Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “BIOLOGICAL EFFECT”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5
All sourcesNASA NTRSDOE OSTI
NASA NTRS2008

High- and low-LET Radiation-induced Chromosome Aberrations in Human Epithelial Cells Cultured in 3-dimensional Matrices

Energetic heavy ions pose a great health risk to astronauts who participate in extended ISS missions and will be an even greater concern for future manned lunar and Mars missions. High-LET heavy ions are particularly effective in causing various biological effects, including cell inactivation, genetic mutations, cataracts and cancer induction. Most of these biological endpoints are closely related to chromosomal damage, which can be utilized as a biomarker for radiation insults. Previously, we had studied low- and high-LET radiation-induced chromosome aberrations in human epithelial cells cultured in 2-dimension (2D) using the multicolor banding fluorescence in situ hybridization (mBAND) technique. However, it has been realized that the biological response to radiation insult in a 2D in vitro cellular environment can differ significantly from the response in 3-dimension (3D) or at the actual tissue level. In this study, we cultured human epithelial cells in 3D to provide a more suitable model for human tissue. Human mammary epithelial cells (CH184B5F5/M10) were grown in Matrigel to form 3D structures, and exposed to Fe-ions at NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory or 137Cs-gamma radiation source at the University of Texas MD Anderson Cancer Center. After exposure, cells were allowed to repair for 16hr before dissociation and subcultured at low density in 2D. G2 and metaphase chromosomes in the first cell cycle were collected in the first cell cycle after irradiation using a chemical-induced premature chromosome condensation (PCC) technique, and chromosome aberrations were analyzed using mBAND technique. With this technique, individually painted chromosomal bands on one chromosome allowed the identification of interchromosomal aberrations (translocation to unpainted chromosomes) and intrachromosomal aberrations (inversions and deletions within a single painted chromosome). Our data indicate a significant difference in the chromosome aberration yield between 2D and 3D cell cultures after gamma exposures, but not after Fe ion exposures. Therefore, the Relative Biological Effect (RBE) for induction of chromosome aberrations obtained in a 2D model may not accurately represent RBE values obtained for tissue exposure.

Hada, M.↗
NASA NTRS1989

High-energy radiation background in space

The radiation environment of near-earth space and its effects on biological and hardware systems are examined in reviews and reports. Sections are devoted to particle interactions and propagation, data bases, instrument background and dosimetry, detectors and experimental progress, biological effects, and future needs and strategies. Particular attention is given to angular distributions and spectra of geomagnetically trapped protons in LEO, bremsstrahlung production by electrons, nucleon-interaction data bases for background estimates, instrumental and atmospheric background lines observed by the SMM gamma-ray spectrometer, the GRAD high-altitude balloon flight over Antarctica, space protons and brain tumors, a new radioprotective antioxidative agent, LEO radiation measurements on the Space Station, and particle-background effects on the Hubble Space Telescope and the Lyman FUV Spectroscopic Explorer.

Rester, A. C., Jr.↗
NASA NTRS1994

Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts

The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 micrometer2 and 0.09 to 5.56 x 10(-3) micrometer2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(-5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

NASA Center JSC↗
NASA NTRS1984

Neoplastic cell transformation by energetic heavy ions and its modification with chemical agents

One of the major deleterious late effects of ionizing radiation is related to the induction of neoplasms. In the present report recent experimental results on neoplastic cell transformation by heavy ions are presented, and possible means to circumvent the carcinogenic effect of space radiation are discussed. Biological effects observed in experiments involving the use of energetic heavy ions accelerated at the Bevalac suggest that many of the biological effects observed in earlier space flight experiments may be due to space radiation, particularly cosmic rays. It is found that the effect of radiation on cell transformation is dose-rate dependent. The frequency of neoplastic transformation for a given dose decreases with a decrease of dose rate of Co-60 gamma rays. It is found that various chemical agents give radiation protection, including DMSO.

Yang, T. C.↗
NASA NTRS2002

Genomic instability and bystander effects: a paradigm shift in radiation biology?

