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NASA NTRS2003

Bayesian estimation of dose thresholds

An example is described of Bayesian estimation of radiation absorbed dose thresholds (subsequently simply referred to as dose thresholds) using a specific parametric model applied to a data set on mice exposed to 60Co gamma rays and fission neutrons. A Weibull based relative risk model with a dose threshold parameter was used to analyse, as an example, lung cancer mortality and determine the posterior density for the threshold dose after single exposures to 60Co gamma rays or fission neutrons from the JANUS reactor at Argonne National Laboratory. The data consisted of survival, censoring times and cause of death information for male B6CF1 unexposed and exposed mice. The 60Co gamma whole-body doses for the two exposed groups were 0.86 and 1.37 Gy. The neutron whole-body doses were 0.19 and 0.38 Gy. Marginal posterior densities for the dose thresholds for neutron and gamma radiation were calculated with numerical integration and found to have quite different shapes. The density of the threshold for 60Co is unimodal with a mode at about 0.50 Gy. The threshold density for fission neutrons declines monotonically from a maximum value at zero with increasing doses. The posterior densities for all other parameters were similar for the two radiation types.

NASA Discipline Radiation Health↗

NASA NTRS1996

Latency and activation in the control of TGF-beta

The biological activity of the transforming growth factor-beta's (TGF-beta)3 is tightly controlled by their persistence in the extracellular compartment as latent complexes. Each of the three mammalian isoform genes encodes a product that is cleaved intracellularly to form two polypeptides, each of which dimerizes. Mature TGF-beta, a 24 kD homodimer, is noncovalently associated with the 80 kD latency-associated peptide (LAP). LAP is a fundamental component of TGF-beta that is required for its efficient secretion, prevents it from binding to ubiquitous cell surface receptors, and maintains its availability in a large extracellular reservoir that is readily accessed by activation. This latent TGF-beta complex (LTGF-beta) is secreted by all cells and is abundant both in circulating forms and bound to the extracellular matrix. Activation describes the collective events leading to the release of TGF-beta. Despite the importance of TGF-beta regulation of growth and differentiation in physiological and malignant tissue processes, remarkably little is known about the mechanisms of activation in situ. Recent studies of irradiated mammary gland reveal certain features of TGF-beta 1 activation that may shed light on its regulation and potential roles in the normal and neoplastic mammary gland.

Non-NASA Center↗

NASA NTRS1998

Effects of exposure to different types of radiation on behaviors mediated by peripheral or central systems

The effects of exposure to ionizing radiation on behavior may result from effects on peripheral or on central systems. For behavioral endpoints that are mediated by peripheral systems (e.g., radiation-induced conditioned taste aversion or vomiting), the behavioral effects of exposure to heavy particles (56Fe, 600 MeV/n) are qualitatively similar to the effects of exposure to gamma radiation (60Co) and to fission spectrum neutrons. For these endpoints, the only differences between the different types of radiation are in terms of relative behavioral effectiveness. For behavioral endpoints that are mediated by central systems (e.g., amphetamine-induced taste aversion learning), the effects of exposure to 56Fe particles are not seen following exposure to lower LET gamma rays or fission spectrum neutrons. These results indicate that the effects of exposure to heavy particles on behavioral endpoints cannot necessarily be extrapolated from studies using gamma rays, but require the use of heavy particles.

NASA Discipline Radiation Health↗

NASA NTRS1990

Radiolysis of aqueous solutions of acetic acid in the presence of Na-montmorillonite

The gamma-irradiation of 0.8 mol dm-3 aqueous, oxygen-free acetic acid solutions was investigated in the presence or absence of Na-montmorillonite. H2, CH4, CO, CO2, and several polycarboxylic acids were formed in all systems. The primary characteristics observed in the latter system were: (1) Higher yield of the decomposition of acetic acid; (2) Lower yield of the formation of polycarboxylic acids; (3) No effect on the formation of methane; (4) Higher yield of the formation of carbon dioxide; and (5) The reduction of Fe3+ in the octahedral sites of Na-montmorillonite. A possible reaction scheme was proposed to account for the observed changes. The results are important in understanding heterogeneous processes in radiation catalysis and might be significant to prebiotic chemistry.

