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At least 19 recordsLinked to original sources
PubMed1996

The biological effectiveness of radon-progeny alpha particles. V. Comparison of oncogenic transformation by accelerator-produced monoenergetic alpha particles and by polyenergetic alpha particles from radon progeny.

Generation of estimates of risk caused by exposure to radon in the home, either from miner data or from A-bomb data, requires several scaling factors such as for dose, dose rate and radiation quality, and possible synergisms. Such scaling factors are best developed from laboratory-based studies. Two possible sources of alpha particles for such studies are (1) a polyenergetic spectrum, generated directly by radon and its progeny, or (2) a series of monoenergetic alpha particles. We compare here the results of oncogenic transformation from studies using both systems. At the Columbia University Radiological Research Accelerator Facility (RARAF), C3H 10T1/2 cells were irradiated with alpha particles of various energies, with defined LETs from 70 to 200 keV/mum. At Pacific Northwest Laboratory, cells from the same stock were exposed to alpha particles from radon gas and its progeny, which were in equilibrium with the culture medium. There was good agreement between the results of oncogenic transformation experiments using the two different exposure systems. Apart from the experimental transformation frequencies themselves, such a comparison requires (1) reliable dosimetry at both facilities and (2) estimated LET distributions for the polyenergetic alpha-particle irradiator. Thus this good agreement gives some confirmation to the technique which is used to fold together oncogenic transformation rates from monoenergetic alpha particles to yield a predicted rate for a spectrum of alpha particles.

Alpha Particles↗
PubMed1993

Radiobiology of alpha particles. IV. Cell inactivation by alpha particles of energies 0.4-3.5 MeV.

In this report the effectiveness of low-energy alpha particles in the range 0.4 to 3.5 MeV for cell killing is investigated. Four cell lines of different nuclear dimensions (AG1522, C3H 10T1/2, CHO-10B, and HS-23) are studied. Monte Carlo simulations are carried out to interpret the experimental results. They are presented as a function of dose to the nucleus, the total track length of alpha particles in the nucleus, and other parameters. It is found that the effectiveness of alpha particles for cell killing decreases with decreasing alpha-particle energy. The maximum RBE value is found to extend to LET values as high as 180 keV/microns. Although the LET might be the same, the effectiveness of alpha particles for cell killing is higher in the ascending part of the Bragg curve compared to descending part of the Bragg curve. The terminal tracks of alpha particles are observed to be less effective for cell killing.

Alpha Particles↗
PubMed1991

Radiobiology of alpha particles. III. Cell inactivation by alpha-particle traversals of the cell nucleus.

Cell inactivation after exposure to collimated 3.5-MeV alpha particles in three hamster cell lines, V79, CHO-10B, and HS-23, one mouse cell line, C3H 10T1/2, and a human skin fibroblast cell line were studied. Several parameters were investigated for each cell line. Theoretical calculations were performed to find the distribution of energy deposited in the nuclear volume for each cell line. The mean number of alpha-particle traversals required to induce a lethal lesion varied between two for HS-23 cells and six for C3H 10T1/2 cells. The number of traversals per unit area and the total track length of alpha particles that inactivated a cell were found to be nearly constant for the hamster and mouse cell lines. These quantities were found to be lower for the human skin fibroblast cell line. The RBE values for all cell lines were found to be about 3.8 at 10% survival. Thus cell lines that are more sensitive to alpha radiation are also more sensitive to gamma radiation. The average number of alpha-particle traversals producing a single lethal lesion is greater than one. The passages of alpha particles through the cell nucleus that do not kill the cell may lead to carcinogenic effects.

Alpha Particles↗
PubMed2006

Relative toxicity of chronic irradiation by 45Ca beta particles and 242Cm alpha particles with respect to the production of lung tumors in CBA/Ca mice.

