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NASA NTRS2002

Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

NASA Discipline Radiation Health↗

NASA NTRS1976

Ames collaborative study of cosmic ray neutrons

The results of a collaborative study to define both the neutron flux and the spectrum more precisely and to develop a dosimetry package that can be flown quickly to altitude for solar flare events are described. Instrumentation and analysis techniques were used which were developed to measure accelerator-produced radiation. The instruments were flown in the Ames Research Center high altitude aircraft. Neutron instrumentation consisted of Bonner spheres with both active and passive detector elements, threshold detectors of both prompt-counter and activation-element types, a liquid scintillation spectrometer based on pulse-shape discrimination, and a moderated BF3 counter neutron monitor. In addition, charged particles were measured with a Reuter-Stokes ionization chamber system and dose equivalent with another instrument. Preliminary results from the first series of flights at 12.5 km (41,000 ft) are presented, including estimates of total neutron flux intensity and spectral shape and of the variation of intensity with altitude and geomagnetic latitude.

Hewitt, J. E.↗

NASA NTRS2016

Evidence Report: Risk of Radiation Carcinogenesis

As noted by Durante and Cucinotta (2008), cancer risk caused by exposure to space radiation is now generally considered a main hindrance to interplanetary travel for the following reasons: large uncertainties are associated with the projected cancer risk estimates; no simple and effective countermeasures are available, and significant uncertainties prevent scientists from determining the effectiveness of countermeasures. Optimizing operational parameters such as the length of space missions, crew selection for age and sex, or applying mitigation measures such as radiation shielding or use of biological countermeasures can be used to reduce risk, but these procedures have inherent limitations and are clouded by uncertainties. Space radiation is comprised of high energy protons, neutrons and high charge (Z) and energy (E) nuclei (HZE). The ionization patterns and resulting biological insults of these particles in molecules, cells, and tissues are distinct from typical terrestrial radiation, which is largely X-rays and gamma-rays, and generally characterized as low linear energy transfer (LET) radiation. Galactic cosmic rays (GCR) are comprised mostly of highly energetic protons with a small component of high charge and energy (HZE) nuclei. Prominent HZE nuclei include He, C, O, Ne, Mg, Si, and Fe. GCR ions have median energies near 1 GeV/n, and energies as high as 10 GeV/n make important contributions to the total exposure. Ionizing radiation is a well known carcinogen on Earth (BEIR 2006). The risks of cancer from X-rays and gamma-rays have been established at doses above 50 mSv (5 rem), although there are important uncertainties and on-going scientific debate about cancer risk at lower doses and at low dose rates (<50 mSv/h). The relationship between the early biological effects of HZE nuclei and the probability of cancer in humans is poorly understood, and it is this missing knowledge that leads to significant uncertainties in projecting cancer risks during space exploration (Cucinotta and Durante 2006; Durante and Cucinotta 2008).

Huff, Janice↗

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

Proton Damage Effects in Linear Integrated Circuts

Proton testing of linear circuits has identified devices where significantly more damage occurs at equivalent total dose levels with protons than tests with gamma rays.

lateral pnp transistors proton damage effects line↗

NASA NTRS1995

Dosimetry on STS-42 with the RME APD

Beginning with the STS-42 mission, this laboratory began participating in instrument comparison studies in which space radiation was measured contiguously by passive and active methods. The active instrument was the RME-3 microdosimeter. This instrument measures four-channel LET spectra and employs a tissue-equivalent proportional counter. It is sensitive to the full LET range of ionizing radiation present. Our area passive dosimeter, the RME APD, contained arrays of plastic nuclear track detectors (PNTD's) and thermoluminescent detectors (TLD's). The PNTD's measure LET spectra, while the TLD's measure total absorbed dose. The object of this experiment is to compare the active and passive measurements on the basis of LET spectra, total absorbed dose, and dose equivalent. The STS-42 mission was launched on January 22, 1992, with a flight duration of 8.052 days. The orbit had an inclination of 57 deg and an altitude of 302 km. The shuttle in this orbit is expected to encounter radiation levels dominated by galactic cosmic rays (GCR's) with a lesser contribution from trapped protons in the lower region of the South Atlantic Anomaly (SAA).

