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Alpha and fission fragment autoradiography with superimposed tissue images in CR-39 plastic.

A technique is described by which the distributions of both fissionable and alpha-emitting radionuclides in histological sections of lung are visualised in the nuclear track recording plastic CR-39. Fission fragments and alpha-particles from radionuclides contained within the section register as tracks in CR-39 and an image of the tissue structure is induced, superimposed upon the track distribution, by means of low-energy (less than 1 MeV) alpha-particles from an external 238Pu source. Thus accurate apposition of the track distribution and tissue structure is achieved. The efficiencies of this system for alpha-particle and fission fragment detection are 0.51 +/- 0.09 (SD) and 0.48 +/- 0.08 (SD) respectively.

Alpha Particles↗

An electrostatic precipitator for the study of airborne radioactivity.

An system has been developed to measure airborne radioactivity using electrostatic precipitation for collection and alpha-particle spectroscopy for detection. Features include good energy resolution (e.g. 170 and 300 KeV for full-width half maximum and full-width tenth maximum for 7.7-MeV alpha particles using a 7-cm2 area detector; and 52- and 122-KeV, respectively, using 1.2-cm2 area detector) and versatile computer control for collection, counting and data reduction. Aerosols bearing the radioactive atoms are deposited on a foil tape by electrostatic precipitation for a predetermined time after which the foil is moved under a solid-state detector to count the alpha-particle emissions. Activities are determined at the same frequency as samples are collected. Helium gas can be introduced at the detector to reduce energy loss and improve resolution. Although in principle certain aerosol sizes could be difficult to collect, in practice no difficulties were observed for typical environmental conditions, provided sufficiently low air-sampling rates were used. One important application is the measurement of 222Rn daughters. The sensitivity is such that detection of individual daughter concentrations less than 0.1 pCi/l. with only a 10% counting error is possible.

Air Pollution, Radioactive↗

Alpha hit frequency due to radon decay products in human lung cells.

PURPOSE: To calculate the hit probabilities by alpha-particles emitted by radon progeny for basal and secretory cell nuclei in the epithelium of the human tracheobronchial tree. MATERIALS AND METHODS: The equilibrium activities on the surface of airway tubes were calculated using the ICRP66 model. The stopping-power and ranges of alpha-particles in tissue were adopted from ICRU49. A semi-analytical method for determining the alpha-particle fluence rate in tissue was applied. The distributions of secretory and basal cells throughout the tracheobronchial tree were as given by Mercer et al. (1991). RESULTS: The probability to hit basal cell nuclei is three-to-four times smaller than for secretory cell nuclei in the bronchial region (BB). However, the total number of traversed basal cell nuclei is greater because of the larger volume abundance of basal cells in BB. The total number of secretory cell nuclei hit in the bronchiolar region (bb) is larger than that in BB because the volume abundance of secretory cells in bb is larger than that in BB. CONCLUSIONS: Basal cells are more sensitive to alpha-radiation than secretory cells. This finding is based on the analysis of the relative number of cell hits and the relative frequencies of lung cancer induction in BB and bb.

Aerosols↗

Detection of buried explosives using portable neutron sources with nanosecond timing.

Significant reduction of time needed to identify hidden explosives and other hazardous materials by the "neutron in, gamma out" method has been achieved by introducing timed (nanosecond) neutron sources-the so-called nanosecond neutron analysis technique. Prototype mobile device for explosives' detection based on a timed (nanosecond) isotopic (252)Cf neutron source has been created. The prototype is capable of identifying 400 g of hidden explosives in 10 min. Tests have been also made with a prototype device using timed (nanosecond) neutron source based on a portable D-T neutron generator with built-in segmented detector of accompanying alpha-particles. The presently achieved intensity of the neutron generator is 5x10(7)n/s into 4pi, with over 10(6) of these neutrons being correlated with alpha-particles detected by the built-in alpha-particle detector. Results of measurements with an anti-personnel landmine imitator are presented.

Blast Injuries↗

Comparative study of G2 delay and survival after 241 Americium-alpha and 60cobalt-gamma irradiation.

