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Trace elements in biological systems: nuclear techniques app.

Nuclear techniques are very useful in the simultaneous determination of many trace elements in biological samples; the sensitivity depends on the method and on the elements in study and in many cases is better than 0;1 ppm. Proton-induced X-ray fluorescence and alpha-particle elastic diffusion techniques are described; the methods of sample preparation, the sensitivity obtained and some experimental results are included.

Alpha Particles↗

Optical excitation of LiF:Mg,Ti following alpha and beta irradiation.

It is demonstrated experimentally that optical excitation of irradiated LiF:Mg,Ti (TLD-100) by 4 eV photons has the same effect for both alpha particle (high-ionisation density) irradiation and photon/electron irradiation. In both cases, peak 5a converts to peak 4 causing peak 4 to increase following the bleach. Such an observation is consistent with the major premise of track structure theory that radiation effects following heavy changed particle (HCP)/neutron irradiation are due exclusively to the interaction of the secondary electrons created by the HCP slowing down.

Alpha Particles↗

Radioimmunotherapy for acute leukemia.

BACKGROUND: The use of monoclonal antibodies to deliver radioactive isotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native monoclonal antibodies. In this article, we summarize the role of radioimmunotherapy in the treatment of leukemia. METHODS: The authors reviewed the published clinical trials of radioimmunotherapy in acute leukemia. RESULTS: Radioimmunoconjugates that emit beta-particles, such as 131I-anti-CD33, 90Y-anti-CD33, 131I-anti-CD45, and 188Re-anti-CD66c, deliver significant doses of radiation to the bone marrow and may be particularly effective when used as part of a conditioning regimen for hematopoietic stem cell transplantation. Radioimmunoconjugates that emit short-ranged alpha-particles, such as 213Bi-anti-CD33, are better suited for the treatment of low-volume or residual disease. CONCLUSIONS: Radiolabeled antibodies can be administered safely to patients with advanced leukemias and have significant antileukemic activity. Radiolabeled antibodies can potentially intensify the antileukemic effects of conditioning regimens when used in conjunction with hematopoietic stem cell transplantation. Whether or not radiolabeled antibodies improve the outcome of patients with leukemia remains to be demonstrated by randomized studies.

Acute Disease↗

Radiotoxicity of the alpha-emitting bone-seeker 223Ra injected intravenously into mice: histology, clinical chemistry and hematology.

BACKGROUND: The alpha-emitter 223Ra, which localizes in osteoblastic active zones, including on skeletal surfaces and in osteoblastic metastases, has recently been introduced as a potential therapeutic agent against skeletal metastases. Here, the adverse effects of high dosages in animals were investigated. MATERIALS AND METHODS: Balb/c mice received intravenously (i.v.) either 1250, 2500, or 3750 kBq/kg of dissolved 223RaCl2 and were followed in the initial toxicity phase. At the 4-week end-point, the animals were sacrificed and blood samples were collected to study the effects on clinical chemistry and hematological parameters. Selected organs were weighed and tissue samples examined by microscopy. RESULTS: Treatment with 223Ra caused a dose-related minimal to moderate depletion of osteocytes and osteoblasts in the bones. Furthermore, a dose-related minimal to marked depletion of the hematopoietic cells in the bone marrow, and a minimal to slight extramedullary hematopoiesis in the spleen and in the mandibular and mesenteric lymph nodes were observed. The LD50 for acute toxicity, defined as death within 4 weeks of receiving the substance, was not reached. CONCLUSION: This study demonstrated that high doses of the bone-seeker 223Ra did not completely inactivate the blood-producing cells. The relatively high tolerance to skeletal alpha doses was probably caused by the surviving pockets of red bone marrow cells beyond the range of alpha particles from the bone surfaces, and the recruitment of peripheral stems cells.

Alpha Particles↗

Discovery of new etchants for CR-39 detector.

After reporting the excellent etching properties of molten Ba(OH)2 8H2O as an etchant, we now report some more new and efficient etchants for CR-39 detector. CR-39 detectors were irradiated with fission fragments and alpha particles with a thin 252Cf source. The irradiated detectors were etched in a number of our newly introduced etching solutions as well as in conventionally used 6 M NaOH at 70 degrees C. The newly prepared etching solutions included NaOH/ethanol and NaOH/1-propanol. Processing conditions were optimized for these etchants. From fission and alpha track diameters, bulk etching velocity (VB), track etching velocity (VT), etching efficiency (eta) and their activation energies were determined and compared with that obtained for 6M NaOH at 70 degrees C.

1-Propanol↗

Structural studies on the microfibrillar proteins of wool: characterization of the alpha-helix-rich particle produced by chymotryptic digestion.