Source record↗

NASA NTRS2006

Testing and Qualifying Linear Integrated Circuits for Radiation Degradation in Space

This paper discusses mechanisms and circuit-related factors that affect the degradation of linear integrated circuits from radiation in space. For some circuits there is sufficient degradation to affect performance at total dose levels below 4 krad(Si) because the circuit design techniques require higher gain for the pnp transistors that are the most sensitive to radiation. Qualification methods are recommended that include displacement damage as well as ionization damage.

integrated circuit testing↗

NASA NTRS1995

Fault Tolerant Characteristics of Artificial Neural Network Electronic Hardware

The fault tolerant characteristics of analog-VLSI artificial neural network (with 32 neurons and 532 synapses) chips are studied by exposing them to high energy electrons, high energy protons, and gamma ionizing radiations under biased and unbiased conditions. The biased chips became nonfunctional after receiving a cumulative dose of less than 20 krads, while the unbiased chips only started to show degradation with a cumulative dose of over 100 krads. As the total radiation dose increased, all the components demonstrated graceful degradation. The analog sigmoidal function of the neuron became steeper (increase in gain), current leakage from the synapses progressively shifted the sigmoidal curve, and the digital memory of the synapses and the memory addressing circuits began to gradually fail. From these radiation experiments, we can learn how to modify certain designs of the neural network electronic hardware without using radiation-hardening techniques to increase its reliability and fault tolerance.

Artificial Neural Network↗

NASA NTRS1978

Hyperthermia in the treatment of cancer: A review of the radiobiological basis

Temperatures in the range 41.5 C to 43.5 C tend to be more damaging to malignant than nonmalignant cells. Where local hyperthermia (41.5 C to 43.5 C) is combined with ionizing radiation, a significant therapeutic ratio may be realized. Total body hyperthermia, alone or combined with other therapeutic modalities, can provide palliation for some systemic malignancies but may not be as effective as local hyperthermia for treating local disease. The influence of hyperthermia on immune mechanisms and the risk of metastatic spread of potential tumor growth stimulation need further investigation. Among other questions needing elucidation before hyperthermia can be considered a standard treatment modality are the time-dose (for heating) relationships to produce an optimal therapeutic ratio and whether the late sequela of combined heat and ionizing radiation may result in an unacceptable risk of patient morbidity.

Baker, D. G.↗

NASA NTRS1995

Ionizing radiation measurements on LDEF: A0015 Free flyer biostack experiment

This report covers the analysis of passive radiation detectors flown as part of the A0015 Free Flyer Biostack on LDEF (Long Duration Exposure Facility). LET (linear energy transfer) spectra and track density measurements were made with CR-39 and Polycarbonate plastic nuclear track detectors. Measurements of total absorbed dose were carried out using Thermoluminescent Detectors. Thermal and resonance neutron dose equivalents were measured with LiF/CR-39 detectors. High energy neutron and proton dose equivalents were measured with fission foil/CR-39 detectors.

Benton, E. V.↗

NASA NTRS1996

Clusters of DNA damage induced by ionizing radiation: formation of short DNA fragments. II. Experimental detection

The basic 30-nm chromatin fiber in the mammalian cell consists of an unknown (possibly helical) arrangement of nucleosomes, with about 1.2 kb of DNA per 10-nm length of fiber. Track-structure considerations suggest that interactions of single delta rays or high-LET particles with the chromatin fiber might result in the formation of multiple lesions spread over a few kilobases of DNA (see the accompanying paper: W.R. Holley and A. Chatterjee, Radiat. Res. 145, 188-199, 1996). In particular, multiple DNA double-strand breaks and single-strand breaks may form. To test this experimentally, primary human fibroblasts were labeled with [3H]thymidine and exposed at 0 degrees C to X rays or accelerated nitrogen or iron ions in the LET range of 97-440 keV/microns. DNA was isolated inside agarose plugs and subjected to agarose gel electrophoresis under conditions that allowed good separation of 0.1-2 kb size DNA. The bulk of DNA remained in the well or migrated only a small distance into the gel. It was found that DNA fragments in the expected size range were formed linearly with dose with an efficiency that increased with LET. A comparison of the yield of such fragments with the yield of total DNA double-strand breaks suggests that for the high-LET ions a substantial proportion (20-90%) of DNA double-strand breaks are accompanied within 0.1-2 kb by at least one additional DNA double-strand break. It is shown that these results are in good agreement with theoretical calculations based on treating the 30-nm chromatin fiber as the target for ionizing particles. Theoretical considerations also predict that the clusters will contain numerous single-strand breaks and base damages. It is proposed that such clusters be designated "regionally multiply damaged sites." Postirradiation incubation at 37 degrees C resulted in a decline in the number of short DNA fragments, suggesting a repair activity. The biological significance of regionally multiply damaged sites is presently unknown.

Non-NASA Center↗

NASA NTRSDate not supplied

Comparison of the NAIRAS Trajectory Dose Model With ISS Measurements: Effects of Trapped Particles and Solar Energetic Particle Events.