Survival and G2 dalay following exposure to either 60Cobalt-gamma-rays or 241Americium-alpha-particles were studied in eight mammalian cell lines of human and animal origin including human fibroblasts from normal individuals and from patients with Ataxia telangiectasia or Fanconi's anemia. For both endpoints the effectiveness of alpha particles was greater as compared to gamma-rays. RBE values for G2 delay (4.6-9.2) were in general comparable to RBE values derived from initial slopes of survival curves (RBE alpha) but higher compared to the ratio of mean inactivation doses (RB-DML). Ataxia cells were particularly sensitive to cell killing by gamma-irradiation (D37 = 0.57 Gy), however, showed average sensitivity to alpha-particles of high LET (D37 = 0.30 Gy). With the exception of Ataxia cells, cell killing and G2 delay seem to be related processes if individual cell cycle parameters are taken into account.

Alpha Particles↗

Radionuclide-antibody conjugates for single-cell cytotoxicity.

BACKGROUND: Radioimmunotherapy has primarily utilized high-energy beta-particles, which are intended to kill macroscopic tumor masses. Such conjugates do not kill single cells or micrometastases efficiently. For killing single cells, it may be preferable to use radiation with a much shorter path length, such as alpha-particles or Auger or conversion electrons. METHODS: This selective review focuses on the use of radiolabeled antibody (Ab) conjugates to achieve single-cell kill. The advantages and disadvantages of particular types of radionuclides, the significance of intracellular localization of the Ab, and the potential clinical application of this approach are discussed. Potentially useful radionuclides are listed. RESULTS: Auger and conversion electrons can kill cells effectively, with at least 6 logs of cell kill. Abs on the cell surface are only slightly less potent than Abs internalized into the cytoplasm, and this is consistent with theoretical considerations. alpha-Particles kill single cells very effectively, but the short half-lives of the available alpha-particle emitters are probably a disadvantage. High-energy beta-particles can also kill single cells if they bind in sufficient amounts, but their disadvantage appears to be greater nonspecific toxicity. CONCLUSIONS: Single-cell kill can be obtained with radionuclide-Ab conjugates. The selection of the optimal radionuclide may depend on the details of the clinical situation, such as the size and accessibility of the tumor burden, and the particular Ab to be used. Direct comparisons of various radionuclides are required in order to identify the optimal approach. However, for single-cell kill, as required for therapy of micrometastases, the use of Auger and conversion electron emitters appears to have substantial advantages. While current methods limit the applicability of this approach to Abs having a high level of binding, it may be applicable to lower-density antigens if higher specific activities or more potent radionuclides can be used. Tumor cure may require a mixture of radionuclides intended to kill both single cells and large tumor masses.

Alpha Particles↗

Heavy charged particles produce a bystander effect via cell-cell junctions.

Radiation-induced damage to living cells results from either a direct hit to cellular DNA, or from indirect action which leads to DNA damage from radiation produced radicals. However, in recent years there is evidence that biological effects such as cell killing, mutation induction, chromosomal damage and modification of gene expression can occur in a cell population exposed to low doses of alpha particles. In fact these doses are so low that not all cells in the population will be hit directly by the radiation. Using a precision alpha-particle microbeam, it has been recently demonstrated that irradiated target cells can induce a bystander mutagenic response in neighboring "bystander" cells which were not directly hit by alpha particles. Furthermore, these results suggest that gap-junction mediated cell-to-cell communication plays a critical role in this bystander phenomenon. The purpose of this section is to describe recent studies on bystander biological effects. The recent work described here utilized heavy charged particles for irradiation, and investigated the role of gap-junction mediated cell-cell communication in this phenomenon.

Alpha Particles↗

Increased bystander mutagenic effect in DNA double-strand break repair-deficient mammalian cells.

