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Results for “Dose-Response Relationship, Radiation”

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NASA NTRS1994

A computational approach to the relationship between radiation induced double strand breaks and translocations

A theoretical framework is presented which provides a quantitative analysis of radiation induced translocations between the ab1 oncogene on CH9q34 and a breakpoint cluster region, bcr, on CH 22q11. Such translocations are associated frequently with chronic myelogenous leukemia. The theory is based on the assumption that incorrect or unfaithful rejoining of initial double strand breaks produced concurrently within the 200 kbp intron region upstream of the second abl exon, and the 16.5 kbp region between bcr exon 2 and exon 6 interact with each other, resulting in a fusion gene. for an x-ray dose of 100 Gy, there is good agreement between the theoretical estimate and the one available experimental result. The theory has been extended to provide dose response curves for these types of translocations. These curves are quadratic at low doses and become linear at high doses.

NASA Discipline Radiation Health↗

NASA NTRS1997

Latent transforming growth factor beta1 activation in situ: quantitative and functional evidence after low-dose gamma-irradiation

The biological activity of transforming growth factor beta1 (TGF-beta) is controlled by its secretion as a latent complex in which it is noncovalently associated with latency-associated peptide (LAP). Activation is the extracellular process in which TGF-beta is released from LAP, and is considered to be a primary regulatory control. We recently reported rapid and persistent changes in TGF-beta immunoreactivity in conjunction with extracellular matrix remodeling in gamma-irradiated mouse mammary gland. Our hypothesis is that these specific changes in immunoreactivity are indicative of latent TGF-beta activation. In the present study, we determined the radiation dose response and tested whether a functional relationship exists between radiation-induced TGF-beta and collagen type III remodeling. After radiation exposures as low as 0.1 Gy, we detected increased TGF-beta immunoreactivity in the mammary epithelium concomitant with decreased LAP immunostaining, which are events consistent with activation. Quantitative image analysis demonstrated a significant (P=0.0005) response at 0.1 Gy without an apparent threshold and a linear dose response to 5 Gy. However, in the adipose stroma, loss of LAP demonstrated a qualitative threshold at 0.5 Gy. Loss of LAP paralleled induction of collagen III immunoreactivity in this tissue compartment. We tested whether TGF-beta mediates collagen III expression by treating animals with TGF-beta panspecific monoclonal antibody, 1D11.16, administered i.p. shortly before irradiation. Radiation-induced collagen III staining in the adipose stroma was blocked in an antibody dose-dependent manner, which persisted through 7 days postirradiation. RNase protection assay revealed that radiation-induced elevation of total gland collagen III mRNA was also blocked by neutralizing antibody treatment. These data provide functional confirmation of the hypothesis that radiation exposure leads to latent TGF-beta activation, support our interpretation of the reciprocal shift in immunoreactivity as evidence of activation, and implicate TGF-beta as a mediator of tissue response to ionizing radiation. The sensitivity of activation to low radiation doses points to a potential role for TGF-beta in orchestrating tissue response to oxidative stress. As such, radiation may be useful as a probe to delineate the consequences of latent TGF-beta activation in situ.

NASA Discipline Radiation Health↗

NASA NTRS1998

Analysis of mutant quantity and quality in human-hamster hybrid AL and AL-179 cells exposed to 137Cs-gamma or HZE-Fe ions

We measured the number of mutants and the kinds of mutations induced by 137Cs-gamma and by HZE-Fe (56Fe [600 MeV/amu, LET = 190 KeV/micrometer) in standard AL human hamster hybrid cells and in a new variant hybrid, AL-179. We found that HZE-Fe was more mutagenic than 137Cs-gamma per unit dose (about 1.6 fold), but was slightly less mutagenic per mean lethal dose, DO, at both the S1 and hprt- loci of AL cells. On the other hand, HZE-Fe induced about nine fold more complex S1- mutants than 137Cs-gamma rays, 28% vs 3%. 137Cs-gamma rays induced about twice as many S1- mutants and hprt-mutants in AL-179 as in AL cells, and about nine times more of the former were complex, and potentially unstable kinds of mutations.