The alpha-helix-rich particle produced by chymotryptic digestion of the reduced and alkylated microfibrillar proteins of wool was characterized by physicochemical methods. The preparations were homogeneous with respect to size and the particle molecular weight was found to be 50 200 +/- 2 000. Hydrodynamic methods indicated a length of about 20 nm for the particle. The properties of the particle, derived from two methods of isolation of the microfibrillar proteins, were identical and were also independent of the type of wool used. From a consideration of the molecular weight in denaturing solvents and from cross-linking experiments with dimethyl suberimidate a four-chain structure, consisting of a pair of double-stranded alpha-helices, is proposed for the particle.

Animals↗

Radiation response of primary human skin fibroblasts and their bystander cells after exposure to counted particles at low and high LET.

PURPOSE: To investigate the dependence of bystander effects on linear energy transfer (LET) in the low dose region. MATERIALS AND METHODS: The single-ion microbeam of the Physikalisch-Technische Bundesanstalt (PTB) was used to irradiate confluent primary human skin fibroblasts. Cells plated on a special irradiation dish were targeted with 10 MeV protons (LET 4.7 keV/microm) and 4.5 MeV a-particles (LET 100 keV/microm). During exposure, the cells were confluent allowing signal transfers through both gap junctions and diffusion. RESULTS: For 10 MeV protons the clonogenic capability was significantly higher after exposure to 70 protons (0.31 Gy) compared with unirradiated cells. For higher doses the survival curve was exponential. Exposure of only 10% of all nuclei resulted in a similar radiation response in the low dose region. For higher doses up to 2.2 Gy no cell killing was observed. For 4.5 MeV alpha-particles an exponential survival curve was obtained. Irradiation of only 10% of all cell nuclei resulted in an survival curve as had been expected in the absence of any bystander effect. CONCLUSION: The type and extent of bystander effects turned out to be dependent on the particles' LET and are likely to depend also on the cell line used and the techniques applied.

Alpha Particles↗

Validation of 213Bi-alpha radioimmunotherapy for multiple myeloma.

The efficacy of radioimmunotherapy (RIT) with beta emitters has been clinically demonstrated in the treatment of refractory forms of lymphoma. Alpha-emitting radionuclides with a short half-life are also good potential candidates for RIT directed at tumor targets easily accessible to radioimmunoconjugate molecules and small enough to benefit from the short range of alpha particles (<100 microm). The purpose of this study was to demonstrate the feasibility of ex vivo purging of multiple myeloma-invaded bone marrow. Tumor cells were targeted by a specific monoclonal antibody (B-B4) coupled to 213Bi by a chelating agent (pentaacetic triamine diethylene p-aminobenzyl acid). The efficacy of alpha-RIT was assessed in vitro by analysis of thymidine incorporation, cell mortality, apoptosis of myeloma cells, and the study of nonspecific irradiation of hematopoietic cell lines not recognized by B-B4-pentaacetic triamine diethylene p-aminobenzyl acid immunoconjugate. High dose-dependent cell mortality of myeloma cells was found with radiolabeled B-B4, and this mortality was total at 30 kBq/10(5) cells. Cells were found in apoptotic state at rates of up to 40% for a dose of 7.4 kBq/10(5) cells. Nonspecific mortality was low compared with specific mortality (up to 1%).

Alpha Particles↗

Subpopulations of high density lipoproteins in homozygous and heterozygous Tangier disease.

