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[Effect of single alpha-particle on cells].

The mechanisms of biological effect of charged particles in space was studied through the inactivation effect of very low-density charged particles on very low-density cells at different impact parameters. A small type of microbeam facility with alpha-radioactive source and CN track detector were used. A diploid wild type Saccharomyces cerevisiae served as experimental eukaryotic cell. The correlation between cell inactivation and impact parameter of alpha-particles on cells was obtained through a CCD-camera system. The results showed that inactivation range of 1.13 MeV/u alpha-particles on cell-agarose mixture was about 5.5 micrometers, larger than the sum (about 3.l micrometers) of ion track-penumbra radius and yeast cell radius. The cell inactivation rate was 0.36-0.33. It suggests that multi-hit on a cell is necessary for killing it. However, in case of miss, the inactivation rate may not be zero at certain impact parameters.

Alpha Particles↗

Direct comparison of biological effectiveness of protons and alpha-particles of the same LET. II. Mutation induction at the HPRT locus in V79 cells.

Mutation induction at the hprt locus has been studied in V79-4 Chinese hamster cells irradiated with mono-energetic protons and alpha-particles with LET of 20.3 and 23 keV microns-1. The mutation frequency increased linearly with the dose for all the four radiation qualities investigated, so that effectiveness for mutation induction could be expressed by the slope of the relevant curve. This effectiveness did not significantly change with the small change in LET of each kind of particle, while sizeable differences were found between particles. Protons were more effective in mutation induction than alpha-particles with the same LET by a factor of about 2. This finding is similar to, although slightly larger than, the factors 1.5-1.8 found for inactivation of the same cells in the same series of experiments.

Alpha Particles↗

Observation of the alpha particle "Knock-On" neutron emission from magnetically confined DT fusion plasmas

Suprathermal fuel ions from alpha-particle knock-on collisions in fusion DT plasmas are predicted to cause a weak feature in the neutron spectrum of d+t-->alpha+n. The knock-on feature has been searched for in the neutron emission of high ( >1 MW) fusion-power plasmas produced at JET and was found using a magnetic proton recoil type neutron spectrometer of high performance. Measurement and predictions agree both in absolute amplitude and in plasma-parameter dependence, supporting the interpretation and model. Moreover, the results provide input to projecting alpha-particle diagnostics for future self-heated fusion plasmas.

Journal Article↗

Design of a benchtop alpha particle irradiator.

The design, construction and calibration of a convenient irradiator is described that provides controlled exposure to a uniform external source of well-characterized alpha particles at a dose-rate of 0.99 cGy min-1. The use of a precis- ion photographic shutter allows the accurate delivery of doses as low as 0.01 mGy (1 mrad) to cultured cells. Special features also include a helium environment and reciprocal collimator that permits the use of collimators with different transmission factors to achieve differing dose-rates. A simple method is described to characterize the energy spectrum of alpha particles by use of particle range as measured by track etch.

Alpha Particles↗

Modern nuclear force predictions for the alpha particle

We present new calculations of the alpha particle which are based on the most modern nucleon-nucleon interactions alone and combined with the Tucson-Melbourne or the Urbana IX three-nucleon interaction. Results for the binding energies and some properties of the wave function are given. On that phenomenological level little room is left for the action of a possible four-nucleon force.

Journal Article↗

Spindle checkpoint and apoptotic response in alpha-particle transformed human bronchial epithelial cells.

The mitotic spindle checkpoint and apoptosis in response to nocodazole, a microtubule-disrupting agent, were investigated in the alpha-particle transformed human bronchial epithelial cell lines BERP35T1, BERP35T4 and the parental BEP2D cell line. When treated with 0.2 microg/ml of nocodazole, BEP2D and BERP35T1 cells were efficiently arrested in the mitotic phase, whilst BERP35T4, a transformed cell line showing chromosomal instability, failed to be arrested as evidenced by a low G2/M fraction. BERP35T4 cells also showed a higher proportion of aneuploids when treated with nocodazole or not. Thus, the BERP35T4 cell line has a defect in spindle checkpoint function. The extent of apoptosis induced by nocodazole (0.3 microg/ml) was significantly higher (2-fold to 2.5-fold) in BEP2D cells than in the two transformed cell lines. Furthermore, the induced apoptosis was found to occur predominantly before mitotic division in BEP2D cells. In BERP35T4 cells, however, 50% of induced apoptosis occurred before mitotic division and 50% occurred after division in binucleated cells when co-treated with cytochalasin B. The 5'-CpG island of the Chfr gene, a mitotic checkpoint gene that functions in entry into metaphase, was found to be methylated in BERP35T4 cells but not in BEP2D cells. Consistent with methylation, the expression of the Chfr gene was markedly suppressed in BERP35T4 cells. Our results suggest that the impaired spindle checkpoint and abnormal apoptotic response may be related to the oncogenic progression of human bronchial epithelial cells initiated by exposure to alpha-particles.

