Four pairs of adult male subjects were each exposed in a double-blind fashion for 24 hr to 1% (10,000 ppm or 60,875 mg/m3) Halon 1301 and to air in two separate exposures approximately 1 week apart. Mental performance and physiologic function were assessed and the results are reported in a companion paper (D. S. Calkins, J. J. Degioanni, M. N. Tan, J. R. Davis, and D. L. Pierson. Fundam. Appl. Toxicol. 20, in press). Blood and breath samples from the exposed subjects were also collected to provide dosimetric and toxicokinetic information, which is presented here. Blood Halon 1301 levels increased rapidly and approached a steady state within 2 hr of beginning the exposure; the steady-state concentration was approximately 3-4.5 micrograms/ml. Breath samples collected during exposures closely reflected chamber concentrations. Analysis of postexposure blood samples revealed that Halon 1301 was eliminated biphasically with an average t1/2 alpha and t1/2 beta of 4.5 min (range 2.5-8.1 min) and 200 min (range 131-347 min), respectively. Halon 1301 concentrations in fat and soft tissues were also estimated. Subsequently, the end-tidal breath/blood/tissue/fat partition coefficients were calculated to be 17/1/0.5/33.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Human performance and physiological function during a 24-hr exposure to 1% bromotrifluoromethane (Halon 1301).

Performance and physiological measurements were obtained from four pairs of men exposed for 24 hr to 1% (10,000 ppm) Halon 1301 (bromotrifluoromethane, CBrF3) and to air with order counterbalanced using a double-blind protocol. Cognitive and motor performance was assessed before, during, and after the exposures using seven scales of the Automated Portable Testing System, which produced 13 measures of performance. Halon inhalation induced decrements in 2 of the 13 measures, but actual and estimated magnitudes of the decrements were no greater than 5% of baseline values. Physiological data were obtained before, during, and after the exposures from clinical chemistry analyses of blood and urine samples, pulmonary function tests, and monitoring of vital signs. Significant change during Halon inhalation was observed for 6 of the 52 variables assessed; however, all physiological values remained within clinically acceptable limits. No cardiovascular effects were noted. This study demonstrated that exposure to 1% Halon 1301 for 24 hr can produce minor disturbance of central nervous system function as assessed by cognitive tasks.

Administration, Inhalation↗

Fungal colonization of fiberglass insulation in the air distribution system of a multi-story office building: VOC production and possible relationship to a sick building syndrome.

Complaints characteristic of those for sick building syndrome prompted mycological investigations of a modern multi-story office building on the Gulf coast in the Southeastern United States (Houston-Galveston area). The air handling units and fiberglass duct liner of the heating, ventilating and air conditioning system of the building, without a history of catastrophic or chronic water damage, demonstrated extensive colonization with Penicillium spp and Cladosporium herbarum. Although dense fungal growth was observed on surfaces within the heating-cooling system, most air samples yielded fewer than 200 CFU m-3. Several volatile compounds found in the building air were released also from colonized fiberglass. Removal of colonized insulation from the floor receiving the majority of complaints of mouldy air and continuous operation of the units supplying this floor resulted in a reduction in the number of complaints.

Air Conditioning↗

Evaluation of the Biolog MicroStation system for yeast identification.

One hundred and fifty-nine isolates representing 16 genera and 53 species of yeasts were processed with the Biolog MicroStation System for yeast identification. Thirteen genera and 38 species were included in the Biolog database. For these 129 isolates, correct identifications to the species level were 13.2, 39.5 and 48.8% after 24, 48 and 72 hours incubation at 30 degrees C, respectively. Three genera and 15 species which were not included in the Biolog database were also tested. Of the 30 isolates studied, 16.7, 53.3 and 56.7% of the isolates were given incorrect names from the system's database after 24,48 and 72 h incubation at 30 degrees C, respectively. The remaining isolates of this group were not identified.