Non-NASA Center↗

NASA NTRS2001

Relative effectiveness of HZE iron-56 particles for the induction of cytogenetic damage in vivo

One of the risks of prolonged manned space flight is the exposure of astronauts to radiation from galactic cosmic rays, which contain heavy ions such as (56)Fe. To study the effects of such exposures, experiments were conducted at the Brookhaven National Laboratory by exposing Wistar rats to high-mass, high-Z, high-energy (HZE) particles using the Alternating Gradient Synchrotron (AGS). The biological effectiveness of (56)Fe ions (1000 MeV/nucleon) relative to low-LET gamma rays and high-LET alpha particles for the induction of chromosome damage and micronuclei was determined. The mitotic index and the frequency of chromosome aberrations were evaluated in bone marrow cells, and the frequency of micronuclei was measured in cells isolated from the trachea and the deep lung. A marked delay in the entry of cells into mitosis was induced in the bone marrow cells that decreased as a function of time after the exposure. The frequencies of chromatid aberrations and micronuclei increased as linear functions of dose. The frequency of chromosome aberrations induced by HZE particles was about 3.2 times higher than that observed after exposure to (60)Co gamma rays. The frequency of micronuclei in rat lung fibroblasts, lung epithelial cells, and tracheal epithelial cells increased linearly, with slopes of 7 x 10(-4), 12 x 10(-4), and 11 x 10(-4) micronuclei/binucleated cell cGy(-1), respectively. When genetic damage induced by radiation from (56)Fe ions was compared to that from exposure to (60)Co gamma rays, (56)Fe-ion radiation was between 0.9 and 3.3 times more effective than (60)Co gamma rays. However, the HZE-particle exposures were only 10-20% as effective as radon in producing micronuclei in either deep lung or tracheal epithelial cells. Using microdosimetric techniques, we estimated that 32 cells were hit by delta rays for each cell that was traversed by the primary HZE (56)Fe particle. These calculations and the observed low relative effectiveness of the exposure to HZE particles suggest that at least part of the cytogenetic damage measured was caused by the delta rays. Much of the energy deposited by the primary HZE particles may result in cell killing and may therefore be "wasted" as far as production of detectable micronuclei is concerned. The role of wasted energy in studies of cancer induction may be important in risk estimates for exposure to HZE particles.

Non-NASA Center↗

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↗

DOE OSTI2026

Improvements to In-Canal Assay of High Specific Activity 60Co at the ATR

Improvements to the quality of measurements in the assaying of High Specific Activity (HSA) cobalt 60 produced at the Advanced Test Reactor at the Idaho National Laboratory are presented. Such assays are conducted regularly between cycles at the ATR, and due to the radiological safety concerns, they are performed within the ATR canal. A standard ion chamber detector was placed in a collimated assay tube within the canal. Another tube, parallel to the detector, was used to position various cobalt 60 standards and targets. The collimated port between these tubes allows for the targets to be pulled across via a winch system. Previous measurements were performed at discrete 1.5-inch steps using a hand-cranked winch system. Charge was collected and integrated for 10 seconds at each discrete step during a scan. Two substantial improvements to the assay include an electronically controlled, motor-driven winch system and a software controlled continuous charge collection. Combined, these changes improved the quality of measurements as well as streamline the assay process. Further examination of these charge profiles indicated a reasonable amount of photon scattering, or shine, before a line-of-sight is established. This created inaccuracies in the reported activity of the cobalt targets. A series of MCNP-6.3 calculations were performed in an effort to quantify and correct for this shine effect. The results of the calculations and how they were employed to a create shine correction factor for the in-canal cobalt assay at the ATR are presented. The overall bias showed an overestimation of the HSA cobalt 60 activity by around 7-8%.

07 - ISOTOPES AND RADIATION SOURCES↗

DOE OSTI2025

Radioisotope production at the advanced test reactor: process and lessons learned

The mission of the Advanced Test Reactor (ATR) at Idaho National Laboratory (INL) focuses on creating irradiation facilities for nuclear materials and fuels research. While radioisotope production is not a core part of the ATR mission, it is important for providing a U.S. domestic source of critical radioisotopes such as cobalt-60 (Co-60). Here, this paper gives an overview for radioisotopes currently being produced in ATR as well as other potential radioisotopes that can be produced in ATR. It also provides guidance on radioisotope production that can be applied to other test reactors.

ATR↗