Alpha Particles↗

Monte Carlo/numerical treatment of alpha-particle spectra from sources buried in bone and resultant doses to surface cells.

PURPOSE: To calculate the depth distribution of radioactive decays in bone by fitting a calculated alpha-particle energy spectrum to a measured spectrum. The dose to bone surface cells is then calculated from the depth distribution. MATERIALS AND METHODS: The spectra are calculated using Monte Carlo methods and a numerical depth distribution obtained by trial and error. RESULTS: Alpha spectra for 210Po and 226Ra (plus decay products) in bone were calculated and fitted to experimental spectra. The dose to bone surface cells was calculated using the numerical technique and compared to previously published data. CONCLUSIONS: Alpha-particle spectra can be successful fitted using this method, which gives a more realistic distribution of decays with depth than simple surface and volume models.

Alpha Particles↗

Dose-effect relationship of chromosome aberrations induced by 23 MeV alpha particles in human lymphocytes.

The dose-effect relationship and intercellular distribution of chromosome aberrations were studied in human peripheral blood lymphocytes irradiated in vitro with 23 MeV alpha particles. The frequency of dicentrics, mu, was best expressed by a linear-quadratic model, mu = 7.55 X 10(-1) D + 2.1 X 10(-2) D2, although the dose-quadratic component was not significantly different from zero giving a fit to a linear model mu = 7.93 X 10(-1) D also (D in Gy). The intercellular distributions of dicentrics were over-dispersed compared with Poisson distribution, and the dispersion index as expressed by the relative variance increased with the increase of mean dicentric yield. Stochastic considerations based on the relative variance indicated the presence of inter-track interaction in the formation of dicentrics by alpha particles. Modification of the dose-response relationship by selective loss of cells with more damage is discussed.

Adult↗

Alpha particles initiate biological production of superoxide anions and hydrogen peroxide in human cells.

The mechanism(s) by which high-linear energy transfer a particles, like those emitted by inhaled radon and radon daughters, cause lung cancer has not been elucidated. Conceivably, DNA damage that is induced by a particles may be mediated by the metabolic generation of reactive oxygen species (ROS), in addition to direct a particle-DNA interactions and hydroxyl radical-DNA interactions. Using normal human lung fibroblasts, we investigated the hypothesis that densely ionizing alpha particles may induce the intracellular generation of superoxide (O2.-) and hydrogen peroxide (H2O2). Ethidium bromide and 2',7'-dichlorofluorescein, fluorescent products of the membrane-permeable dyes hydroethidine and 2',7'-dichlorofluorescin diacetate, respectively, were used to monitor the intracellular production of O2.- and H2O2, respectively, by flow cytometry. Compared to sham-irradiated cells, fibroblasts that were exposed to alpha particles (0.4-19 cGy) had significant increases in intracellular O2.- production, along with concomitant increases in H2O2 production. Further analyses suggest that the plasma membrane-bound NADPH-oxidase is primarily responsible for this increased intracellular generation of ROS and that the ROS response does not require direct nuclear or cellular "hits" by the a particles. In this latter regard, we additionally report that unirradiated cells also show the ROS response when they are incubated with serum-containing culture medium that has been exposed to a particles or when they are incubated with supernatants from a-irradiated cells. Our overall results support the possibility that a particles, at least in part, may mediate their DNA-damaging effects indirectly via a ROS-related mechanism.

Alpha Particles↗

Evaluation of internal alpha-particle radiation exposure and subsequent fertility among a cohort of women formerly employed in the radium dial industry.

This study examined the effect of internal exposure to alpha-particle radiation on subsequent fertility among women employed in the radium dial industry prior to 1930, when appreciable amounts of radium were often ingested through the practice of pointing the paint brush with the lips. The analysis was limited to women for whom a radium body burden measurement had been obtained and who were married prior to age 45 (n = 603). Internal radiation dose to the ovary was calculated based on initial intakes of radium-226 and radium-228, average ovarian mass, number and energy of alpha particles emitted, fraction of energy absorbed within the ovary, effective retention integrals and estimated photon irradiation. Time between marriage and pregnancy, number of pregnancies and number of live births served as surrogates for fertility. Radiation appeared to have no effect on fertility at estimated cumulative ovarian dose equivalents below 5 Sv; above this dose, however, statistically significant declines in both number of pregnancies and live births were observed. These trends persisted after multivariable adjustment for potential confounding variables and after exclusion of subjects contributing a potential classification or selection bias to the study. Additionally, the high-dose group experienced fewer live births than would have been expected based on population rates. There were no differences in time to first pregnancy between high- and low-dose groups. These results are consistent with earlier studies of gamma-ray exposures and suggest that exposure to high doses of radiation from internally deposited radium reduces fertility rather than inducing sterility.

