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Track nanodosimetry of an alpha particle.

Experimental measurements and calculations are described of ionisation distributions in propane wall-less gas cavities of about 20 nm simulated size, performed at different distances from a 244Cm alpha particle track. Ionisation events are detected one by one by collecting electrons from the sensitive volume and by separating them with a drift column. Experimental results and Monte Carlo calculations indicate that, in the delta ray cloud, conditional probability curves, average cluster size and the ratio of second moment above first moment of the cluster distribution are invariant with track distance.

Alpha Particles↗

Collision efficiency factor of bubble and particle (alpha bp) in DAF: theory and experimental verification.

The collision efficiency factor of bubble and particle (alpha bp) in dissolved air flotation (DAF) can be calculated theoretically by trajectory analysis, which takes into account both hydrodynamics and interparticle forces. To determine the theoretically optimum particle size for any given bubble size, a collision efficiency diagram for DAF was developed where collision efficiency is contoured on a plane of particle and bubble sizes for different conditions of particle zeta potential. A set of experiments tested the validity of the suggested collision efficiency diagram, and examined whether pretreatment is important and why slight coagulant overdosing and shorter flocculation times are generally preferred in DAF, both current accepted practice. Batch DAF reactors were used and kaolin samples were prepared from jar tests using different alum dosages and flocculation times. The particle size distribution, particle zeta potential, and turbidity removal in each experiment were measured, as were bubble size and zeta potential. The results agreed well with the predictions of the collision efficiency diagram and explained current practices. A collision efficiency diagram identifies the pretreatment goal, i.e., tailoring of the optimum characteristics required of particles (zeta potential and size) under existing operational bubble characteristic.

Air↗

Labeling monoclonal antibodies and F(ab')2 fragments with the alpha-particle-emitting nuclide astatine-211: preservation of immunoreactivity and in vivo localizing capacity.

alpha-Particles such as those emitted by 211At may be advantageous for radioimmunotherapy since they are radiation of high linear energy transfer, depositing high energy over a short distance. Here we describe a strategy for labeling monoclonal antibodies and F(ab')2 fragments with 211At by means of the bifunctional reagent N-succinimidyl 3-(trimethylstannyl)benzoate. An intact antibody, 81C6, and the F(ab')2 fragment of Me1-14 (both reactive with human gliomas) were labeled with 211At in high yield and with a specific activity of up to 4 mCi/mg in a time frame compatible with the 7.2-hr half-life of 211At. Quantitative in vivo binding assays demonstrated that radioastatination was accomplished with maintenance of high specific binding and affinity. Comparison of the biodistribution of 211At-labeled Me1-14 F(ab')2 to that of a nonspecific antibody fragment labeled with 211At and 131I in athymic mice bearing D-54 MG human glioma xenografts demonstrated selective and specific targeting of 211At-labeled antibody in this human tumor model.

Animals↗

Cytogenetic and molecular genetic analysis of tumorigenic human bronchial epithelial cells induced by radon alpha particles.

To establish a cell culture model for lung carcinogenesis, independent populations of the human papillomavirus 18-immortalized human bronchial epithelial cell line BEP2D were treated with high linear energy transfer radon-simulated alpha-particles, expanded and xenotransplanted into Nu/Nu mice. Six independent cell lines were established from tumors that developed from three separate radiation treatments as follows: treatment (Tx) 1 (30 cGy--two doses), H2BT, Tx 2 (30 cGy--single dose), R30T1L, R30T2 and R30T3L, Tx 3 (30 cGy--single dose), H1ATN and H1ATBA1. Cytogenetic analysis revealed common changes in all tumor lines: loss of the Y chromosome (ch), one of three copies of ch8, one of three copies of ch14, and one of two copies of ch4p16-pter and ch11p15-pter. Analysis of polymerase chain reaction-amplified short tandem repeats of informative loci confirmed the loss of chY in all lines and loss of heterozygosity (LOH) at eight loci spanning the length of ch8 in all lines from Tx's 1 and 2. Our data support previous studies indicating the presence of tumor suppressor genes on ch8. LOH also was confirmed on ch14 at locus D14S306 in all cell lines from Tx 2 and in one of two lines from Tx 3. This region, 14q12-q13, may contain changes in one of the five known somatostatin receptor genes (SSTR1). No LOH was detected at any of the informative loci tested for on ch4 or ch11.