PURPOSE: We have shown previously that when monolayer cultures of Chinese hamster ovary (CHO) cells are exposed to very low fluences of alpha-particles, HPRT mutations are induced in non-irradiated 'bystander' cells in the population. The present investigation was designed to examine the role of DNA repair in this process. MATERIALS AND METHODS: The DNA double-strand repair-deficient mutant cell line xrs-5 was exposed to mean doses of alpha-particles as low as 0.04 cGy whereby less than 1% of the nuclei were traversed by an alpha track and thus received any radiation exposure. RESULTS: With this very low alpha-particle fluence, most of the cells in the xrs-5 population appeared to be at risk for the induction of mutations, indicating a much larger bystander effect than observed with wild-type CHO cells. Molecular structural analyses showed that xrs-5 mutants primarily involved partial and total gene deletions as opposed to wild-type cells where point mutations predominated in bystander cells. CONCLUSIONS: These results indicate a very large bystander effect in xrs-5 cells. They support the hypothesis that unrepaired or misrepaired double-strand breaks (DSB), arising from opposed DNA lesions, enhance the sensitivity of bystander cells in xrs-5 cultures to the induction of mutations.

Alpha Particles↗

Half-life values for DNA double-strand break rejoining in yeast can vary by more than an order of magnitude depending on the irradiation conditions.

Yeast cells in stationary phase were exposed under oxic or anoxic conditions to sparsely (30 MeV electrons) or densely (3.5 MeV alpha-particles) ionizing radiation. For all four experimental set-ups postirradiation treatment of cells was the same, i.e. cells were kept under oxic conditions in non-growth medium at 30 degrees C. Double-strand break (dsb) rejoining was measured during this treatment yielding the following results: (1) half-life values ranged from < 60 min (electrons, anoxia) to 3.8 h (low doses of electrons, oxia), 7 h (alpha-particles, anoxia), 10 h (high doses of electrons, oxia) and 13 h (alpha-particles, oxia). (2) In the case of exposure of oxic cells to electrons a biphasic rejoining kinetics is observed with a dose-dependent increase of the fraction of the slow component. These results suggest that half-life values of dsb rejoining in a given cell depend on physical, chemical and biological parameters. The rejoining of dsb slows down with increasing LET, being probably due to the increasing complexity of dsb. Oxygenation of cells at the time of irradiation affects half-life values, indicating that radiation chemistry plays an important role. The biphasic rejoining kinetics observed for dsb induced by electrons in oxic cells is interpreted in terms of a dose-dependent change of chromatin structure hindering the interaction between damaged chromatin and the rejoining enzymes rather than by two chemically distinct types of dsb with differing half-life values.

Alpha Particles↗

The in vitro radiobiology of astatine-211 decay.

Chinese hamster V79 cells in culture were exposed to astatine-211, an alpha-particle-emitting radiohalogen. The dose-log survival response was linear with no detectable shoulder. Cells in monolayers had a D0 of 1.0 microCi/ml. Suspended cells had a D0 of 0.60 microCi/ml with a cellular uptake of 2.5 fCi/cell; this is equal to approximately 1.5 alpha-particle traversals per cell nucleus. The frequencies of chromosome and chromatid breaks were linear with dose, but the number declined rapidly with time. These data are discussed in relation to published alpha-particle beam studies and the potential use of 211At in radionuclide therapy.

Alpha Particles↗

Radiation-induced chromosomal instability in human fibroblasts: temporal effects and the influence of radiation quality.

PURPOSE: To determine whether chromosomal instability is induced in human diploid fibroblasts by ionizing radiation and to investigate the effects of radiation quality by comparing X-rays, neutrons and alpha-particles. MATERIALS AND METHODS: Cells from two human diploid fibroblast lines, HF12 and HF19, were irradiated and analysed cytogenetically at 3, 20 and 35 population doublings post-irradiation. RESULTS: Exposure of HF19 cells to neutrons and alpha-particles resulted in a consistently increased frequency of unstable aberrations, particularly chromatid-type aberrations, compared to control cultures. Aberration frequency after X-irradiation was not significantly greater than controls at 20 population doublings but was significantly increased after 35 population doublings, although not to the same level as that following neutron or alpha-irradiation. No chromosomal instability was demonstrated in the progeny of HF12 cells after X-, neutron or alpha-particle irradiation. CONCLUSIONS: The data are consistent with the progeny of irradiated HF19 cells expressing chromosomal instability. All three radiations are effective in inducing instability, but the expression of the phenotype is influenced by radiation quality. The absence of radiation-induced chromosomal instability in HF12 cells may reflect the influence of genetic factors.

