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Results for “Dose-Response Relationship, Radiation”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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142 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRS2001

Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor

The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 +/- 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects' pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 0.91), which identifies 446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.

Non-NASA Center↗
NASA NTRS2000

Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness

Light can elicit both circadian and acute physiological responses in humans. In a dose response protocol men and women were exposed to illuminances ranging from 3 to 9100 lux for 6.5 h during the early biological night after they had been exposed to <3 lux for several hours. Light exerted an acute alerting response as assessed by a reduction in the incidence of slow-eye movements, a reduction of EEG activity in the theta-alpha frequencies (power density in the 5-9 Hz range) as well as a reduction in self-reported sleepiness. This alerting response was positively correlated with the degree of melatonin suppression by light. In accordance with the dose response function for circadian resetting and melatonin suppression, the responses of all three indices of alertness to variations in illuminance were consistent with a logistic dose response curve. Half of the maximum alerting response to bright light of 9100 lux was obtained with room light of approximately 100 lux. This sensitivity to light indicates that variations in illuminance within the range of typical, ambient, room light (90-180 lux) can have a significant impact on subjective alertness and its electrophysiologic concomitants in humans during the early biological night.

Clinical Trial↗
NASA NTRS2000

Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression

Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

NASA Discipline Regulatory Physiology↗
NASA NTRS1996

Dose-response relationships for resetting of human circadian clock by light

Since the first report in unicells, studies across diverse species have demonstrated that light is a powerful synchronizer which resets, in an intensity-dependent manner, endogenous circadian pacemakers. Although it is recognized that bright light (approximately 7,000 to 13,000 lux) is an effective circadian synchronizer in humans, it is widely believed that the human circadian pacemaker is insensitive to ordinary indoor illumination (approximately 50-300 lux). It has been proposed that the relationship between the resetting effect of light and its intensity follows a compressive nonlinear function, such that exposure to lower illuminances still exerts a robust effect. We therefore undertook a series of experiments which support this hypothesis and report here that light of even relatively low intensity (approximately 180 lux) significantly phase-shifts the human circadian pacemaker. Our results clearly demonstrate that humans are much more sensitive to light than initially suspected and support the conclusion that they are not qualitatively different from other mammals in their mechanism of circadian entrainment.

NASA Discipline Regulatory Physiology↗
NASA NTRS2004

Green-light supplementation for enhanced lettuce growth under red- and blue-light-emitting diodes

Plants will be an important component of future long-term space missions. Lighting systems for growing plants will need to be lightweight, reliable, and durable, and light-emitting diodes (LEDs) have these characteristics. Previous studies demonstrated that the combination of red and blue light was an effective light source for several crops. Yet the appearance of plants under red and blue lighting is purplish gray making visual assessment of any problems difficult. The addition of green light would make the plant leave appear green and normal similar to a natural setting under white light and may also offer a psychological benefit to the crew. Green supplemental lighting could also offer benefits, since green light can better penetrate the plant canopy and potentially increase plant growth by increasing photosynthesis from the leaves in the lower canopy. In this study, four light sources were tested: 1) red and blue LEDs (RB), 2) red and blue LEDs with green fluorescent lamps (RGB), 3) green fluorescent lamps (GF), and 4) cool-white fluorescent lamps (CWF), that provided 0%, 24%, 86%, and 51% of the total PPF in the green region of the spectrum, respectively. The addition of 24% green light (500 to 600 nm) to red and blue LEDs (RGB treatment) enhanced plant growth. The RGB treatment plants produced more biomass than the plants grown under the cool-white fluorescent lamps (CWF treatment), a commonly tested light source used as a broad-spectrum control.

Non-NASA Center↗
NASA NTRS2004

Effect of high-dose irradiation on the optically stimulated luminescence of Al2O3:C

This paper examines the effect of high-dose irradiation on the optically stimulated luminescence (OSL) of Al2O3:C, principally on the shape of the OSL decay curve and on the OSL sensitivity. The effect of the degree of deep trap filling on the OSL was also studied by monitoring the sensitivity changes after doses of beta irradiation and after step-annealing of samples previously irradiated with high doses. The OSL response to dose shows a linear-supralinear-saturation behavior, with a decrease in the response for doses higher than those required for saturation. This behavior correlates with the sensitivity changes observed in the samples annealed only to 773 K, which show sensitization for doses up to 20-50 Gy and desensitization for higher doses. Data from the step-annealing study leads to the suggestion that the sensitization is caused by the filling of deep electron traps, which become thermally unstable at 1100-1200 K, whereas the desensitization is caused by the filling of deep hole traps, which become thermally unstable at 800-875 K, along with a concomitant decrease in the concentration of recombination centers (F+ -centers). Changes in the shape of the OSL decay curves are also observed at high doses, the decay becoming faster as the dose increases. These changes in the OSL decay curves are discussed in terms of multiple overlapping components, each characterized by different photoionization cross-sections. However, using numerical solutions of the rate equations for a simple model consisting of a main trap and a recombination center, it is shown that the kinetics of OSL process may also be partially responsible for the changes in the OSL curves at high doses in Al2O3:C. Finally, the implication of these results for the dosimetry of heavy charged particles is discussed. c2004 Elsevier Ltd. All rights reserved.