The NAIRAS(Nowcast of Aerospace Ionizing RAdiation system) model was initially developed for fast computation of GCR and SEP events in the Earth's atmosphere. It was recently improved for computing the effects of trapped particles and its domain of validity was extended to the near space environments, which notably includes the international space station (ISS). To validate the new capabilities of the model, we compared its outputs with some measurements made in the ISS. Historical data contained several SEP events while newer measurements made with the ARMAS instrument flying in the experience bay of KIBO show the influence of trapped particles and GCR over the total dose received.

Guillaume Gronoff↗

NASA NTRS2002

Predictions for Radiation Shielding Materials

Radiation from galactic cosmic rays (GCR) and solar particle events (SPE) is a serious hazard to humans and electronic instruments during space travel, particularly on prolonged missions outside the Earth s magnetic fields. Galactic cosmic radiation (GCR) is composed of approx. 98% nucleons and approx. 2% electrons and positrons. Although cosmic ray heavy ions are 1-2% of the fluence, these energetic heavy nuclei (HZE) contribute 50% of the long-term dose. These unusually high specific ionizations pose a significant health hazard acting as carcinogens and also causing microelectronics damage inside spacecraft and high-flying aircraft. These HZE ions are of concern for radiation protection and radiation shielding technology, because gross rearrangements and mutations and deletions in DNA are expected. Calculations have shown that HZE particles have a strong preference for interaction with light nuclei. The best shield for this radiation would be liquid hydrogen, which is totally impractical. For this reason, hydrogen-containing polymers make the most effective practical shields. Shielding is required during missions in Earth orbit and possibly for frequent flying at high altitude because of the broad GCR spectrum and during a passage into deep space and LunarMars habitation because of the protracted exposure encountered on a long space mission. An additional hazard comes from solar particle events (SPEs) which are mostly energetic protons that can produce heavy ion secondaries as well as neutrons in materials. These events occur at unpredictable times and can deliver a potentially lethal dose within several hours to an unshielded human. Radiation protection for humans requires safety in short-term missions and maintaining career exposure limits within acceptable levels on future long-term exploration missions. The selection of shield materials can alter the protection of humans by an order of magnitude. If improperly selected, shielding materials can actually increase radiation damage due to penetration properties and nuclear fragmentation. Protecting space-borne microelectronics from single event upsets (SEUs) by transmitted radiation will benefit system reliability and system design cost by using optimal shield materials. Long-term missions on the surface of the Moon or Mars will require the construction of habitats to protect humans during their stay. One approach to the construction is to make structural materials from lunar or Martian regolith using a polymeric material as a binder. The hydrogen-containing polymers are considerably more effective for radiation protection than the regolith, but the combination minimizes the amount of polymer to be transported. We have made composites of simulated lunar regolith with two different polymers, LaRC-SI, a high-performance polyimide thermoset, and polyethylene, a thermoplastic.

Kiefer, Richard L.↗

NASA NTRS1990

Ionizing program environment at the Mars surface

The Langley cosmic ray transport code and the Langley nucleon transport code are used to quantify the transport and attenuation of galactic cosmic rays and solar proton flares through the Martian atmosphere. Surface doses are estimated using both a low-density and a high-density carbon dioxide model of the atmosphere which, in the vertical direction, provide a total of 16 g/sq cm and 22 g/sq cm of protection, respectively. At the Mars surface during the solar minimum cycle, a blood-forming organ (BFO) dose-equivalent of 10.5 to 12 rem/yr due to galactic cosmic ray transport and attenuation is calculated. Estimates of the BFO dose-equivalents which would have been incurred at the surface from three large solar flare events are also calculated. Doses are also estimated at altitudes up to 12 km above the Martian surface where the atmosphere will provide less total protection.

Simonsen, Lisa C.↗

NASA NTRS1992

Radiation exposure predictions for long-duration-stay Mars missions

In this study, the ionizing radiation environment is estimated, using the Mission Radiation Calculation (MIRACAL) program, for several long-duration-stay Mars missions proposed for early in the 21st century. Both long-fast and minimum energy transfer missions are evaluated, and their 30-day maximum, annual maximum, and total slab skin and blood-forming organ (BFO) doses are compared. When large flares were included while the astronauts were on the surface, the delivered dose did not significantly contribute to the total dose (less than 4 cSv BFO dose, or 8 percent of the guideline annual limit, for the most energetic event simulated) due to the substantial protection provided by the Martian atmosphere. However, dose delivered by large flares during transit is dependent on vehicle shielding and distance from the sun. All of the long-fast transfer missions studied had lower total and annual maximum doses than the corresponding minimum energy transfer missions (on average, 30 percent less for missions having no large flares and the shielding thicknesses evaluated in this study). For all the missions studied, having the astronauts spend one-third of their day during transit in a 10 g/sq cm storm shelter resulted in significantly lower total doses.

