Biological effects of heavy ions
Biological effects of heavy ions - radiation effects in animals and man
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Biological effects of heavy ions - radiation effects in animals and man
Genetic and developmental effects of heavy ions in maize and rice were investigated. Heavy particles with various charges and energies were accelerated at the BEVALAC. The frequency of occurrence of white-yellow stripes on leaves of plants developed from irradiated maize seeds increased linearly with dose, and high Linear Energy Transfer (LET) heavy charged particles, e.g., neon, argon, and iron, were 2-12 times as effective as gamma rays in inducing this type of mutation. The effectiveness of high-LET heavy ion in (1) inhibiting rice seedling growth, (2) reducing plant fertility, (3) inducing chromosome aberration and micronuclei in root tip cells and pollen mother cells of the first generation plants developed from exposed seeds, and (4) inducing mutation in the second generation, were greater than that of low-LET gamma rays. All effects observed were dose-dependent; however, there appeared to be an optimal range of doses for inducing certain types of mutation, for example, for argon ions (400 MeV/u) at 90-100 Gy, several valuable mutant lines with favorable characters, such as semidwarf, early maturity and high yield ability, were obtained. Experimental results suggest that the potential application of heavy ions in crop improvement is promising. Restriction-fragment-length-polymorphism (RFLP) analysis of two semidwarf mutants induced by argon particles revealed that large DNA alterations might be involved in these mutants.
The present investigation is concerned with the effects of heavy-ion radiation on the vascular system and the embryonic development, taking into account the results of experiments with neonatal rats and mouse embryos. It is found that heavy ions can be highly effective in producing brain hemorrhages and in causing body deformities. Attention is given to aspects of methodology, the induction of brain hemorrhages by X-rays and heavy ions, and the effect of iron particles on embryonic development. Reported results suggest that high linear energy transfer (LET) heavy ions can be very effective in producing developmental abnormalities.
Heavy-ion radiation effects knowledge across SiC power devices is examined and insights for more rugged designs and appropriate test methods geared toward space applications are extracted. The conclusions drawn are supported by recent publicly reported heavy-ion test results of a modified SiC MOSFET design.
Ion sheaths near radiating antennas in ionosphere
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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.
Radiation quality effects are largely determined by energy deposition in small volumes of characteristic sizes less than 10 nm representative of short-segments of DNA, the DNA nucleosome, or molecules initiating oxidative stress in the nucleus, mitochondria, or extra-cellular matrix. On this scale, qualitatively distinct types of molecular damage are possible for high linear energy transfer (LET) radiation such as heavy ions compared to low LET radiation. Unique types of DNA lesions or oxidative damages are the likely outcome of the energy deposition. The frequency distribution for energy imparted to 1-20 nm targets per unit dose or particle fluence is a useful descriptor and can be evaluated as a function of impact parameter from an ions track. In this work, the simulation of 1-Gy irradiation of a cubic volume of 5 micron by: 1) 450 (1)H(+) ions, 300 MeV; 2) 10 (12)C(6+) ions, 290 MeV/amu and 3) (56)Fe(26+) ions, 1000 MeV/amu was done with the Monte-Carlo simulation code RITRACKS. Cylindrical targets are generated in the irradiated volume, with random orientation. The frequency distribution curves of the energy deposited in the targets is obtained. For small targets (i.e. <25 nm size), the probability of an ion to hit a target is very small; therefore a large number of tracks and targets as well as a large number of histories are necessary to obtain statistically significant results. This simulation is very time-consuming and is difficult to perform by using the original version of RITRACKS. Consequently, the code RITRACKS was adapted to use multiple CPU on a workstation or on a computer cluster. To validate the simulation results, similar calculations were performed using targets with fixed position and orientation, for which experimental data are available [5]. Since the probability of single- and double-strand breaks in DNA as function of energy deposited is well know, the results that were obtained can be used to estimate the yield of DSB, and can be extended to include other targeted or non-target effects.