Heavy Ions↗
NASA NTRS2003

Radiation-induced second cancers: the impact of 3D-CRT and IMRT

Information concerning radiation-induced malignancies comes from the A-bomb survivors and from medically exposed individuals, including second cancers in radiation therapy patients. The A-bomb survivors show an excess incidence of carcinomas in tissues such as the gastrointestinal tract, breast, thyroid, and bladder, which is linear with dose up to about 2.5 Sv. There is great uncertainty concerning the dose-response relationship for radiation-induced carcinogenesis at higher doses. Some animal and human data suggest a decrease at higher doses, usually attributed to cell killing; other data suggest a plateau in dose. Radiotherapy patients also show an excess incidence of carcinomas, often in sites remote from the treatment fields; in addition there is an excess incidence of sarcomas in the heavily irradiated in-field tissues. The transition from conventional radiotherapy to three-dimensional conformal radiation therapy (3D-CRT) involves a reduction in the volume of normal tissues receiving a high dose, with an increase in dose to the target volume that includes the tumor and a limited amount of normal tissue. One might expect a decrease in the number of sarcomas induced and also (less certain) a small decrease in the number of carcinomas. All around, a good thing. By contrast, the move from 3D-CRT to intensity-modulated radiation therapy (IMRT) involves more fields, and the dose-volume histograms show that, as a consequence, a larger volume of normal tissue is exposed to lower doses. In addition, the number of monitor units is increased by a factor of 2 to 3, increasing the total body exposure, due to leakage radiation. Both factors will tend to increase the risk of second cancers. Altogether, IMRT is likely to almost double the incidence of second malignancies compared with conventional radiotherapy from about 1% to 1.75% for patients surviving 10 years. The numbers may be larger for longer survival (or for younger patients), but the ratio should remain the same.

Review, Tutorial↗
NASA NTRS2003

Stereology techniques in radiation biology

Clinicians involved in conventional radiation therapy are very concerned about the dose-response relationships of normal tissues. Before proceeding to new clinical protocols, radiation biologists involved with conformal proton therapy believe it is necessary to quantify the dose response and tolerance of the organs and tissues that will be irradiated. An important focus is on the vasculature. This presentation reviews the methodology and format of using confocal microscopy and stereological methods to quantify tissue parameters, cell number, tissue volume and surface area, and vessel length using the microvasculature as a model tissue. Stereological methods and their concepts are illustrated using an ongoing study of the dose response of the microvessels in proton-irradiated hemibrain. Methods for estimating the volume of the brain and the brain cortex, the total number of endothelial cells in cortical microvessels, the length of cortical microvessels, and the total surface area of cortical microvessel walls are presented step by step in a way understandable for readers with little mathematical background. It is shown that stereological techniques, based on a sound theoretical basis, are powerful and reliable and have been used successfully.

Non-NASA Center↗
NASA NTRS1999

Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers

The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.

Non-NASA Center↗
NASA NTRS1995

Radiogenic cell transformation and carcinogenesis

Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic mechanism(s) of radiogenic transformation of human epithelial cells.

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 NTRS1999

A Novel Technique for Performing Space Based Radiation Dosimetry Using DNA: Results from GRaDEx-I and the Design of GRaDEx-II

Because of the large amounts of cosmic radiation in the space environment relative to that on earth, the effects of radiation on the physiology of astronauts is of major concern. Doses of radiation which can cause acute or chronic biological effects are to be avoided, therefore determination of the amount of radiation exposure encountered during space flight and assessment of its impact on biological systems is critical. Quantifying the radiation dosage and damage to biological systems, especially to humans during repetitive high altitude flight and during long duration space flight is important for several reasons. Radiation can cause altered biosynthesis and long term genotoxicity resulting in cancer and birth defects, etc. Radiation damage to biological systems depends in a complex way on incident radiation species and their energy spectra. Typically non-biological, i.e. film or electronic monitoring systems with narrow energy band sensitivity are used to perform dosimetry and then results are extrapolated to biological models. For this reason it may be desirable to perform radiation dosimetry by using biological molecules e.g. DNA or RNA strands as passive sensors. A lightweight genotoxicology experiment was constructed to determine the degree to which in-vitro naked DNA extracted from tissues of a variety of vertebrate organisms is damaged by exposure to radiation in a space environment. The DNA is assayed by means of agarose gel electrophoresis to determine damage such as strand breakage caused by high momentum particles and photons, and base oxidation caused by free radicals. The length distribution of DNA fragments is directly correlated with the radiation dose. It is hoped that a low mass, low cost, passive biological system to determine dose-response relationship (increase in strand breaks with increase in exposure) can be developed to perform radiation dosimetry in support of long duration space flight, and to predict negative effects on biological systems (e.g. astronauts and greenhouses) in space. The payload was flown in a 2.5 cubic foot Get Away Special (GAS) container through NASA's GAS program. It was subjected to the environment of the space shuttle cargo bay for the duration of the STS-91 mission (9 days). Results of the genotoxicology and radiation dosimetry experiment (GRaDEx-I) as well as the design of an improved follow on payload are presented.