NASA Discipline Radiation Health↗

NASA NTRS1992

Radiobiological studies with the nematode Caenorhabditis elegans. Genetic and developmental effects of high LET radiation

The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long-duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets. There are many consequences of this feature to biological endpoints when compared with effects of ionizing photons. Dose vs response and dose-rate kinetics may be modified, DNA and cellular repair systems may be altered in their abilities to cope with damage, and the qualitative features of damage may be unique for different ions. The nematode Caenorhabditis elegans is being used to address these and related questions associated with exposure to radiation. HZE-induced mutation, chromosome aberration, cell inactivation and altered organogenesis are discussed along with plans for radiobiological experiments in space.

short duration↗

NASA NTRS1989

Effects of incandescent radiation on photosynthesis, growth rate and yield of 'Waldmann's Green' leaf lettuce

Effects of different ratios incandescent (ln) to fluorescent (Fl) radiation were tested on growth of 'Waldmann's Green' leaf lettuce (Lactuca sativa L.) in a controlled environment. After 4 days of treatment, dry weight, leaf area, relative growth rate (RGR), net assimilation rate (NAR), leaf area ratio (LAR) and photosynthetic rate (Pn) were greater for plants grown at 84 rather than 16% of total irradiance (82 W m-2) from ln lamps. Although leaf dry weight and area were 12-17% greater at 84% ln after the first 8 days of treatment, there were no differences in RGR or Pn between treatments during the last 4 days. If 84% ln was compared with 50% ln, all cumulative growth parameters, RGR, NAR and Pn were greater for 84% ln during the first 4 days of treatment. However, during the second 4 days, RGR was greater for the 50% ln treatment, resulting in no net difference in leaf dry weight or area between treatments. Shifting from 84 to 50% ln radiation between the first and second 4 days of treatment increased plant dry weight, leaf area, RGR and NAR relative to those under 84% ln for 8 days continuously.

NASA Program CELSS↗

NASA NTRS1985

Reduced phenylalanine ammonia-lyase and tyrosine ammonia-lyase activities and lignin synthesis in wheat grown under low pressure sodium lamps

Wheat (Triticum aestivum L. cv Fremont) grown in hydroponic culture under 24-hour continuous irradiation at 560 to 580 micromoles per square meter per second from either metalhalide (MH), high pressure sodium (HPS), or low pressure sodium (LPS) lamps reached maturity in 70 days. Grain yields were similar under all three lamps, although LPS-grown plants lodged at maturity. Phenylalanine ammonia-lyase (PAL) and a tyrosine ammonia lyase (TAL) with lesser activity were detected in all extracts of leaf, inflorescence, and stem. Ammonia-lyase activities increased with age of the plant, and plants grown under the LPS lamp displayed PAL and TAL activities lower than wheat cultured under MH and HPS radiation. Greenhouse solar-grown wheat had the highest PAL and TAL activities. Lignin content of LPS-grown wheat was also significantly reduced from that of plants grown under MH or HPS lamps or in the greenhouse, showing a correlation with the reduced PAL and TAL activities. Ratios of far red-absorbing phytochrome to total phytochrome were similar for all three lamps, but the data do not yet warrant a conclusion about specific wavelengths missing from the LPS lamps that might have induced PAL and TAL activities in plants under the other lamps.

Triticum/enzymology/growth & development/metabolis↗

NASA NTRS1997

Environmental modification of yield and nutrient composition of 'Waldmann's Green' leaf lettuce

Leaf number, dry weight, and nutrient composition of Lactuca sativa L. cv. Waldmann's Green leaves were compared following 9 days of treatment in a controlled environment room under various combinations of photosynthetic photon flux (PPF:350 vs 800 micromoles m-2 s-1), atmospheric CO2 level (ambient vs 1500 micromoles mol-1), and single-strength (1X:15 mM) vs double-strength (2X:30 mM) nitrogen (N) as NO3- alone or as NH4(+) + NO3- (1:5 molar ratio). CO2 enrichment greatly enhanced leaf number under all PPF and N conditions, but increased leaf dry weight only at high PPF. Conditions favoring high photosynthesis enhanced leaf starch content 3-fold, and protein content increased as much as 64% with 2X NH4(+)+NO3-. Free sugar content was 6 to 9% of leaf dry weight for all treatment combinations, while fat was 1.5 to 3.5%. Ash content varied from 15 to 20% of leaf dry weight. Modified controlled environments can be used to enhance the nutritional content as well as the yield of crops to be used for life support in space-deployed, self-sustaining human habitats. Leaf lettuce is a useful model crop for demonstrating the potential of nutritional value added by environmental manipulation.