Alpha Particles↗

Adaptive response and the bystander effect induced by radiation in C3H 10T(1/2) cells in culture.

This paper discusses two phenomena of importance at low doses that have an impact on the shape of the dose-response relationship. First, there is the bystander effect, the term used to describe the biological effects observed in cells that are not themselves traversed by a charged particle, but are neighbors of cells that are; this exaggerates the effect of small doses of radiation. Second, there is the adaptive response, whereby exposure to a low level of DNA stress renders cells resistant to a subsequent exposure; this reduces the effect of low doses of radiation. The present work was undertaken to assess the relative importance of the adaptive response and the bystander effect induced by radiation in C3H 10T(1/2) cells in culture. When the single-cell microbeam delivered from 1 to 12 alpha particles through the nuclei of 10% of C3H 10T(1/2) cells, more cells were inactivated than were actually traversed by alpha particles. The magnitude of this bystander effect increased with the number of particles per cell. An adaptive dose of 2 cGy of gamma rays, delivered 6 h beforehand, canceled out about half of the bystander effect produced by the alpha particles.

Adaptation, Physiological↗

Experimental equivalent cluster-size distributions in nanometric volumes of liquid water.

Ionisation cluster-size distributions in nanometric volumes of liquid water were determined for alpha particles at 4.6 and 5.4 MeV by measuring cluster-size frequencies in small gaseous volumes of nitrogen or propane at low gas pressure as well as by applying a suitable scaling procedure. This scaling procedure was based on the mean free ionisation lengths of alpha particles in water and in the gases measured. For validation, the measurements of cluster sizes in gaseous volumes and the cluster-size formation in volumes of liquid water of equivalent size were simulated by Monte Carlo methods. The experimental water-equivalent cluster-size distributions in nitrogen and propane are compared with those in liquid water and show that cluster-size formation by alpha particles in nitrogen or propane can directly be related to those in liquid water.

Algorithms↗

Genomic instability in human lymphocytes irradiated with individual charged particles: involvement of tumor necrosis factor alpha in irradiated cells but not bystander cells.

Exposure to ionizing radiation can increase the risk of cancer, which is often characterized by genomic instability. In environmental exposures to high-LET radiation (e.g. 222Ra), it is unlikely that many cells will be traversed or that any cell will be traversed by more than one alpha particle, resulting in an in vivo bystander situation, potentially involving inflammation. Here primary human lymphocytes were irradiated with precise numbers of 3He2+ ions delivered to defined cell population fractions, to as low as a single cell being traversed, resembling in vivo conditions. Also, we assessed the contribution to genomic instability of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFA). Genomic instability was significantly elevated in irradiated groups (> or = two-fold over controls) and was comparable whether cells were traversed by one or two 3He2+ ions. Interestingly, substantial heterogeneity in genomic instability between experiments was observed when only one cell was traversed. Genomic instability was significantly reduced (60%) in cultures in which all cells were irradiated in the presence of TNFA antibody, but not when fractions were irradiated under the same conditions, suggesting that TNFA may have a role in the initiation of genomic instability in irradiated cells but not bystander cells. These results have implications for low-dose exposure risks and cancer.

Bystander Effect↗

Genetic and cytogenetic markers of exposure to high-linear energy transfer radiation.