Ritter, Joe↗
NASA NTRS2003

An algorithm for neurite outgrowth reconstruction

We present a numerical method which provides the ability to analyze digitized microscope images of retinal explants and quantify neurite outgrowth. Few parameters are required as input and limited user interaction is necessary to process an entire experiment of images. This eliminates fatigue related errors and user-related bias common to manual analysis. The method does not rely on stained images and handles images of variable quality. The algorithm is used to determine time and dose dependent, in vitro, neurotoxic effects of 1 GeV per nucleon iron particles in retinal explants. No neurotoxic effects are detected until 72 h after exposure; at 72 h, significant reductions of neurite outgrowth occurred at doses higher than 10 cGy.

NASA Program Biomedical Research and Countermeasur↗
NASA NTRS1989

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↗
NASA NTRS2003

Complex formation by the human Rad51B and Rad51C DNA repair proteins and their activities in vitro

The human Rad51 protein is essential for DNA repair by homologous recombination. In addition to Rad51 protein, five paralogs have been identified: Rad51B/Rad51L1, Rad51C/Rad51L2, Rad51D/Rad51L3, XRCC2, and XRCC3. To further characterize a subset of these proteins, recombinant Rad51, Rad51B-(His)(6), and Rad51C proteins were individually expressed employing the baculovirus system, and each was purified from Sf9 insect cells. Evidence from nickel-nitrilotriacetic acid pull-down experiments demonstrates a highly stable Rad51B.Rad51C heterodimer, which interacts weakly with Rad51. Rad51B and Rad51C proteins were found to bind single- and double-stranded DNA and to preferentially bind 3'-end-tailed double-stranded DNA. The ability to bind DNA was elevated with mixed Rad51 and Rad51C, as well as with mixed Rad51B and Rad51C, compared with that of the individual protein. In addition, both Rad51B and Rad51C exhibit DNA-stimulated ATPase activity. Rad51C displays an ATP-independent apparent DNA strand exchange activity, whereas Rad51B shows no such activity; this apparent strand exchange ability results actually from a duplex DNA destabilization capability of Rad51C. By analogy to the yeast Rad55 and Rad57, our results suggest that Rad51B and Rad51C function through interactions with the human Rad51 recombinase and play a crucial role in the homologous recombinational repair pathway.

Non-NASA Center↗
NASA NTRS2005

Protective effect of apigenin on radiation-induced chromosomal damage in human lymphocytes

The potential use of flavonoids as a radioprotector is of increasing interest because of their high antioxidant activity and abundance in the diet. The aim of this study is to examine genotoxic and radioprotective effects of one of the most common flavonoids, apigenin, on radiation-induced chromosome aberrations in human lymphocytes. The cytokinesis-block micronucleus (CBMN) assay was used to evaluate such effects of apigenin. Blood samples were collected from two non-smoking healthy male volunteers who had no history of previous exposure to other clastogenic agents. Isolated lymphocytes were cultured. There were two tubes per concentration for all treatments. To evaluate the genotoxicity of apigenin, cells were first treated with different concentrations of apigenin (0, 2.5, 5, 10 and 25 microg/mL) at 24 h after culture initiation, followed by cytochalasin-B (Cyt-B) treatment (3 microg/mL) and cell harvest at 44 and 72 h, respectively. Secondly, to investigate the radioprotective effect, cell cultures were exposed to different concentrations of apigenin as described above for 30 min before being irradiated to 2 Gy of 137Cs gamma rays (at a dose rate of 0.75 Gy/min). In all instances, the frequency of MN was scored in binucleated (BN) cells. The nuclear proliferation index also was calculated. We did not detect an increase in the frequency of MN in non-irradiated human lymphocyte cultures treated with 2.5, 5.0 or 10 microg/mL apigenin; although, we did observe an increase in cultures treated with 25 microg/mL apigenin (the highest concentration of apigenin used in our study). We also observed a significant increase in the frequency of MN in irradiated cells overall; however, the frequency was decreased as the concentration of apigenin increased, suggesting a radioprotective effect. These findings provide a basis for additional studies to help clarify the potential use and benefit of apigenin as a radioprotector.

NASA Discipline Radiation Health↗