Alpha Particles↗

Efficiency estimation for detecting U alpha particles in solid-state nuclear track detectors.

The detection efficiencies of solid-state nuclear track detectors, made with cellulose nitrate materials (LR-115 II) or allyl diglycol carbonate (CR-39) were investigated. Detection efficiency for a surface alpha source was experimentally obtained by changing the dimensions between the detector and the source, while alpha-particle incident efficiency was calculated. The ratio of the detection efficiency to the incident efficiency was then determined. It was confirmed that the ratio for LR-115 II was dependent on energy, but for CR-39 the ratio showed almost no dependency. Considering the relationship between solid absorber thickness and detection efficiency of the surface alpha source, detection efficiencies of U in various metals were estimated. The efficiency for U contained in Al and Fe was proposed as 16% for LR-115 II and 22% for CR-39. Using these efficiencies, amounts of U in some Al and Fe ingots were determined. These agreed with concentrations obtained by neutron-activation analysis with deviations of less than 15%.

Alpha Particles↗

Alpha-particle dosimetry for the basal layer of the skin and the radon progeny 218-Po and 214-Po.

The population average dose to the basal layer of the skin is evaluated, in terms of dose per alpha-particle decay per unit area, for radon progeny 218-Po and 214-Po attached to the skin surface. Account is taken of the variation in basal layer depth between different individuals, and results are presented for several anatomical regions. On the face, for example, the population average dose to the basal layer from 218-Po is of the order of 0.5 microSv/decay/cm2 while that from 214-Po is of the order of 1 microSv/decay/cm2. Radiation induced stochastic effects in the skin are generally assumed to originate from target cells located in the basal layer. Provided this assumption is correct, these results suggest that both 218-Po and 214-Po could be regarded as potential carcinogenic agents for the induction of skin cancer.

Alpha Particles↗

Contribution from the inner shell of water vapour to dose profiles under proton and alpha particle irradiation.

Doubly differential cross sections for electron emission calculated using the CDW-EIS model and a simple approximation for the electron transport in the target are used to obtain dose profiles around the ion path for proton and alpha particles in water vapour. The contribution from each initial molecular orbital is determined. At large distances from the track, discrepancies are found with other models and with the well known r-2 dependence.

Alpha Particles↗

The effect of alpha particles on bacteriophage T4Br+.

It is generally accepted that heavy charged particles play an important part in generating the secondary flux of nuclear particles formed by the interaction of space hadrons with nuclei. It is assumed that these particles are responsible for the high biological efficiency of space hadrons in causing cellular damage by their strong interactions. To examine this assumption we investigated the effects of 5.3 MeV alpha particles on bacteriophage T4. This energy provides a LET value of 88.6 KeV/micrometer lying in the range of the highest biological efficiency.

Alpha Particles↗

Lack of detectable transmissible chromosomal instability after in vivo or in vitro exposure of mouse bone marrow cells to 224Ra alpha particles.

Several studies over recent years have highlighted the possibility that radiation can induce transmissible genomic instability. Most of these involve in vitro irradiation and usually in vitro culture. Here it is reported that the short-half-life bone-seeking alpha-particle emitter (224)Ra did not induce excess transmissible chromosomal instability in CBA/H mouse bone marrow cells in a 100-day period after in vivo or in vitro exposure. Similarly, no excess transmissible chromosomal instability could be detected after in vivo whole-body X irradiation. It was noted, however, that short-term culture of murine bone marrow cells elevated yields of aberrations, as did transplantation of untreated marrow into radiation-ablated hosts. These findings emphasize the sensitivity of murine hemopoietic tissue to experimental manipulation and reinforce the importance of appropriate concurrent control experiments in any investigation of transmissible genomic instability.

Alpha Particles↗

Direct evidence for the participation of gap junction-mediated intercellular communication in the transmission of damage signals from alpha -particle irradiated to nonirradiated cells.