Non-NASA Center↗

NASA NTRS1988

Modeling the effects of light, carbon dioxide, and temperature on the growth of potato

This study examined the effects of light, temperature and carbon dioxide on the growth of potato (Solanum tuberosum L.) in a controlled environment in order to ascertain the best growing conditions for potato in life support systems in space. 'Norland' and 'Russet Burbank' were grown in 6-L pots of peat-vermiculite for 56 d in growth chambers at the University of Wisconsin Biotron. Environmental factor levels included continuous light (24-h photoperiod) at 250, 400, and 550 micromoles m-2 s-1 PPF; constant temperature at 16, 20, and 24 degrees C; and CO2 at approximately 400, 1000, and 1600 microliters L-1. Separate effects analysis and ridge analysis provided a means to examine the effects of individual environmental factors and to determine combinations of factors that are expected to give the best increases in yields over the central design point. The response surface of Norland indicated that tuber yields were highest with moderately low temperature (18.7 degrees C), low CO2 (400 microliters L-1) and high light (550 micromoles m-2 s-1 PPF). These conditions also favored shorter stem growth. Russet Burbank tuber yields were highest at moderately low temperature (17.5 degrees C), high CO2 (1600 microliters L-1) and medium analyses will be used to project the most efficient conditions for growth of potatoes in closed ecological life support systems (CELSS) in space colonies.

NASA Discipline Life Support Systems↗

NASA NTRS1996

Photosynthetic photon flux, photoperiod, and temperature effects on emissions of (Z)-3-hexenal, (Z)-3-hexenol, and (Z)-3-hexenyl acetate from lettuce

To investigate the effects of environment on plant volatile emissions, 'Waldmann's Green' leaf lettuce was cultivated under different levels of photosynthetic photon flux (PPF), photoperiod, and temperature. A modified growth chamber was used to sample plant volatile emissions nondestructively, over time, and under controlled conditions. Total volatile emission rates were significantly higher from lettuce cultivated under PPF of 360 or 200 micromoles m-2 s-1 compared to 105 micromoles m-2 s-1, and significantly higher under a 16-h photoperiod than an 8-h photoperiod. No differences were detected among emission rates from different temperature treatments. In controlled environments, emissions could be regulated by adjusting environmental conditions accordingly.

NASA Program Advanced Life Support↗

NASA NTRS1987

Enhancement of phototropic response to a range of light doses in Triticum aestivum coleoptiles in clinostat-simulated microgravity

The phototropic dose-response relationship has been determined for Triticum aestivum cv. Broom coleoptiles growing on a purpose-built clinostat apparatus providing gravity compensation by rotation about a horizontal axis at 2 rev min-1. These data are compared with data sets obtained with the clinostat axis vertical and stationary, as a 1 g control, and rotating vertically to examine clinostat effects other than gravity compensation. Triticum at 1 g follows the well-established pattern of other cereal coleoptiles with a first positive curvature at low doses, followed by an indifferent response region, and a second positive response at progressively increasing doses. However, these response regions lie at higher dose levels than reported for Avena. There is no significant difference between the responses observed with the clinostat axis vertical in the rotating and stationary modes, but gravity compensation by horizontal rotation increases the magnitude of first and second positive curvatures some threefold at 100 min after stimulation. The indifferent response is replaced by a significant curvature towards the light source, but remains apparent as a reduced curvature response at these dose levels.

