Search NASA⌕ Search

SEARCH · Search NASA

Results for “RADIOSENSITIVITY”

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 55 records · Page 3

Factors modifying the response of large animals to low-intensity radiation exposure

In assessing the biological response to space radiation, two of the most important modifying factors are dose protraction and dose distribution to the body. Studies are reported in which sheep and swine were used to compare the hematology and lethality response resulting from radiation exposure encountered in a variety of forms, including acute (high dose-rate), chronic (low dose-rate), combinations of acute and chronic, and whether received as a continuous or as fractionated exposure. While sheep and swine are basically similar in response to acute radiation, their sensitivity to chronic irradiation is markedly different. Sheep remain relatively sensitive as the radiation exposure is protracted while swine are more resistant and capable of surviving extremely large doses of chronic irradiation. This response to chronic irradiation correlated well with changes in radiosensitivity and recovery following an acute, sublethal exposure.

Page, N. P.↗

Preliminary calculation of solar cosmic ray dose to the female breast in space mission

No regulatory dose limits are specifically assigned for the radiation exposure of female breasts during manned space flight. However, the relatively high radiosensitivity of the glandular tissue of the breasts and its potential exposure to solar flare protons on short- and long-term missions mandate a priori estimation of the associated risks. A model for estimating exposure within the breast is developed for use in future NASA missions. The female breast and torso geometry is represented by a simple interim model. A recently developed proton dose-buildup procedure is used for estimating doses. The model considers geomagnetic shielding, magnetic-storm conditions, spacecraft shielding, and body self-shielding. Inputs to the model include proton energy spectra, spacecraft orbital parameters, STS orbiter-shielding distribution at a given position, and a single parameter allowing for variation in breast size.

Shavers, Mark↗

Preliminary analysis of a radiobiological experiment for LifeSat

With the possibility of performing radiation life science experiments on a dedicated satellite (LifeSat) in space, a combined effort in radiation physics and radiation dosimetry, in addition to radiation biology, is clearly required to ensure that meaningful biological experiments can be performed. To better understand the relationship of these disciplines, some possible LifeSat missions are examined. As a trial biological system, tumorigenesis is considered in the Harderian gland of mice, a system of sufficient radiosensitivity for which relative biological effectiveness (RBE) is well defined by laboratory experiments.

Wilson, John W.↗

Cellular changes in microgravity and the design of space radiation experiments

Cell metabolism, secretion and cell-cell interactions can be altered during space flight. Early radiobiology experiments have demonstrated synergistic effects of radiation and microgravity as indicated by increased mutagenesis, increased chromosome aberrations, inhibited development, and retarded growth. Microgravity-induced changes in immune cell functions include reduced blastogenesis and cell-mediated, delayed-type hypersensitivity responses, increased cytokine secretions, but inhibited cytotoxic effects an macrophage differentiation. These effects are important because of the high radiosensitivity of immune cells. It is difficult to compare ground studies with space radiation biology experiments because of the complexity of the space radiation environment, types of radiation damage and repair mechanisms. Altered intracellular functions and molecular mechanisms must be considered in the design and interpretation of space radiation experiments. Critical steps in radiocarcinogenesis could be affected. New cell systems and hardware are needed to determine the biological effectiveness of the low dose rate, isotropic, multispectral space radiation and the potential usefulness of radioprotectants during space flight.

Morrison, D. R.↗

Chromosomal damage observed in first postirradiation metaphases of repair-proficient and -deficient cell lines

Investigation of radiation induced damage in mutant strains of mammalian cells which show a defect in the rejoining of DNA double strand breaks provides an unique opportunity to examine the role of double strand breaks and the mechanisms of double strand break rejoining in the production of chromosome aberrations. This is particularly important, because there is increasing evidence that the DNA double strand break is the major lesion responsible for the formation of chromosome aberrations. To address this issue, we studied the induction of chromosome aberrations in xrs-5 cells, an x-ray sensitive strain of a Chinese hamster ovary cell line, which shows a defect in the rejoining of double strand breaks and their wild-type parent CHO-cells. Because radiosensitivity depends strongly on cellular age, the experiments were performed with synchronous cells.

Ritter, S.↗

Solar particle dose rate buildup and distribution in critical body organs

Human body organs have varying degrees of radiosensitivity as evidenced by radioepidemiologic tables. The major critical organs for both the male and female that have been identified include the lung, thyroid, stomach, and breast (female). Using computerized anatomical models of the 50th percentile United States Air Force male and female, we present the self-shielding effects of these various body organs and how the shielding effects change as the location (dose point) in the body varies. Several major solar proton events from previous solar cycles and several events from the current 22nd solar cycle have been analyzed. The solar particle event rise time, peak intensity, and decay time vary considerably from event to event. Absorbed dose and dose equivalent rate calculations and organ risk assessment data are presented for each critical body organ. These data are compared with the current NASA astronaut dose limits as recommended by the National Council on Radiation Protection and Measurements.