It has generally been considered that important biological effects of ionizing radiation arise as a direct consequence of DNA damage occurring in irradiated cells. We have examined this hypothesis by exposing cells to very low fluences of alpha-particles, similar to those emitted by radon gas, such that as few as 1% of the cells in a population are traversed by a particle and thus receive any radiation exposure. By using the endpoints of changes in gene expression and induction of DNA damage, we show that nonirradiated "bystander" cells participate in the overall response of confluent density-inhibited populations of cultured fibroblast and epithelial cells. By in situ immunofluorescence techniques and the use of cells genetically compromised in their ability to perform gap junction intercellular communication, we present direct evidence for the involvement of connexin43-mediated intercellular communication in the transmission of damage signals to nonirradiated cells. Induction of the stress-inducible p21(Waf1) protein in aggregates of neighboring cells far exceeding the fraction of cells whose nucleus has been traversed occurred in gap junction-competent cells only. These changes in p21(Waf1) expression correlated with both the induction of DNA damage (as measured by micronucleus formation) as well as increased Ser-15 phosphorylation of p53.

Alpha Particles↗

Proteome analysis on an early transformed human bronchial epithelial cell line, BEP2D, after alpha-particle irradiation.

To probe the mechanism of carcinogenesis of lung cancer at the molecular level and to find potential protein markers involved in the early phase of tumorgenesis, differential proteome analysis on primary passage cell line R15H, and early transformed cell line R15H20 derived from (238)Pu alpha-particle irradiation of human papillomavirus (HPV) 18-immortalized human bronchial epithelial cell line (BEP2D), was carried out using two-dimensional electrophoresis (2-DE) and peptide mass fingerprinting (PMF) with matrix-assisted laser desorption/ionisation-time of flight mass spectrometry. Image analysis and Student's t-test (p < 0.05) showed that three protein spots were only expressed in R15H, intensities of 43 protein spots on the gels were altered between R15H and R15H20. Two of the three spots that were only expressed in R15H were identified as high mobility group protein 1. Two proteins decreased in abundance in R15H20 were identified as maspin precursor, a tumor suppressor and aminoacylase-1. Ornithine aminotransferase and peptidyl-prolyl cis-trans isomerase A that were increased in R15H20, were also identified. Relationships between these differentially expressed proteins and the carcinogenesis mechanism of lung cancer are discussed. The protein expression profile of the R15H cell line was also constructed during the study as a reference map for further comparative proteome analysis of the irradiation induced BEP2D cell line. Of the 90 spots analyzed with PMF in the 2-DE gel of R15H cell line, 50 proteins were identified by searching the nonredundant protein database SWISS-PROT/TrEMBL.

Alpha Particles↗

Cytogenetic effects of protracted exposures to alpha-particles from plutonium-239 and to gamma-rays from cobalt-60 compared in male mice.

Adult C3H X 101 hybrid male mice were injected intravenously with 4 muCi of 239Pu citrate per kg body weight and examined for evidence of cytogenetic damage to the testis after exposures of 21, 28 and 34 weeks, with average doses from alpha-particles estimated as 13, 18 and 18 rad respectively (mean dose rate 0.00006 rad/min). Results were compared with those obtained when equivalent males were exposed continuously and concurrently to 1128 rad 60Co gamma-irradiation over 28 weeks (0.004 rad/min). The following estimates of the relative effectiveness of the alpha- and gamma-radiation were made: 24 for reciprocal translocations and for chromosome fragments, 22 for dominant lethal mutations acting after implantation. These values (with mean of 23) are based on average testis doses, with no correction for probable non-homogeneity of alpha dose distribution. In the mice exposed to gamma-irradiation there were significant reductions in testis mass and epididymal sperm-count. Although corresponding differences from control were not significant in the alpha series, consideration of results from a previous experiment by the same authors [2] allowed the relative effectiveness of the alpha- and gamma-irradiation for testis mass reduction to be estimated as roughly 10-15. Existing data on translocation induction in mouse spermatogonia by low dose-rates of gamma-rays (down to 0.003 rad/min) were analysed. They suggested that minimum rates of induction at very low intensities were not less than 1 X 10(-5) translocations per rad. A comparison of the frequencies of induction of fragments and of sperm-head abnormalities obtained after chronic gamma-ray exposures in the present experiment with those found by other workers after acute X-ray exposures suggested that there were no marked dose-rate effects with these types of mutational effect. Finally, the special problems associated with cytogenetic studies on alpha-emitters are discussed.