Candida↗

Effects of substrates and phosphate on INT (2-(4-iodophenyl)-3-(4-nitrophenyl)-5-phenyl tetrazolium chloride) and CTC (5-cyano-2,3-ditolyl tetrazolium chloride) reduction in Escherichia coli.

The effects of substrates of primary aerobic dehydrogenases, and inorganic phosphate on aerobic INT and CTC reduction in Escherichia coli were examined. In general, INT produced less formazan than CTC, but INT (+) cell counts remained near values of CTC (+) cells. INT and CTC (+) cell numbers were higher than plate counts on R2A medium using succinate, formate, lactate, casamino acids, glucose, glycerol (INT only) and no substrate. Formate resulted in the greatest amount of INT and CTC formazan. Reduction of both INT and CTC was inhibited above 10 mmol l-1 phosphate, and this appeared to be related to decreased rates of O2 consumption. Formation of fluorescent CTC (+), but not INT (+) cells was also inhibited in a concentration dependent manner by phosphate above 10 mmol l-1. From light microscopic observations it appeared CTC formed increasing amounts of poorly or non-fluorescent formazan with increasing phosphate. Therefore, use of phosphate buffer in excess of 10 mmol l-1 may not be appropriate in CTC and INT reduction assays.

Colony Count, Microbial↗

Acute mountain sickness: increased severity during simulated altitude compared with normobaric hypoxia.

Acute mountain sickness (AMS) strikes those in the mountains who go too high too fast. Although AMS has been long assumed to be due solely to the hypoxia of high altitude, recent evidence suggests that hypobaria may also make a significant contribution to the pathophysiology of AMS. We studied nine healthy men exposed to simulated altitude, normobaric hypoxia, and normoxic hypobaria in an environmental chamber for 9 h on separate occasions. To simulate altitude, the barometric pressure was lowered to 432 +/- 2 (SE) mmHg (simulated terrestrial altitude 4,564 m). Normobaric hypoxia resulted from adding nitrogen to the chamber (maintained near normobaric conditions) to match the inspired PO2 of the altitude exposure. By lowering the barometric pressure and adding oxygen, we achieved normoxic hypobaria with the same inspired PO2 as in our laboratory at normal pressure. AMS symptom scores (average scores from 6 and 9 h of exposure) were higher during simulated altitude (3.7 +/- 0.8) compared with either normobaric hypoxia (2.0 +/- 0.8; P < 0.01) or normoxic hypobaria (0.4 +/- 0.2; P < 0.01). In conclusion, simulated altitude induces AMS to a greater extent than does either normobaric hypoxia or normoxic hypobaria, although normobaric hypoxia induced some AMS.

Acute Disease↗

Cardiovascular pressures with venous gas embolism and decompression.

Venous gas embolism (VGE) is reported with decompression to a decreased ambient pressure. With severe decompression, or in cases where an intracardiac septal defect (patent foramen ovale) exists, the venous bubbles can become arterialized and cause neurological decompression illness. Incidence rates of patent foramen ovale in the general population range from 25-34% and yet aviators, astronauts, and deepsea divers who have decompression-induced venous bubbles do not demonstrate neurological symptoms at these high rates. This apparent disparity may be attributable to the normal pressure gradient across the atria of the heart that must be reversed for there to be flow patency. We evaluated the effects of: a) venous gas embolism (0.025, 0.05 and 0.15 ml.kg-1.min-1 for 180 min.); b) hyperbaric decompression; and c) hypobaric decompression on the pressure gradient across the left and right atria in anesthetized dogs with intact atrial septa. Left ventricular end-diastolic pressure was used as a measure of left atrial pressure. In a total of 92 experimental evaluations in 22 dogs, there were no reported reversals in the mean pressure gradient across the atria; a total of 3 transient reversals occurred during the peak pressure gradient changes. The reasons that decompression-induced venous bubbles do not consistently cause serious symptoms of decompression illness may be that the amount of venous gas does not always cause sufficient pressure reversal across a patent foramen ovale to cause arterialization of the venous bubbles.

Altitude↗