A basic paradigm in radiobiology is that, following exposure to ionizing radiation, the deposition of energy in the cell nucleus and the resulting damage to DNA, the principal target, are responsible for the radiation's deleterious biological effects. Findings in two rapidly expanding fields of research--radiation-induced genomic instability and bystander effects--have caused us to reevaluate these central tenets. In this article, the potential influence of induced genomic instability and bystander effects on cellular injury after exposure to low-level radiation will be reviewed.

NASA Discipline Radiation Health↗
NASA NTRS1992

An analysis of particle track effects on solid mammalian tissues

Relative biological effectiveness (RBE) and quality factor (Q) at extreme values of linear energy transfer (LET) have been determined on the basis of experiments with single-cell systems and specific tissue responses. In typical single-cell systems, each heavy particle (Ar or Fe) passes through a single cell or no cell. In experiments on animal tissues, however, each heavy particle passes through several cells, and the LET can exceed 200 keV micrometers-1 in every cell. In most laboratory animal tissue systems, however, only a small portion of the hit cells are capable of expressing the end-point being measured, such as cell killing, mutation or carcinogenesis. The following question was therefore addressed: do RBEs and Q factors derived from single-cell experiments properly account for the damage at high LET when multiple cells are hit by HZE tracks? A review is offered in which measured radiation effects and known tissue properties are combined to estimate on the one hand, the number of cells at risk, p3n, per track, where n is the number of cells per track based on tissue and organ geometry, and p3 is the probability that a cell in the track is capable of expressing the experimental end-point. On the other hand, the tissue and single-cell responses are compared by determining the ratio RBE in tissue/RBE in corresponding single cells. Experimental data from the literature indicate that tissue RBEs at very high LET (Fe and Ar ions) are higher than corresponding single-cell RBEs, especially in tissues in which p3n is high.

Non-NASA Center↗
NASA NTRS2005

Evaluation of Late Effects of Heavy-Ion Radiation on Mesenchymal Stem Cells

The overall objective of this recently funded study is to utilize well-characterized model test systems to assess the impact of pluripotent stem cell differentiation on biological effects associated with high-energy charged particle radiation. These stem cells, specifically mesenchymal stem cells (MSCs), have the potential for differentiation into bone, cartilage, fat, tendons, and other tissue types. The characterization of the regulation mechanisms of MSC differentiation to the osteoblastic lineage by transcription factors, such as Runx2/Cbfa1 and Osterix, and osteoinductive proteins such as members of the bone morphogenic protein family are well established. More importantly, for late biological effects, MSCs have been shown to contribute to tissue restructuring and repair after tissue injury. The complex regulation of and interactions between inflammation and repair determine the eventual outcome of the responses to tissue injury, for which MSCs play a crucial role. Additionally, MSCs have been shown to respond to reactive oxygen species, a secondary effector of radiation, by differentiating. With this, we hypothesized that differentiation of MSCs can alter or exacerbate the damage initiated by radiation, which can ultimately lead to late biological effects of misrepair/fibrosis which may ultimately lead to carcinogenesis. Currently, studies are underway to examine high-energy X-ray radiation at low and high doses, approximately 20 and 200 Rad, respectively, on cytogenetic damage and gene modulation of isolated MSCs. These cells, positive for MSC surface markers, were obtained from three persons. In vitro cell samples were harvested during cellular proliferation and after both cellular recovery and differentiation. Future work will use established in vitro models of increasing complexity to examine the value of traditional 2D tissue-culture techniques, and utilize 3D in vitro tissue culture techniques that can better assess late effects associated with radiation.