Alpha Particles↗

Comparison of the stopping cross-sections of ethylene and polyethylene using alpha particles in the energy range 1.5--4.2 MeV.

In order to design reliable gas-filled dosemeters it is necessary to have knowledge of the ratios of the stopping powers of various solids and their gaseous equivalents. This paper describes the measurement of the stopping cross-sections of ethylene and its polymer polyethylene using alpha particles, and compares the measurements with results published by other workers. The results indicate that there is no difference between the two sets of values, within the quoted errors. Reasons are suggested to account for part of the discrepancy between our results and those of others for thin solid sample measurements.

Alpha Particles↗

The biological effectiveness of radon-progeny alpha particles. II. Oncogenic transformation as a function of linear energy transfer.

Epidemiological studies have established an association between exposure to radon and carcinoma of the lung. However, based on data for either lung cancer in uranium miners exposed to radon or bronchial epithelial carcinomas in Japanese A-bomb survivors, it has not been possible to assign estimates of risk of lung cancer for the general population exposed to radon in their homes. Based on past success with the excellent quantitative properties of the C3H 10T1/2 in vitro oncogenic transformation assay system, the relative biological effectiveness (RBE) for radiation-induced transformation for charged particles of defined LET has been determined. As the LET of the radiation was increased, the rate of induction of oncogenic transformation increased and the RBEm approached 20. At higher LETs, RBE dropped precipitously. The rapid drop in effectiveness for alpha particles with LETs between 120 and 265 keV/microns implies a lower quality factor than the 20-25 currently considered appropriate when estimating lung cancer mortality.

Alpha Particles↗

Microdosimetry of rat alveolar type II cells irradiated with alpha particles from 239PuO2.

The alveolar type II cell is one of the critical cells for radiation damage in the lungs after inhalation of radioactive aerosols. With the aid of a Quantimet-970 image analyzer and a VAX-11/780 computer, we calculated the radiation dose to rat alveolar type II cells from alpha particles emitted by 239PuO2. A series of dosimetric parameters for type II cells, including track length distribution, linear energy transfer (LET), values of the specific energy for a single hit of a spherical target (z1), cellular dose, hit number, and their spatial distributions were calculated. By comparing the volume density of type II cells and lung tissue with energy deposited in alveolar type II cells, we found that the energy deposited per unit volume of type II cells was larger than that of lung tissue excluding type II cells. The z1 for spherical targets and the LET across type II cells were less than those in lung tissue excluding type II cells. The age of the rat and damage to lung by inhalation may significantly influence some of the parameters. The neoplastic transformation probability for type II cells is also discussed. The results suggest that the type II cell is an important target cell in the rat lung for exposure to inhaled 239PuO2.

Aerosols↗

Radioimmunotherapy with alpha-particle emitters: microdosimetry of cells with a heterogeneous antigen expression and with various diameters of cells and nuclei.

Intercellular variations in the level of antigen expression and in cellular and nuclear radii were taken into account in a model used to estimate cell survival for an in vitro experiment with antibodies containing alpha-particle emitters that target the cell surface. Using measured variations in these characteristics for cells of two human cancer cell lines, the model gave results for cell survival and the fundamental parameter of radiation sensitivity, z(0), that differ substantially from those obtained using only mean values. The cell survival may be underestimated by a factor of 100 if only mean values of these cellular parameters are used, and calculated values of z(0) may be overestimated by a factor of 2. Most of this effect stems from the variation in antigen expression. The magnitudes of the differences were found to be a function of the fractions of mean specific energy delivered by surrounding activity and by activity bound to the cells.

Alpha Particles↗