Atwell, William↗

Introduction to Radiation Issues for International Space Station Extravehicular Activities

The International Space Station (ISS) provides significant challenges for radiation protection of the crew due to a combination of circumstances including: the extended duration of missions for many crewmembers, the exceptionally dynamic nature of the radiation environment in ISS orbit, and the necessity for numerous planned extravehicular activities (EVA) for station construction and maintenance. Radiation protection requires accurate radiation dose measurements and precise risk modeling of the transmission of high fluxes of energetic electrons and protons through the relatively thin shielding provided by the space suits worn during EVA. Experiments and analyses have been performed due to the necessity to assure complete radiation safety for the EVA crew and thereby ensure mission success. The detailed characterization described of the material and topological properties of the ISS space suits can be used as a basis for design of space suits used in future exploration missions. In radiation protection practices, risk from exposure to ionizing radiation is determined analytically by the level of exposure, the detrimental quality of the radiation field, the inherent radiosensitivity of the tissues or organs irradiated, and the age and gender of the person at the time of exposure. During low Earth orbit (LEO) EVA, the relatively high fluxes of low-energy electrons and protons lead to large variations in exposure of the skin, lens of the eye, and tissues in other shallow anatomical locations. The technical papers in this publication describe a number of ground-based experiments that precisely measure the thickness of the NASA extravehicular mobility unit (EMU) and Russian Zvezda Orlan-M suits using medical computerized tomography (CT) X-ray analysis, and particle accelerator experiments that measure the minimum kinetic energy required by electrons and photons to penetrate major components of the suits. These studies provide information necessary for improving the understanding of the current ISS space suits and provide insights into improved approaches for the design of future suits. This chapter begins with a summary of the dynamic ionizing radiation environment in LEO space and introduces the concepts and quantities used to quantify exposure to space radiation in LEO. The space suits used for EVA and the experimental partial human phantom are described. Subsequent chapters report results from measured charged particle fields before and after incident protons and secondary particles are transported through the space suits and into organs and tissues.

Shavers, M. R.↗

Radiation Exposure Analysis for ISS: The Female Astronaut in EVA

Special exposure limit recommendations have been designated by the NCRP for US. astronauts in LEO operations. These have been established from consideration of a 3% lifetime excess risk of cancer mortality for a 10-yr. active career. The most recent recommendations of the NCRP have incorporated modified procedures for evaluating exposures with accompanying adjustments in career limits. Of special importance are the limit specifications for female exposures, which are approximately 40% less than those for males. Furthermore, radiosensitive organs unique to females require additional attention.

Anderson, Brooke M.↗

Astronaut Exposures to Ionizing Radiation in a Lightly-Shielded Spacesuit

The normal working and living areas of the astronauts are designed to provide an acceptable level of protection against the hazards of ionizing radiation of the space environment. Still there are occasions when they must don a spacesuit designed mainly for environmental control and mobility and leave the confines of their better-protected domain. This is especially true for deep space exploration. The impact of spacesuit construction on the exposure of critical astronaut organs will be examined in the ionizing radiation environments of free space, the lunar surface and the Martian surface. The computerized anatomical male model is used to evaluate astronaut self-shielding factors and to determine space radiation exposures to critical radiosensitive human organs.

Wilson, J. W.↗

An overactivated ATR/CHK1 pathway is responsible for the prolonged G2 accumulation in irradiated AT cells

Induction of checkpoint responses in G1, S, and G2 phases of the cell cycle after exposure of cells to ionizing radiation (IR) is essential for maintaining genomic integrity. Ataxia telangiectasia mutated (ATM) plays a key role in initiating this response in all three phases of the cell cycle. However, cells lacking functional ATM exhibit a prolonged G2 arrest after IR, suggesting regulation by an ATM-independent checkpoint response. The mechanism for this ataxia telangiectasia (AT)-independent G2-checkpoint response remains unknown. We report here that the G2 checkpoint in irradiated human AT cells derives from an overactivation of the ATR/CHK1 pathway. Chk1 small interfering RNA abolishes the IR-induced prolonged G2 checkpoint and radiosensitizes AT cells to killing. These results link the activation of ATR/CHK1 with the prolonged G2 arrest in AT cells and show that activation of this G2 checkpoint contributes to the survival of AT cells.