Approximately 1800 female CBA/Ca mice were exposed by inhalation at three dose levels to beta particles from (45)Ca-labeled fused aluminosilicate particles (FAP), to alpha particles from (242)Cm-labeled FAP, or to carrier control FAP. Another group of mice inhaled no FAP and were designated as untreated cage controls. The FAP in combination with these radionuclides was used to achieve the same spatial and temporal distribution of alpha- and beta-particle dose within the irradiated mice. Some mice were killed to determine the clearance of radiolabeled FAP from their lungs, and the remainder were allocated to a life-span study. All animals were subjected to a detailed necropsy. To facilitate the identification of small tumors, the lungs were rendered transparent in methyl salicylate and examined under back illumination for the presence of lesions. Lung nodules and other microscopic lesions were excised for histological examination. The median survival of mice in all groups was approximately 910 days. The control animals lived longer than those that were irradiated, but it was difficult to determine a dose-response relationship for survival among the exposed mice. Benign adenomas and, less frequently, malignant adenocarcinomas were identified in all animal groups. The prevalence of these tumors was approximately 28.8% in the control mice, which is consistent with the results of other studies using the same strain of mouse. After exposure to radionuclide-labeled FAP, there was a significant dose-related increase in the prevalence of lung tumors in (242)Cm- (peak prevalence 55%) and (45)Ca-exposed (peak prevalence 48.6%) mice. The prevalence of tumors in the mice that received (242)Cm-labeled FAP was approximately twice that in the mice that inhaled (45)Ca-labeled FAP within the range of doses employed (0.55-4.69 Gy). Using the ratio of the slope of the linear component of the dose-response curves, the toxicity of the alpha particles relative to the beta particles was 1.5 (90% CI: 0.7, 9.0) for all adenomas and 9.4 (90% CI: 5.0, 23.0) for the less frequent adenocarcinomas. The relative toxicity for adenocarcinomas was found to decrease with increasing dose.

Adenocarcinoma↗
PubMed1991

Radiobiology of alpha particles. II. Dosimetry of low-energy alpha particles using parallel-plate ionization chambers and a surface barrier detector.

Three small parallel-plate ionization chambers were developed for measuring dose rates, of primarily low-energy alpha particles in the energy range 0.4-3.5 MeV, at a defined cell-Mylar interface. Spectral energy distributions of these alpha particles were also measured at the same position using a specially designed small-area silicon surface barrier detector. Dose rates were derived from the spectral distributions and compared with those derived from the ionization chambers. Different alpha-particle energies were obtained using a 144-MBq 238Pu collimated source and a variety of Mylar moderator foils of different thicknesses. These measurements, extended to mean alpha-particle energies as low as 0.4 MeV, will enable us to correlate radiobiological data with effects of alpha particles terminating in different regions of cell nuclei.

Alpha Particles↗
PubMed2000

A novel 210Po-based alpha-particle irradiator for radiobiological experiments with retrospective alpha-particle hit per cell determination.

A new experimental design for alpha-particle irradiation of cells in vitro is described where the alpha-particle irradiator is based on a 210Po radioactive source. In the described set-up cells are grown directly on an alpha-particle detector and irradiation is done from below. For an irradiated cell dish the number of alpha-particle traversals through each individual cell is scored by using retrospective track etch dosimetry and an accurate technique for individual cell relocation. Calibration experiments characterizing the new irradiator system are presented.

Calibration↗
PubMed1999

Alpha-particle doses to cells of the bone remodeling cycle from alpha-particle-emitting bone-seekers: indications of an antiresorptive effect of actinides.

There are indications that alpha-particle-emitting bone-seekers such as plutonium or americium could enhance bone mass by suppressing bone resorption. To assess this possibility, this study calculates doses from alpha-particle emitters to the cells involved in trabecular bone turnover. Alpha-particle energy deposition in tissue from a bone surface source was calculated by Monte Carlo modeling. This was combined with bone surface cellular geometry to yield dose rates to cells during the remodeling cycle. Bone-resorbing osteoclasts receive on average 50 times the dose rate that bone-forming osteoblasts receive. Newly formed bone shields osteoblasts from alpha particles emitted by the buried deposit of alpha-particle emitters. However, at alpha-particle bone-seeking radionuclide intakes known to cause changes in remodeling (about 3700 Bq/kg body weight), the alpha-particle dose to osteoclasts corresponds to an extremely low rate of cell traversals (0.07% per cycle). It is therefore unlikely that perturbation of bone remodeling by alpha-particle bone-seeking radionuclides is directly caused by alpha-particle traversals of remodeling cells; some other indirect mechanism might be involved.

Actinoid Series Elements↗
PubMed2000

Survival of human lung epithelial cells following in vitro alpha-particle irradiation with absolute determination of the number of alpha-particle traversals of individual cells.

PURPOSE: To throw light on human exposure to domestic radon and radon progeny, the effects of low doses of alpha-particle irradiation on normal human lung epithelial cells has been studied. At such low exposure levels the concept of dose is inadequate due to the stochastic variation in the number of alpha-particle traversals per cell. The objective of the current study was to establish an accurate survival curve for human lung epithelial cells with absolute determination of the exact number of alpha-particle traversals of individual cells. MATERIALS AND METHODS: Irradiation of L132 cells growing in tracketch detector-based cell dishes, was performed using a collimated alpha-particle beam from a 210Po source. The number of alpha-particle traversals through each individual cell was scored by using a technique of retrospective track-etch dosimetry. This technique is based upon image matching and mapping of corresponding cell and alpha-particle track images. The spatial resolution of the hit determination procedure was +/-0.9/microm. RESULTS: Surviving fractions of cells (SF) showed strict dependence on the number of nuclear traversals (n), with SF(n)= a exp(-bn), a=0.957 (+/- 0.046), b = 0.587 (+/- 0.059), R2 =98.8%. No significant dependence on the number of nuclear membrane traversals (m) or the number of cytoplasm traversals (c) was observed.