Tangier disease (TD) is characterized by severe high-density lipoproteins (HDL) deficiency, hypercatabolism of HDL constituents, impaired cellular cholesterol efflux, and mutations in the gene of ATP-binding cassette 1 (ABC-1). In the present study, we determined plasma lipid and apolipoprotein levels, and HDL subpopulations, in 110 subjects from a large TD kindred in which the proband was homozygous for an A-->C missense mutation at nucleotide 5338 of the ABC-1 transcript. In the proband HDL-C, apoA-I, and apoA-II concentrations were 2, 1, and 2 mg/dl, respectively, apoA-I was present only in prebeta(1), while apoA-II was found free of apoA-I in two distinct alpha mobility subpopulations with different sizes. The smaller size particles contained only apoA-II while the larger one contained apoA-II and apo(a). Relative to unaffected male relatives (n=30), male heterozygotes (n=21) had significant reductions (P<0.001) in plasma HDL-C (-45%), apoA-I (-34%), apoA-II (-59%), apoA-IV (-40%), Lp(a) (-62%), and apoB (-55%) concentrations, and a significant increase (P<0.05, +33%) in plasma apoC-III levels. Female heterozygotes (n=11) similarly had significant reductions (P<0.001) in the concentrations of plasma HDL-C (-42%), apoA-I (-27%), apoA-II (-52%), Lp(a) (-27%), and (P<0.01) apoA-IV (-28%), apoB (-13%), and a significant increase (P<0.05) in plasma apoE levels (+29%) as compared to unaffected female relatives (n=41). Large size HDL subpopulations, especially the two LpA-I particles: alpha(1) and prealpha(1) were dramatically reduced in both male and female heterozygotes relative to their unaffected family members. Since apoA-II decreased more than apoA-I in both male and female heterozygotes, the ratios of apoA-I/apoA-II were significantly (P<0.01) increased. The prevalence of CHD was 60% higher in the 32 heterozygotes than in the 71 unaffected relatives even though the latter group was on average 7 years older. We conclude that TD homozygotes have only prebeta(1) apoA-I-containing HDL subpopulations, while heterozygotes have HDL that is selectively depleted in the large alpha(1), prealpha(1), and alpha(2), prealpha(2) subpopulations, resulting in HDL particles that are small in size, poor in cholesterol, but relatively enriched in apoA-I compared to those of their unaffected relatives. These abnormalities appear to result in a higher risk of CHD in heterozygotes than in unaffected controls.

Adult↗

Genomic instability and tumorigenic induction in immortalized human bronchial epithelial cells by heavy ions.

Carcinogenesis is postulated to be a progressive multistage process characterized by an increase in genomic instability and clonal selection with each mutational event endowing a selective growth advantage. Genomic instability as manifested by the amplification of specific gene fragments is common among tumor and transformed cells. In the present study, immortalized human bronchial (BEP2D) cells were irradiated with graded doses of either 1GeV/nucleon 56Fe ions or 150 keV/micrometer alpha particles. Transformed cells developed through a series of successive steps before becoming tumorigenic in nude mice. Tumorigenic cells showed neither ras mutations nor deletion in the p16 tumor suppressor gene. In contrast, they harbored mutations in the p53 gene and over-expressed cyclin D1. Genomic instability among transformed cells at various stage of the carcinogenic process was examined based on frequencies of PALA resistance. Incidence of genomic instability was highest among established tumor cell lines relative to transformed, non-tumorigenic and control cell lines. Treatment of BEP2D cells with a 4 mM dose of the aminothiol WR-1065 significantly reduced their neoplastic transforming response to 56Fe particles. This model provides an opportunity to study the cellular and molecular mechanisms involved in malignant transformation of human epithelial cells by heavy ions.

Alpha Particles↗

Experimental calculations of droplet diffusion in a low-pressure cloud chamber.

A low-pressure cloud chamber was used for several years to display the tracks created by the passage of ionizing particles through vapors of interest. The spatial distributions of the ions that were formed were of special interest, but the accuracy with which these distributions could be determined was reduced by the presence of diffusion. This meant that the droplets, when photographed, had moved significantly away from the point of creation of the parent ion. In the present investigation photographs obtained by previous workers have been analyzed in an attempt to quantify the extent to which the droplets had diffused. The results suggest that the diffusion, when converted to standard density (1000 kg/m3), was independent of the pressure inside the cloud chamber and the mixture used. It could be represented by a one-dimensional root-mean-square diffusion distance whose value was calculated to be 2.42 +/- 0.04 nm. Values for the diffusion of thermalized electrons (< approximately 4 eV) before capture to form negative ions were also calculated. They appeared to lie in the range 3.5-5.0 nm, and were again independent of the pressure and nature of the mixture. The magnitude of the diffusion was large enough to mask any measurable prediffusion structure for a distance in the region of 10 nm radially around the track path of the alpha-particle and proton tracks analyzed.

Alpha Particles↗

Radiation risk estimation based on activity measurements of zirconium oxide implants.

Implants made form zirconium dioxide exhibit higher specific radionuclide activities of the uranium-radium and thorium series than metallic and aluminum implants. This study presents data on activity measurements performed on different samples of ZrO2 raw material (powder) and on the ceramic joint heads belonging to it to formulate a correlation between the specific radionuclide activities of the uranium-radium and thorium series in the raw material, the flux density of the alpha particle leaving the implant surface, and the annual dose of the tissue surrounding the implant. Based on this experimental study, an equation for defining the limits of the specific activities in raw material is proposed, taking into account the long-lived radionuclides (key nuclides) of the uranium-radium and thorium series weighted with their relative dose contributions from alpha emitters.

Alpha Particles↗

Low doses of alpha- and gamma-radiation enhance DNA thermal stability.