Non-NASA Center↗

NASA NTRS1986

Growth and tuberization of potato (Solanum tuberosum L.) under continuous light

The growth and tuberization of potatoes (Solanum tuberosum L.) maintained for 6 weeks under four different regimes of continuous irradiance were compared to plants given 12 hours light and 12 hours dark. Treatments included: (a) continuous photosynthetic photon flux of 200 micromoles per square meter per second cool-white fluorescent (CWF); (b) continuous 400 micromoles per square meter per second CWF; (c) 12 hours 400 micromoles per square meter per second CWF plus 12 hours dim CWF at 5 micromoles per square meter per second; (d) 12 hours [400] micromoles per square meter per second CWF plus 12 hours dim incandescent (INC) at 5 micromoles per square meter per second and a control treatment of 12 hours light at 400 micromoles per square meter per second CWF and 12 hours dark. The study included five cultivars ranging from early- to late-season types: 'Norland,' 'Superior,''Norchip,' 'Russet Burbank,' and 'Kennebec,' Tuber development progressed well under continuous irradiation at 400 micromoles per square meter per second and under 12 hours irradiance and 12 hours dark, while tuber development was suppressed in all other light treatments. Continuous irradiation at 200 or 400 micromoles per square meter per second resulted in severe stunting and leaf malformation on 'Superior' and 'Kennebec' plants, but little or no injury and vigorous shoot growth in the other cultivars. No injury or stunting were apparent under 12-dim light or 12-dark treatments. Plants given 12 hours dim INC showed significantly greater stem elongation but less total biomass than plants in other treatments. The continuous light encouraged shoot growth over tuber growth but this trend was overridden by providing a high irradiance level. The variation among cultivars for tolerance to continuous lighting indicates that potato may be a useful species for photoinhibition studies.

NASA Program CELSS↗

NASA NTRS1990

A common fluence threshold for first positive and second positive phototropism in Arabidopsis thaliana

The relationship between the amount of light and the amount of response for any photobiological process can be based on the number of incident quanta per unit time (fluence rate-response) or on the number of incident quanta during a given period of irradiation (fluence-response). Fluence-response and fluence rate-response relationships have been measured for second positive phototropism by seedlings of Arabidopsis thaliana. The fluence-response relationships exhibit a single limiting threshold at about 0.01 micromole per square meter when measured at fluence rates from 2.4 x 10(-5) to 6.5 x 10(-3) micromoles per square meter per second. The threshold values in the fluence rate-response curves decrease with increasing time of irradiation, but show a common fluence threshold at about 0.01 micromole per square meter. These thresholds are the same as the threshold of about 0.01 micromole per square meter measured for first positive phototropism. Based on these data, it is suggested that second positive curvature has a threshold in time of about 10 minutes. Moreover, if the times of irradiation exceed the time threshold, there is a single limiting fluence threshold at about 0.01 micromole per square meter. Thus, the limiting fluence threshold for second positive phototropism is the same as the fluence threshold for first positive phototropism. Based on these data, we suggest that this common fluence threshold for first positive and second positive phototropism is set by a single photoreceptor pigment system.

NASA Discipline Number 29-20↗

NASA NTRS1988

Evidence for involvement of phytochrome in tumor development on plants

The regulation of nonpathogenic tumorous growths on tomato plants by red and far-red radiation was studied using leaf discs floated on water and irradiated from beneath. It was found that red light (600-700 nanometers) was required for the induction of tumors on tomato (Lycopersicon hirsutum Humb. & Bonpl. Plant Introduction LA 1625), while both blue (400-500 nanometers) and green (500-600 nanometers) light had little effect on tumor development. Detailed studies with red light demonstrated that tumor development increased with increasing photon flux and duration, though duration was the more significant factor. It was observed that tumor development could be prevented by the addition of far-red irradiance to red irradiance or by providing far-red irradiance immediately following red irradiance. The effectiveness of red and far-red irradiance in the regulation of tumor development indicates phytochrome involvement in this response. These findings should provide additional insight into the multiplicity of physiological factors regulating the development of nonpathogenic tumorous growths in plants.

Non-NASA Center↗

NASA NTRS1995

Root-shoot interaction in the greening of wheat seedlings grown under red light

Wheat seedlings grown with roots exposed to constant red light (300-500 micromoles m-2 s-1) did not accumulate chlorophyll in the leaves. In contrast, seedlings grown with their roots shielded from light accumulated chlorophylls. Chlorophyll biosynthesis could be induced in red-light-grown chlorophyll-deficient yellow plants by either reducing the red-light intensity at the root surface to 100 micromoles m-1 s-1 or supplementing with 6% blue light. The inhibition of chlorophyll biosynthesis was due to impairment of the Mg-chelatase enzyme working at the origin of the Mg-tetrapyrrole pathway. The root-perceived photomorphogenic inhibition of shoot greening demonstrates root-shoot interaction in the greening process.

NASA Center KSC↗

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 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↗