Alpha Particles↗
PubMed1991

A device for in vitro irradiation with alpha-particles using an alpha-emitting radioactive source.

A device to irradiate a monolayer of cultured cells with alpha-particles using an Am-241 alpha-source (33.4 MBq) was designed to investigate RBEs of alpha-particles in cell killing, induction of chromosome aberration, mutagenic changes and transformation. This device can be used conveniently in a common laboratory by a small number of researchers without any limitation of machine time. The device performs as follows: (1) The energy of alpha-particles at the entrance of the cell layer is 3.20 MeV with a standard deviation of 0.25 MeV, (2) the incident angle to the cell layer is 82.8 degrees with a standard deviation of 3.2 degrees, (3) the fluence rate is 4.7 x 10(5) cm-2.min-1, (4) the average LET infinity for a cell layer 5 microns thick is 138 keV/micron, (5) the average dose rate for a cell layer 5 microns thick is 0.10 Gy/min., (6) a temperature and CO2 concentration conducive to cell cultivation are maintained during irradiation.

Alpha Particles↗
PubMed2000

Computer simulation of backscattered alpha particles

Alpha-particle spectrometry forms an important aspect of radionuclide metrology. Accurate measurements require corrections to be made for factors such as self-absorption within the source and backscattering from the backing material. The theory of the latter phenomenon has only received limited attention. Furthermore the experimental verification of these theoretical results requires adequate counting statistics for a variety of sources with different activities. These problems could be resolved by computer simulations of the various interactions which occur as alpha-particles move through different materials. The pioneering work of Ziegler and his coworkers over several years, has provided the sophisticated software (SRIM) which has enabled us to obtain the results presented here. These results are compared with theoretical and experimental values obtained previously.

Journal Article↗
PubMed1988

Radioimmunotherapy with alpha-particle-emitting immunoconjugates.

Alpha particles are energetic short-range ions whose higher linear energy transfer produces extreme cytotoxicity. An alpha-particle-emitting radioimmunoconjugate consisting of a bismuth-212-labeled monoclonal immunoglobulin M specific for the murine T cell/neuroectodermal surface antigen Thy 1.2 was prepared. Analysis in vitro showed that the radioimmunoconjugate was selectively cytotoxic to a Thy 1.2+ EL-4 murine tumor cell line. Approximately three bismuth-212-labeled immunoconjugates per target cell reduced the uptake of [3H]thymidine by the EL-4 target cells to background levels. Mice inoculated intraperitoneally with EL-4 cells were cured of their ascites after intraperitoneal injection of 150 microcuries of the antigen-specific radioimmunoconjugate, suggesting a possible role for such conjugates in intracavitary cancer therapy.

Alpha Particles↗
PubMed2000

Tumor control probability model for alpha-particle-emitting radionuclides.

Alpha-particle emitters are currently being evaluated for the treatment of metastatic disease. The dosimetry of alpha-particle emitters is a challenge, however, because the stochastic patterns of energy deposition within cellular targets must be taken into account. We propose a model for the tumor control probability of alpha-particle emitters which takes into account these stochastic effects. An expression for cell survival, which is a function of the microdosimetric single-event specific-energy distribution, is multiplied by the number of cells within the tumor cluster. Poisson statistics is used to model the probability of zero surviving cells within the cluster. Based on this analysis, a number of observations have been made: (1) The dose required to eradicate a tumor is nearly a linear function of the cell survival parameter z(0). (2) Cells with smaller nuclei will require more dose to achieve the same level of tumor control probability, relative to cells with larger nuclei, for an identical source-target configuration and cell sensitivity. (3) As the targeting of alpha-particle emitters becomes more specific, the dose required to achieve a given level of tumor control decreases. (4) Additional secondary effects include cell shape and the initial alpha-particle energy.

Alpha Particles↗
PubMed2001

Rapid preparation of short-lived alpha particle emitting radioimmunopharmaceuticals.

Alpha emitting radionuclides are of considerable interest for targeted radioimmunotherapy. Generator supplied 213Bi emitting 8.5 MeV alpha particles with a 45.6 min half-life has been conjugated to a monoclonal antibody (HuM195-CHX-A-DTPA) for targeted therapy of leukemia in a clinical trial. The clinical dose preparation of pharmaceutical formulation by a pair of skilled radiochemists took 25 min, which corresponds, to an overall decay loss of 30% of the initial 213Bi activity eluted from the generator. In order to allow more widespread and practical clinical use of targeted 213Bi alpha particle therapy, we developed a new procedure that is simpler, more rapid and adaptable to a hospital pharmacy. The new 10 min process includes a tandem elution and labeling, and an anion exchange column purification method that can be reproducibly used.