Isolated calf thymus DNA in buffered solutions has been exposed to 0-150 Gy of alpha- and gamma-radiation. The effects of alpha- and gamma-radiation on the thermal stability and electrophoretic mobility of the DNA molecules have been studied by UV spectroscopic 'melting' and Pulsed Field Gel Electrophoresis (PFGE), respectively. The observed thermal denaturation parameters were fitted to the energy propagation descriptive model. The experimental results for the samples exposed to relatively low (low) doses indicate an increased thermal stability and a reduced mobility over that of the controls. The expected overall degradation of the DNA molecules was confirmed for the samples exposed to high doses. Our results are in good agreement with the predictions of the energy propagation model, which now is also tested in the low dose region and for an additional type of ionising radiation (alpha-particles). Our findings are consistent with conformational changes at low doses resulting in a DNA form characterised by localised alterations, which affect the energy flow along the DNA molecule.

Alpha Particles↗

Comparative dosimetry of BEIR VI revisited.

The BEIR VI Committee applied recent developments in the comparative dosimetry of radon exposures in mines and homes to evaluate the so-called K-factor used to extrapolate the excess relative risk of lung cancer determined for underground uranium miners to exposures in homes. This paper describes methodological aspects of these developments that were specified ambiguously in the BEIR VI report. Specifically, in the section dealing with dosimetry (Appendix B of the BEIR VI report), the K-factor was unusually defined in terms of exposure to radon gas (K(gas)), and not in terms of exposure to potential alpha energy (K). An incorrect value of unity was calculated for K(gas). This implies a value of 0.44 for K. In this paper, we describe how application of the ICRP Publication 66 lung and dosimetric models to evaluate the regional lung dose per unit exposure to potential alpha-energy in mines and homes yields the value of K = unity. This confirms the BEIR VI Committee's choice of K = 1 for application in their risk extrapolation model. The paper also reviews the use of doses to specific sub-cellular targets in the evaluation of K. This yields a somewhat greater divergence in the corresponding estimates of K, but again an overall average value of K = unity. The paper describes the methods used to calculate alpha particle hit probabilities for specific subcellular targets, and the resulting estimates of single- and multiple-hit probabilities obtained for exposures in mines and homes, as a function of the respective exposure rates.

Alpha Particles↗

[Evaluation of genetic consequences of 238Pu incorporation into mammals].

The genetic effects of gonadal burdens of 238Pu after single injection were studied in male mice. The activity of plutonium was 7 to 1850 Bk/g. The average doses of accumulated alpha-particles in testis varied from 2 to 96 Gy.10(-2), the dose rate being 0.004 to 1 Gy.10(-2) per day. The genetic end points are: the dominant lethal mutation rate; the frequency of reciprocal translocations; the recessive lethal mutation rate and frequency of abnormal sperm head morphology. For all tests used, no linear dependence of the effect on the alpha-dose was observed. The RBE value of alpha-irradiation was 10-20 relative to chronic gamma-irradiation.

Alpha Particles↗

Modelling radiation loads to detectors in a SNAP mission.

In order to investigate the degradation of optical detectors of the Supernova Acceleration Project (SNAP) space mission because of irradiation, a three-dimensional model of the satellite has been developed. A realistic radiation environment at the satellite orbit, including both galactic cosmic rays and cosmic ray trapped in radiation belts, has been taken into account. The modelling has been performed with the MARS14 Monte Carlo code. In a current design, the main contribution to dose accumulated in the photo-detectors is shown to be due to trapped protons. The contribution of primary alpha particles is estimated. Predicted performance degradation for the photodetector for a four-year space mission is 40% and this can be reduced further by means of shielding optimisation.

Alpha Particles↗

Visual phenomena noted by human subjects on exposure to neutrons of energies less than 25 million electron volts.

Six subjects reported multiple starlike flashes and short streaks on exposure to neutrons of energies up to 25 million electron volts. The probable mechanism is interaction with the retinal rods by proton recoils and by alpha particles released from neutron reactions with carbon and oxygen. These observations are similar to light flashes and streaks seen by astronauts who are exposed to high-energy cosmic rays on translunar flight.

Alpha Particles↗

Observations on the background spectra of four LaCl 3 Ce scintillation detectors.

Our laboratory has purchased four LaCl (3)(Ce) scintillation crystals over the course of the last year for evaluation as part of an environmental management research and development project. In addition to the expected content of naturally radioactive (138)La, we have found that all four of these detectors are contaminated to various degrees with alpha particle emitting nuclides that we have determined to be (227)Ac and its daughters. The impact of these radionuclides on the background spectra and, thus, on the detection sensitivity of these detectors is presented and discussed.

Alpha Particles↗