On Moon and Mars, there will be more galactic cosmic rays and higher radiation doses than on Earth. Our experimental studies showed that heavy ion radiation can effectively cause mutation and chromosome aberrations and that high Linear Energy Transfer (LET) heavy-ion induced mutants can be irreversible. Chromosome translocations and deletions are common in cells irradiated by heavy particles, and ionizing radiations are effective in causing hyperploidy. The importance of the genetic changes in the evolution of life is an interesting question. Through evolution, there is an increase of DNA content in cells from lower forms of life to higher organisms. The DNA content, however, reached a plateau in vertebrates. By increasing DNA content, there can be an increase of information in the cell. For a given DNA content, the quality of information can be changed by rearranging the DNA. Because radiation can cause hyperploidy, an increase of DNA content in cells, and can induce DNA rearrangement, it is likely that the evolution of life on Mars will be effected by its radiation environment. A simple analysis shows that the radiation level on Mars may cause a mutation frequency comparable to that of the spontaneous mutation rate on Earth. To the extent that mutation plays a role in adaptation, radiation alone on Mars may thus provide sufficient mutation for the evolution of life.
Experimental results on ion-induced leakage current increase in 4H-SiC Schottky power diodes are presented. Monte Carlo and TCAD simulations show that degradation is due to the synergy between applied bias and ion energy deposition. This degradation is possibly related to thermal spot annealing at the metal semiconductor interface. This thermal annealing leads to an inhomogeneity of the Schottky barrier that could be responsible for the increase leakage current as a function of fluence.
In this work, we evaluated the differential effects of low- and high-LET radiation on 3-D organotypic cultures in order to investigate radiation quality impacts on gene expression and cellular responses. Current risk models for assessment of space radiation-induced cancer have large uncertainties because the models for adverse health effects following radiation exposure are founded on epidemiological analyses of human populations exposed to low-LET radiation. Reducing these uncertainties requires new knowledge on the fundamental differences in biological responses (the so-called radiation quality effects) triggered by heavy ion particle radiation versus low-LET radiation associated with Earth-based exposures. In order to better quantify these radiation quality effects in biological systems, we are utilizing novel 3-D organotypic human tissue models for space radiation research. These models hold promise for risk assessment as they provide a format for study of human cells within a realistic tissue framework, thereby bridging the gap between 2-D monolayer culture and animal models for risk extrapolation to humans. To identify biological pathway signatures unique to heavy ion particle exposure, functional gene set enrichment analysis (GSEA) was used with whole transcriptome profiling. GSEA has been used extensively as a method to garner biological information in a variety of model systems but has not been commonly used to analyze radiation effects. It is a powerful approach for assessing the functional significance of radiation quality-dependent changes from datasets where the changes are subtle but broad, and where single gene based analysis using rankings of fold-change may not reveal important biological information.
Cosmic-ray heavy ions have become a concern in space radiation effects analyses. Heavy ions rapidly deposit energy and create dense ionization trails as they traverse materials. Collection of the free charge disrupts the operation of microelectronic circuits. This effect, called the single-event upset, can cause a loss of digital data. Passage of high linear energy transfer particles through the eyes has been observed by Apollo astronauts. These heavy ions have great radiobiological effectiveness and are the primary risk factor for leukemia induction on a manned Mars mission. Models of the transport of heavy cosmic-ray nuclei through materials depend heavily on our understanding of the cosmic-ray environment, nuclear spallation cross sections, and computer transport codes. Our group has initiated and pursued the development of a full capability for modeling these transport processes. A recent review of this ongoing effort is presented in Ref. 5. In this paper, we discuss transport methods and present new results comparing the attenuation of cosmic rays in various materials.
Exposure to galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. To simulate the type of radiation exposure occurring during spaceflight, model organisms can be exposed to relevant doses via Five-Ion Galactic Cosmic Radiation Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. We have investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy. Following exposure, immune, brain and behavioral (sensorimotor, risk-taking and cognitive) measures were acquired at ‘Acute’ (IR+24hrs, IR+72hrs), ‘Intermediate’ (IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) to inform biological responses anticipated during a transit to Moon and Mars. There were pronounced sex differences observed in all outcome measurements, while very few radiation induced effects were observed. Those dose effects that were observed were primarily in cytokine expression and less so in behavioral measurements. Further studies will investigate if radiation, microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance, ultimately to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions.