NASA Discipline Radiation Health↗

Response of thyroid follicular cells to gamma irradiation compared to proton irradiation: II. The role of connexin 32

The objective of this study was to determine whether connexin 32-type gap junctions contribute to the "contact effect" in follicular thyrocytes and whether the response is influenced by radiation quality. Our previous studies demonstrated that early-passage follicular cultures of Fischer rat thyroid cells express functional connexin 32 gap junctions, with later-passage cultures expressing a truncated nonfunctional form of the protein. This model allowed us to assess the role of connexin 32 in radiation responsiveness without relying solely on chemical manipulation of gap junctions. The survival curves generated after gamma irradiation revealed that early-passage follicular cultures had significantly lower values of alpha (0.04 Gy(-1)) than later-passage cultures (0.11 Gy(-1)) (P < 0.0001, n = 12). As an additional way to determine whether connexin 32 was contributing to the difference in survival, cultures were treated with heptanol, resulting in higher alpha values, with early-passage cultures (0.10 Gy(-1)) nearly equivalent to untreated late-passage cultures (0.11 Gy(-1)) (P > 0.1, n = 9). This strongly suggests that the presence of functional connexin 32-type gap junctions was contributing to radiation resistance in gamma-irradiated thyroid follicles. Survival curves from proton-irradiated cultures had alpha values that were not significantly different whether cells expressed functional connexin 32 (0.10 Gy(-1)), did not express connexin 32 (0.09 Gy(-1)), or were down-regulated (early-passage plus heptanol, 0.09 Gy(-1); late-passage plus heptanol, 0.12 Gy(-1)) (P > 0.1, n = 19). Thus, for proton irradiation, the presence of connexin 32-type gap junctional channels did not influence their radiosensitivity. Collectively, the data support the following conclusions. (1) The lower alpha values from the gamma-ray survival curves of the early-passage cultures suggest greater repair efficiency and/or enhanced resistance to radiation-induced damage, coincident with the expression of connexin 32-type gap junctions. (2) The increased sensitivity of FRTL-5 cells to proton irradiation was independent of their ability to communicate through connexin 32 gap junctions. (3) The fact that the beta components of the survival curves from both gamma rays and proton beams were similar (average 0.022 +/- 0.008 Gy(-2), P > 0.1, n = 39) suggests that at higher doses the loss of viability occurs at a relatively constant rate and is independent of radiation quality and the presence of functional gap junctions.

Non-NASA Center↗

New measurements for hadrontherapy and space radiation: biology

The dual goals of optimizing clinical efficacy of hadrontherapy and determining radiation risk estimates for space research have intersected to a common focus for investigation of the biological effects of charged particles. This paper briefly highlights recent international progress at accelerator facilities engaged in both biological and clinical studies of the effects of particle beams, primarily protons, carbon and iron ions. Basic mechanisms of molecular, cellular and tissue responses continue under investigation for radiations with a range of ionization densities. Late normal tissue effects, including the risk of cancer in particular, are of importance for both research fields. International cooperation has enhanced the rate of progress as evidenced by recent publications. Specific areas of biomedical research related to the biological radiotoxicity of critical organs (especially the central nervous system), individual radiosensitivities to radiation carcinogenesis, and the analysis of effects in mixed radiation fields still require more research. Recommendations for addressing these issues are made.

Review↗

Chromosome aberrations in the blood lymphocytes of astronauts after space flight

Cytogenetic analysis of the lymphocytes of astronauts provides a direct measurement of space radiation damage in vivo, which takes into account individual radiosensitivity and considers the influence of microgravity and other stress conditions. Chromosome exchanges were measured in the blood lymphocytes of eight crew members after their respective space missions, using fluorescence in situ hybridization (FISH) with chromosome painting probes. Significant increases in aberrations were observed after the long-duration missions. The in vivo dose was derived from the frequencies of translocations and total exchanges using calibration curves determined before flight, and the RBE was estimated by comparison with individually measured physical absorbed doses. The values for average RBE were compared to the average quality factor (Q) from direct measurements of the lineal energy spectra using a tissue-equivalent proportional counter (TEPC) and radiation transport codes. The ratio of aberrations identified as complex was slightly higher after flight, which is thought to be an indication of exposure to high-LET radiation. To determine whether the frequency of complex aberrations measured in metaphase spreads after exposure to high-LET radiation was influenced by a cell cycle delay, chromosome damage was analyzed in prematurely condensed chromosome samples collected from two crew members before and after a short-duration mission. The frequency of complex exchanges after flight was higher in prematurely condensed chromosomes than in metaphase cells for one crew member.