Gonda, S.R.↗
NASA NTRS1994

Charged-particle mutagenesis 2. Mutagenic effects of high energy charged particles in normal human fibroblasts

The biological effects of high Linear Energy Transfer (LET) charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/micrometer to 975 KeV/micrometer with particle energy (on the cells) between 94-603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/micrometer. The inactivation cross-section (alpha i) and the action cross-section for mutant induction (alpha m) ranged from 2.2 to 92.0 sq micrometer and 0.09 to 5.56 x 10(exp -3) sq micrometer respectively. The maximum values were obtained by Fe-56 with an LET of 200 keV/micrometer. The mutagenicity (alpha m/alpha i) ranged from 2.05 to 7.99 x 10(exp -5) with the maximum value at 150 keV/micrometer. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

Chen, D. J.↗
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 NTRS1992

Commentary 2 to Cox and Little: radiation-induced oncogenic transformation: the interplay between dose, dose protraction, and radiation quality

There is now a substantial body of evidence for end points such as oncogenic transformation in vitro, and carcinogenesis and life shortening in vivo, suggesting that dose protraction leads to an increase in effectiveness relative to a single, acute exposure--at least for radiations of medium linear energy transfer (LET) such as neutrons. Table I contains a summary of the pertinent data from studies in which the effect is seen. [table: see text] This phenomenon has come to be known as the "inverse dose rate effect," because it is in marked contrast to the situation at low LET, where protraction in delivery of a dose of radiation, either by fractionation or low dose rate, results in a decreased biological effect; additionally, at medium and high LET, for radiobiological end points such as clonogenic survival, the biological effectiveness is independent of protraction. The quantity and quality of the published reports on the "inverse dose rate effect" leaves little doubt that the effect is real, but the available evidence indicates that the magnitude of the effect is due to a complex interplay between dose, dose rate, and radiation quality. Here, we first summarize the available data on the inverse dose rate effect and suggest that it follows a consistent pattern in regard to dose, dose rate, and radiation quality; second, we describe a model that predicts these features; and, finally, we describe the significance of the effect for radiation protection.

Review, Tutorial↗
NASA NTRS2001

Genomic instability, bystander effect, cytoplasmic irradiation and other phenomena that may achieve fame without fortune

The possible risk of induced malignancies in astronauts, as a consequence of the radiation environment in space, is a factor of concern for long term missions. Cancer risk estimates for high doses of low LET radiation are available from the epidemiological studies of the A-bomb survivors. Cancer risks at lower doses cannot be detected in epidemiological studies and must be inferred by extrapolation from the high dose risks. The standard setting bodies, such as the ICRP recommend a linear, no-threshold extrapolation of risks from high to low doses, but this is controversial. A study of mechanisms of carcinogenesis may shed some light on the validity of a linear extrapolation. The multi-step nature of carcinogenesis suggests that the role of radiation may be to induce a mutation leading to a mutator phenotype. High energy Fe ions, such as those encountered in space are highly effective in inducing genomic instability. Experiments involving the single particle microbeam have demonstrated a "bystander effect", ie a biological effect in cells not themselves hit, but in close proximity to those that are, as well as the induction of mutations in cells where only the cytoplasm, and not the nucleus, have been traversed by a charged particle. These recent experiments cast doubt on the validity of a simple linear extrapolation, but the data are so far fragmentary and conflicting. More studies are necessary. While mechanistic studies cannot replace epidemiology as a source of quantitative risk estimates, they may shed some light on the shape of the dose response relationship and therefore on the limitations of a linear extrapolation to low doses.

NASA Discipline Radiation Health↗
NASA NTRS2024

DNA Break Clustering as a Predictor of Cell Death across Various Radiation Qualities: Influence of Cell Size, Cell Asymmetry, and Beam Orientation

Cosmic radiation, composed of high charge and energy (HZE) particles, causes cellular DNA damage that can result in cell death or mutation that can evolve into cancer. In this work, a cell death model is applied to several cell lines exposed to HZE ions spanning a broad range of linear energy transfer (LET) values. We hypothesize that chromatin movement leads to the clustering of multiple double strand breaks (DSB) within one radiation-induced foci (RIF). The survival probability of a cell population is determined by averaging the survival probabilities of individual cells, which is function of the number of pairwise DSB interactions within RIF. The simulation code RITCARD was used to compute DSB. Two clustering approaches were applied to determine the number of RIF per cell. RITCARD outputs were combined with experimental data from four normal human cell lines to derive the model parameters and expand its predictions in response to ions with LET ranging from ∼0.2keV/μmto∼3000keV/μm. Spherical and ellipsoidal nuclear shapes and two ion beam orientations were modeled to assess the impact of geometrical properties on cell death. The calculated average number of RIF per cell reproduces the saturation trend for high doses and high-LET values that is usually experimentally observed. The cell survival model generates the recognizable bell shape of LET dependence for the relative biological effectiveness (RBE). At low LET, smaller nuclei have lower survival due to increased DNA density and DSB clustering. At high LET, nuclei with a smaller irradiation area either because of a smaller size or a change in beam orientation have a higher survival rate due to a change in the distribution of DSB/RIF per cell. If confirmed experimentally, the geometric characteristics of cells would become a significant factor in predicting radiation-induced biological effects.