Striepe, Scott A.↗

NASA NTRS2020

Proton Radiation Effects on HgCdTe Avalanche Photodiode Detectors

Space radiation damage and proton induced transient effects were evaluated on 4.4 μm cutoff HgCdTe avalanche photodiode (APD) arrays developed by Leonardo DRS. Device performances as a function of total dose up to 100 krad (Si) were measured with ~60 MeV protons on 3 types of APD samples: 4x4 pixel APD fanout arrays with and without connection to a read-out integrated circuit (ROIC), and a 2x8 pixel photon counting APD focal plane array (FPA). A gamma-ray test was also conducted to study ionization effects. Both APD arrays exhibited a small decrease in the quantum efficiency and a linear increase in the dark current with the proton fluence. The 2x8 pixel photon counting FPA also exhibited an increase in the dark count rate with proton dose. After the proton irradiation and an overnight room temperature warm-up, the APD dark currents at 80 K increased significantly in both types of APD arrays. All radiation damage to these HgCdTe APD arrays annealed out after baking them at >85 °C for several hours. Transient protons through the devices were found to cause large pulses at the detector output but recover within 1 μs.

Xiaoli Sun↗

NASA NTRS1995

Effect Of Clock Mode On Radiation Hardness Of An ADC

Report discusses techniques for testing and evaluating effects of total dosages of ionizing radiation on performances of high-resolution successive-approximation analog-to-digital converters (ADCs), without having to test each individual bit or transition. Reduces cost of testing by reducing tests to few critical parametric measurements, from which one determines approximate radiation failure levels providing good approximations of responses of converters for purpose of total-dose-radiation evaluations.

Lee, Choon I.↗

NASA NTRS2018

Potential Dietary Countermeasure Against Spaceflight-Induced Bone Loss

As humans venture further into space and beyond low Earth orbit, space radiation is one of the main challenges for astronauts' health. Radiation-induced bone loss is a potential health problem for long duration habitation in space. We showed that a dietary countermeasure prevents bone loss in mice exposed to total body irradiation (TBI). We used a range of ionizing radiation, gamma (137Cs), proton (1H), iron (56Fe), and a combination of sequential proton and iron beam (1H/56Fe/1H) to evaluate skeletal responses. These TBI cover a range of linear energy transfer (LET), from low-LET such as proton, to high-LET such as 56Fe (HZE: high Z- high energy) at doses between 1-2 Gy. The countermeasure diet, composed of 25% Dried Plum (DP) was effective at preventing radiation-induced cancellous bone loss in appendicular bone (tibia). Furthermore, exposing mice to HZE radiation, such as 56Fe (1Gy), impaired ex vivo growth of marrow-derived, bone-forming osteoblasts, which led to reduced mineralization capacity (-77%). In contrast, mice fed the DP diet did not display these deficits, showing the diet's capacity to protect marrow-derived osteoprogenitors. Dietary DP prevented the increase of bone resorbing osteoclast cells, inflammation and oxidative stress, while protecting the osteoprogenitors and mesenchymal stem cells, which few drugs against osteoporosis may achieve. Spaceflight is a combination of multiple factors including microgravity, in addition to space radiation. Therefore, we conducted additional studies to determine if the DP diet could prevent simulated spaceflight (simulated microgravity and radiation combined) bone loss. Mice were exposed to gamma (TBI, 137Cs, 2 Gy), simulated microgravity (using the hindlimb unloading system, HU) or TBI+HU. While we observed bone loss in mice fed the control diet (CD) due to both treatments (TBI=14%, HU=20%), and a worse effect with combined treatments (TBI+HU=25%), mice fed the DP diet did not sustain significant bone loss relative to untreated controls. The DP diet prevented microarchitectural decrements in both appendicular bone (tibia) and axial bone (vertebrae). In addition, the DP diet mitigated HU-induced deficits in osteoblastogenesis. Interestingly, lower doses of DP diet (5%, 10%) did not appear to prevent cancellous bone loss, which shows the importance of identifying the active component(s) of DP. Finally, we have preliminary data showing the potential of DP to prevent radiation-induced damage at a systematic level.. In summary, this novel dietary countermeasure is a promising candidate nutritional countermeasure for spaceflight-induced bone loss and tissue damage.

Countermeasure↗