Alpha Particles↗
PubMed1999

Fetal dosimetry from natural alpha-particle emitters.

The alpha-particle dose to human fetal bone marrow from natural exposure was investigated. The rate of calcification and the (210)Pb activity levels in fetal vertebrae showed that (210)Pb follows the uptake of calcium into the skeleton. Lead-210-supported (210)Po activity concentrations of up to 0.18 Bq kg(-1) were found in fetal lumbar vertebra. The mean chord length of the trabecular spaces in lumbar vertebra were 110-320 micrometer at 20- 40 weeks, in rib 130-180 micrometer at 20-35 weeks, and in sternum 190 micrometer at 35 weeks of gestation. In lumbar vertebra, up to 80% of marrow was within alpha-particle range (37 micrometer) of a bone surface. This resulted in a gestational equivalent dose to marrow from (210)Pb-supported (210)Po in bone of 8 and 24 micrometerSv when the contribution from all major natural alpha-particle-emitting radionuclides was considered. The mean distance of CD34(+) cells from the nearest bone surfaces in lumbar vertebra was 61 and 46 micrometer at mid- and late gestation, respectively. The mean cellular and nuclear diameters of CD34(+) cells were 5.5 and 3.8 micrometer respectively, and remained constant with gestational age. Few stem cells were hit by alpha particles at natural exposure; however, those that were hit received doses of up to 1.3 Gy.

Alpha Particles↗
PubMed1997

Dosimetric framework for therapeutic alpha-particle emitters.

UNLABELLED: Alpha-particle emitters are currently being considered for the treatment of metastatic disease. However, the dosimetry of alpha-particle emitters is a challenge because the dimensions of subcellular targets (e.g., the cell nucleus) are of the same order of magnitude as the range of the particle. Hence, a single dose value is often not representative of the dose delivered to a cell population. Here, we propose a dosimetry system that combines the calculational ease of the Medical Internal Radiation Dosimetry (MIRD) system with the additional information provided by microdosimetry. METHODS: Beginning with the microdosimetric, single-event specific-energy spectrum, we derived expressions for the first and second moments. Using the MIRD S-factor along with these moments, we determined not only the mean absorbed dose but also the s.d. and the fraction of cells receiving zero (or any number of) hits. RESULTS: Using the formalism developed here, we have generated tables for a simple example to demonstrate the use of this method. CONCLUSION: We have developed a formalism for the rapid determination of not only the mean absorbed dose but also the s.d. and fraction of cells receiving zero hits. These parameters are potentially useful in analyzing the biological outcome for cells exposed to alpha-particle irradiation.

Alpha Particles↗
PubMed1996

Induction of genomic instability in normal human bronchial epithelial cells by 238Pu alpha-particles.

Pulmonary deposition of alpha-particle-emitting radon daughters is estimated to account for 10% of all lung cancer deaths in the USA. However, the nature and timing of early (preneoplastic) genetic alterations in radon-associated lung cancer are still relatively uncertain. The purpose of this investigation was to determine whether genomic instability occurs after exposure of cultured normal human bronchial epithelial cells to six equal, fractionated doses of alpha-particles (total doses 2-4 Gy). Two weeks after the final exposure, foci of phenotypically altered cells (PACs) were detected in 0, 63 and 77% of control, low and high dose cultures respectively. Of these, 18% exhibited extended life spans relative to unexposed controls. Elevated frequencies of binucleated cells (BNCs), a marker of genomic instability, were observed in 60 and 38% of the PAC cultures from the low and high dose groups respectively. The micronucleus assay also showed evidence of genomic instability in 40 and 38% of PAC cultures from the low dose and high dose groups respectively. No changes in microsatellite length, another marker of genomic instability, were detected in any of the PAC samples with the 28 markers used for this assay. However, one PAC (L2) showed a hemizygous deletion at 9p13.3. Another PAC (H9), which exhibited the highest frequency of cells containing micronuclei (MN), exhibited a hemizygous deletion at 7q31.3. Each loss may represent a stable mutation that resulted either directly from irradiation or later in progeny of exposed cells because of alpha-particle-induced genomic instability. The fact that elevated levels of BNCs and MN were present in the progeny many generations after irradiation indicates that the genetic alterations detected with these two markers were not a direct consequence of radiation exposure, but of resulting genomic instability, which may be an early change after exposure to alpha-particles.

Adolescent↗