NASA Center JSC↗

An initiation-promotion model of tumour prevalence from high-charge and energy radiations

A repair/misrepair kinetic model for multiple radiation-induced lesions (mutation inactivation) is coupled to a two-mutation model of initiation-promotion in tissue to provide a parametric description of tumour prevalence in the mouse Harderian gland from high-energy and charge radiations. Track-structure effects are considered using an action-cross section model. Dose-response curves are described for gamma rays and relativistic ions, and good agreement with experiment is found. The effects of nuclear fragmentation are also considered for high-energy proton and alpha-particle exposures. The model described provides a parametric description of age-dependent cancer induction for a wide range of radiation fields. Radiosensitivity parameters found in the model for an initiation mutation (sigma 0 = 7.6 x 10(-10) cm2 and D0 = 148.0 Gy) are somewhat different than previously observed for neoplastic transformation of C3H10T1/2 cell cultures (sigma 0 = 0.7 x 10(-10) cm2 and D0 = 117.0 Gy). We consider the two hypotheses that radiation acts solely as an initiator or as both initiator and promoter and make model calculations for fractionation exposures from gamma rays and relativistic Fe ions. For fractionated Fe exposures, an inverse-dose-rate effect is provided by a promotion hypothesis with an increase of 30% or more, dependent on the dose level and fractionation schedule, using a mutation rate for promotion similar to that of single-gene mutations.

NASA Discipline Radiation Health↗

Experimental models for cellular radiation targets: LET, RBE and radioprotectors

The topics of this presentation are: a brief review of the early research, the ideas it stimulated and the ways they are used in current efforts to explain cellular radiosensitivity; an analysis of the strengths and weaknesses of two experimental models used in vitro for simulating the induction of double strand breaks (DSB) and single strand breaks (SSB) in situ. Note that when alkali is used to denature cellular DNA for the determination of strand breaks, both overt SSB and the SSB that result from DSB in the denaturation process are recorded as total strand breaks (TSB). All information is taken from published literature.

NASA Discipline Number 93-10↗

Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice

Ataxia-telangiectasia (AT) is a genetic syndrome resulting from the inheritance of two defective copies of the ATM gene that includes among its stigmata radiosensitivity and cancer susceptibility. Epidemiological studies have demonstrated that although women with a single defective copy of ATM (AT heterozygotes) appear clinically normal, they may never the less have an increased relative risk of developing breast cancer. Whether they are at increased risk for radiation-induced breast cancer from medical exposures to ionizing radiation is unknown. We have used a murine model of AT to investigate the effect of a single defective Atm allele, the murine homologue of ATM, on the susceptibility of mammary epithelial cells to radiation-induced transformation. Here we report that mammary epithelial cells from irradiated mice with one copy of Atm truncated in the PI-3 kinase domain were susceptible to radiation-induced genomic instability and generated a 10% incidence of dysplastic mammary ducts when transplanted into syngenic recipients, whereas cells from Atm(+/+) mice were stable and formed only normal ducts. Since radiation-induced ductal dysplasia is a precursor to mammary cancer, the results indicate that AT heterozygosity increases susceptibility to radiogenic breast cancer in this murine model system.

Non-NASA Center↗

Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene

Female BALB/c mice are unusually radiosensitive and more susceptible than C57BL/6 and other tested inbred mice to ionizing radiation (IR)-induced mammary tumors. This breast cancer susceptibility is correlated with elevated susceptibility for mammary cell transformation and genomic instability following irradiation. In this study, we report the identification of two BALB/c strain-specific polymorphisms in the coding region of Prkdc, the gene encoding the DNA-dependent protein kinase catalytic subunit, which is known to be involved in DNA double-stranded break repair and post-IR signal transduction. First, we identified an A --> G transition at base 11530 resulting in a Met --> Val conversion at codon 3844 (M3844V) in the phosphatidylinositol 3-kinase domain upstream of the scid mutation (Y4046X). Second, we identified a C --> T transition at base 6418 resulting in an Arg --> Cys conversion at codon 2140 (R2140C) downstream of the putative leucine zipper domain. This unique PrkdcBALB variant gene is shown to be associated with decreased DNA-dependent protein kinase catalytic subunit activity and with increased susceptibility to IR-induced genomic instability in primary mammary epithelial cells. The data provide the first evidence that naturally arising allelic variation in a mouse DNA damage response gene may associate with IR response and breast cancer risk.

Non-NASA Center↗

A role for chromosomal instability in the development of and selection for radioresistant cell variants

Chromosome instability is a common occurrence in tumour cells. We examined the hypothesis that the elevated rate of mutation formation in unstable cells can lead to the development of clones of cells that are resistant to the cancer therapy. To test this hypothesis, we compared chromosome instability to radiation sensitivity in 30 independently isolated clones of GM10115 human-hamster hybrid cells. There was a broader distribution of radiosensitivity and a higher mean SF(2)in chromosomally unstable clones. Cytogenetic and DNA double-strand break rejoining assays suggest that sensitivity was a function of DNA repair efficiency. In the unstable population, the more radioresistant clones also had significantly lower plating efficiencies. These observations suggest that chromosome instability in GM10115 cells can lead to the development of cell variants that are more resistant to radiation. In addition, these results suggest that the process of chromosome breakage and recombination that accompanies chromosome instability might provide some selective pressure for more radioresistant variants. Copyright 2001 Cancer Research Campaign.

NASA Discipline Radiation Health↗