It has been suggested that the more closely spaced, clustered DNA breaks seen with high-LET radiations are more likely to result in chromosome intrachanges than in chromosome interchanges. We determined whether analysis of the spectra of chromosome aberrations or Hprt gene mutations in CHO-K1 cells could detect a shift to more chromosome intrachanges and therefore distinguish exposure to high-LET radiation from exposure to low-LET radiation, and whether alterations in the processing of DNA breaks would influence this process. Both the frequency and type of chromosome aberrations and Hprt gene mutations were determined in CHO-K1 and xrs-5 cells exposed to 60Co gamma rays or 212Bi alpha particles. Xrs-5 cells are a radiosensitive derivative of CHO-K1 cells that are defective in rejoining of DNA double-strand breaks. The ratio of dicentrics to centric rings (F ratio) was significantly lower in CHO-K1 and xrs-5 cells exposed to alpha particles, consistent with a shift to more chromosome intrachanges with higher LET. In contrast, the frequency of large interstitial deletions at the Hprt locus, determined by multiplex polymerase chain reaction-based exon deletion analysis, was the same for both gamma-ray- and alpha-particle-exposed cells in each of the cell lines. Thus the F ratio can distinguish high-LET from low-LET radiations, and the end point is not influenced by differences in the processing of DNA double-strand breaks. The analysis of the spectrum of Hprt mutations, however, appears unable to discriminate low LET from high LET.

Alpha Particles↗

Microdosimetry of alpha-irradiated lung.

Measurements have been made on the fractions of tissue affected and distributions of energy deposited when rat and human lung are irradiated by alpha particles. Thin sections of alveolar tissue were examined in an image analyser and an imaginary 239PuO2 particle was placed in an alveolar sac. The hypothetical alpha particles were followed to the ends of their tracks so the effects of the material's real structure could be examined in detail. It is shown that a fair comparison exists with results previously obtained with hamster lung. In addition, the measurements actually made with human lung correlate well with predictions based on the rat lung measurements. Finally, it is confirmed that the approximation of a uniform, structureless lung is a poor one.

Alpha Particles↗

Dosimetric assessment of radon in a vegetable system.

An alpha-dose calculation due to radon uptake in anthers of Tradescantia, clone 4430, has been performed. Probability distribution density of the dose in the pollen mother cells was calculated by means of a model that simulates the interaction of separate alpha-particles with these cells. It is shown that alpha-radiation from either radon or its decay products surrounding the buds does not reach pollen mother cells because of the short-range alpha-particles. However, it is suggested that radon diffuses through the gap structure of the bud to the anther from which a radon-gas adsorption process takes place. Absorbed-dose calculations in the anther are discussed as well as their relationship to the experimental results of micronucleus induction in pollen mother cells. The radon concentration interval used (0.85 kBq m(-3)-98.16 kBq m(-3)) is equivalent to the exposure to an average environmental radon concentration (40 Bq m(-3)) for 2.3 months or 22.1 years, respectively. The lowest radon concentration to induce micronuclei was 12.1 kBq m(-3), which is 15 times in excess of that adopted for old buildings in Canada.

Air Pollution, Indoor↗

Radiological sampling and analytical methods for National Primary Drinking Water Regulations.

Radiological sampling and analysis performed under the National Interim Primary Drinking Water Regulations were evaluated for the U.S. Environmental Protection Agency (EPA) Office of Drinking Water to consider whether any changes should be recommended. The authors reviewed the analytical screening scheme; sample collection, storage and analysis procedures; selection of analytical methods; reliability of results; and possible future needs. The main problem in the program has been dependence on a screening scheme of gross alpha-particle activity measurement and 226Ra analysis for predicting elevated 228Ra levels to determine compliance with the maximum contaminant level (MCL) for Ra. In some aquifers, 228Ra levels have been found to be unrelated to 226Ra levels. Several alternatives are discussed to eliminate this problem. A secondary problem is that the measurement for assuring compliance with the MCL for gross alpha-particle activity minus Ra, Rn and U uses chemical U analysis and assumes equilibrium of 238U and 234U. Because some ground waters are known to be at disequilibrium, radiometric U analysis is needed for those gross alpha-particle activities and chemical U values that could result in an erroneous conclusion relative to the MCL. In addition, studies were recommended for determining analytical uncertainties and assuring reliable sampling and sample maintenance; improvements in the system for accepting methods were suggested; and methods were identified for several radionuclides not currently in the analytical program that may be needed to assure absence of elevated radiation doses and could be useful for identifying trace contaminants.

Alpha Particles↗