Outside the magnetic field of the Earth, high energy heavy ions constitute a relevant part of the biologically significant dose to astronauts during the very long travels through space. The typical pattern of energy deposition in the matter by heavy ions on the microscopic scale is believed to produce spatially correlated damage in the DNA which is critical for radiobiological effects. We have investigated the influence of a lucite shielding on the initial production of very small DNA fragments in human fibroblasts irradiated with 1 GeV/u iron (Fe) ions. We also used gamma rays as reference radiation. Our results show: (1) a lower effect per incident ion when the shielding is used; (2) an higher DNA Double Strand Breaks (DSB) induction by Fe ions than by gamma rays in the size range 1-23 kbp; (3) a non-random DNA DSB induction by Fe ions. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.
A systematic study of the properties of various polymer pottant materials and of the electrochemical corrosion mechanisms in solar cell materials is required for advancing the technology of terrestrial photovoltaic modules. The items of specific concern in this sponsored research activity involve: (1) kinetics of plasticizer loss in PVB, (2) kinetics of water absorption and desorption in PVB, (3) kinetics of water absorption and desorption in EVA, (4) the electrical properties at PVB as a function of temperature and humidity, (5) the electrical properties of EVA as a function of temperature and humidity, (6) solar cell corrosion characteristics, (7) water absorption effects in PVB and EVA, and (8) ion implantation and radiation effects in PVB and EVA.
Heavy-ion radiation can result in silicon carbide power device degradation and/or catastrophic failure. Test procedures and data interpretation must consider the impact that heavy-ion induced off-state leakage current increases will have on subsequent single-event effect susceptibility and testability. On orbit, reliable performance in the presence of increased off-state leakage currents due to cumulative ion-induced non-catastrophic single-event effects must be assured over the mission lifetime. This work presents a large body of heavy-ion test data for different diode, power MOSFET, and JFET devices. Susceptibility to single-event effects is compared between SiC and Si power devices. Initial recommendations on heavy-ion radiation test methods for silicon carbide power devices are made and radiation hardness assurance is discussed with the goal of moving one step closer to reliably getting this technology off the ground into a broad array of spacecraft and instruments that will benefit from its unique capabilities.
While it is common knowledge that electromagnetic radiation such as x-rays and gamma rays affect physical-chemical characteristics (PC) of compounds in addition to their toxic and mutagenic effects on biological systems, there are no reports on the effects of cosmic radiation encountered during space missions on stability of pharmaceuticals. Alterations in PC of drug formulations can adversely affect treatment with medications in space. Preliminary evaluation of stability and shelf-life of select pharmaceuticals (12) flown on space missions revealed that 37% and 40% of the formulations failed to meet USP requirements after shuttle and ISS flights, respectively. Based on these results, the current investigation is designed to examine the effect of proton (P) and heavy ion (Fe) radiation on 20 pharmaceutical preparations flown aboard the shuttle and ISS. The objectives of this project are: 1) Examine susceptibility of pharmaceuticals to short acute bouts of high intensity ionizing radiation species encountered during space flights; 2) Estimate extent of degradation of susceptible formulations as a function of intensity of each beam (P & Fe); and 3) compare and contrast the effects of single beam irradiation to that of a combined beam (P + Fe) that simulates space craft environment on drug stability. Irradiations were conducted at the Brookhaven National Laboratories (BNL) with beam strengths of 10 cGy, 10 or 50Gy of P and Fe beams separately. Preliminary evaluation of results revealed a reduction in the chemical content of label claim ranging 12-55 % for Augmentin, 7% for promethzine tablets and 9% for ciprofloxacin ointment. These results are in agreement, although less in magnitude than those observed during space flight and after gamma irradiation.
A general overview on the space environment and its effects on materials is presented. The topics include: 1) Impact of Space Effects on Spacecraft Costs; 2) Space Environment Effects on Spacecraft by Source; 3) Primary Source of Space Effects: The Sun; 4) The Earth's Environment; 5) Trapped Radiation Belts; 6) Aurora Are Everywhere; 7) Spacecraft Interactions; 8) Atmospheric Effects; 9) Contaminant Effects on Materials; 10) Meteoroid/Debris Effects on Materials; 11) Spacecraft Surface Charging; 12) Surface Discharge Effects; 13) Internal Electrostatic Discharge--Satellite Killer; 14) Plasma Interactions DS-1 Ion Engines; 15) Radiation Effects on Spacecraft Systems and Materials; 16) Total Ionizing Dose Effects Total Ionizing Dose Effects; 17) Man-Made Sources of Space Effects Man-Made Sources of Space Effects; and 18) Space Environments Versus Interactions.