cell survival↗
NASA NTRS2001

Optimized shielding for space radiation protection

Future deep space mission and International Space Station exposures will be dominated by the high-charge and -energy (HZE) ions of the Galactic Cosmic Rays (GCR). A few mammalian systems have been extensively tested over a broad range of ion types and energies. For example, C3H10T1/2 cells, V79 cells, and Harderian gland tumors have been described by various track-structure dependent response models. The attenuation of GCR induced biological effects depends strongly on the biological endpoint, response model used, and material composition. Optimization of space shielding is then driven by the nature of the response model and the transmission characteristics of the given material.

NASA Discipline Radiation Health↗
NASA NTRS1981

Effects on biological systems of reflected light from a satellite power system

Light reflection produced by the satellite power system and the possible effects of that light on the human eye, plants, and animals were studied. For the human eye, two cases of reflected light, might cause eye damage if viewed for too long. These cases are: (1) if, while in low Earth orbit, the orbital transfer vehicle is misaligned to reflect the Sun to Earth there exists a maximum safe fixation time for the naked eye of 42.4 secs; (2) reflection from the aluminum paint on the back of the orbital transfer vehicle, while in or near low Earth orbit, can be safely viewed by the naked eye for 129 sec. For plants and animals the intensity and timing of light are not a major problem. Ways for reducing and/or eliminating the irradiances are proposed.

White, M.↗
NASA NTRS1993

Spaceflight Radiation Health program at the Lyndon B. Johnson Space Center

The Johnson Space Center leads the research and development activities that address the health effects of space radiation exposure to astronaut crews. Increased knowledge of the composition of the environment and of the biological effects of space radiation is required to assess health risks to astronaut crews. The activities at the Johnson Space Center range from quantification of astronaut exposures to fundamental research into the biological effects resulting from exposure to high energy particle radiation. The Spaceflight Radiation Health Program seeks to balance the requirements for operational flexibility with the requirement to minimize crew radiation exposures. The components of the space radiation environment are characterized. Current and future radiation monitoring instrumentation is described. Radiation health risk activities are described for current Shuttle operations and for research development program activities to shape future analysis of health risk.

Johnson, A. Steve↗
NASA NTRS2011

A Hypothesis on Biological Protection from Space Radiation Through the Use of New Therapeutic Gases as Medical Counter Measures

Exposure to astronauts could be a significant obstacle for long duration manned space exploration because of current uncertainties regarding the extent of biological effects. Furthermore, concepts for protective shielding also pose a technically challenging issue due to the nature of cosmic radiation and current mass and power constraints with modern exploration technology. As biological damage from exposure is associated with increased oxidative stress, it would be enabling to mitigate and/or prevent stress prior to the development of clinical symptoms and disease. This paper hypothesizes a "systems biology" approach in which a combination of chemical and biological mitigation techniques are used conjunctively. It proposes using new, therapeutic, medical gases as both chemical radioprotectors for radical scavenging and biological promoters for management of the body s response to exposure. From reviewing radiochemistry of water, biological effects of CO, H2, NO, and H2S gas, and mechanisms of radiation biology, it is concluded that this approach may have great therapeutic potential for exposure. Furthermore, it also appears to have potential for curtailing the pathogenesis of other diseases in which oxidative stress has been implicated including cardiovascular disease, cancer, chronic inflammatory disease, hypertension, ischemia/reperfusion injury, acute respiratory distress syndrome, Parkinson s and Alzheimer s disease, cataracts, and aging.

Schoenfeld, Michael P.↗