Abortion, Spontaneous↗

Stopping cross-sections of various gases for alpha particles in the energy region 0.2 to 5.5 MeV.

A single experimental apparatus has been designed to allow measurements of stopping cross-sections of materials in liquid and vapour phase, for alpha particles, using an indirect method. The method, in which residual energies for increasing absorber thicknesses are obtained and differentiated, has been used in a number of investigations of phase effects in stopping power. As a set of preliminary experiments, the stopping cross-sections of He, N2, Ar, CH4 and air for alpha particles have been measured, to allow overall assessment of measurement and data analysis procedures by comparison with other published results. Such comparison suggests that the absolute uncertainty of the techniques employed in unlikely to exceed 4 or 5%. Some of the problems associated with indirect measurements of stopping power are discussed.

Air↗

Effects of 210Po alpha particles on survival and preneoplastic transformation of primary rat tracheal epithelial cells irradiated while in suspension or in the intact tissue.

Rat tracheal epithelial cells exhibited exponential cell killing when exposed to 210Po alpha particles as single cell suspensions or in the intact tissue. Survival of cells in the intact tissue was not significantly different from that observed with cell suspensions. Comparison of survival of cells exposed in suspension to 300 kVpX rays yielded an RBE of 6.3. Measurements of basal cell nuclei were used to determine that a single traversal of a cell nucleus had a high probability of causing cell inactivation. This was also observed in mink lung cells and CHO cells exposed in an identical manner. There were no significant increases in frequencies of preneoplastic transformation observed for a range of exposures (0.0007 to 0.05 alpha particles/micron2). Examination of intact tracheal transplants which were irradiated with alpha particles also failed to reveal any preneoplastic or neoplastic changes.

Alpha Particles↗

Comparison of the radiotoxicity of two alpha-particle-emitting immunoconjugates, terbium-149 and bismuth-213, directed against a tumor-specific, exon 9 deleted (d9) E-cadherin adhesion protein.

We investigated the effects of the alpha-particle emitters (149)Tb and (213)Bi coupled to a tumor-specific antibody targeting the mutated delta 9 E-cadherin (d9 E-Cad) on single cells and cell pellets. The d9 mutation of the adhesion molecule E-cadherin is found in 10% of diffuse-type gastric cancers and is not expressed in normal tissue. Human breast cancer cells (MDA-MB-435S) transfected with d9 E-Cad or the wild-type E-cadherin gene were used to study the effects of anti-d9 E-Cad MAb coupled to (149)Tb and (213)Bi ((149)Tb-d9 MAb and (213)Bi-d9 MAb). The density of binding sites determined on transfected MDA tumor cells by Scatchard analysis and flow cytometry varied from 4 x 10(4) to 6 x 10(4) antigens per cell. Internalization of radioimmunoconjugates by cells expressing d9 E-Cad was less than 10% of bound antibody within 240 min. The effect of the radioimmunoconjugates on cell suspensions and cell pellets was quantified by [(3)H]thymidine incorporation, and the dose to the cell nuclei was determined using microdosimetric calculations. (149)Tb and (213)Bi immunoconjugates affected cells in suspension similarly. Significant differences in the proliferation capacity of d9 E-cadherin- and wild-type E-cadherin-expressing cells were observed at activity concentrations around 185 kBq/ml, corresponding to antibody concentrations between 200 ng/ml and 1000 ng/ml. Proliferation after incubation with (213)Bi-d9 MAb was 50% greater in pelleted wild-type E-Cad-expressing cells compared to wild-type E-Cad cells in suspension. In contrast, the proliferation of pelleted d9 E-Cad cells was similar to that of d9 E-Cad cells in suspension. For (149)Tb-d9 MAb, no significant difference was found between pelleted cells and cells in suspension for low activity concentrations. However, at high activity concentrations, (149)Tb-d9 MAb had only a small effect on pelleted cells. These in vitro studies demonstrate different effects of (149)Tb and (213)Bi conjugated to a tumor-specific antibody toward single cells and tumor cell pellets. Microdosimetric simulation of single cell survival after alpha-particle irradiation modeled the experimental results with reasonable accuracy.

Alpha Particles↗

Alpha-particle irradiation-induced change in bronchopulmonary macrophage morphology, in vitro.

Bronchopulmonary macrophages, isolated from canine lungs by saline lavage and grown in tissue culture for short periods, were acutely irradiated with a range of doses of either Americium-241 alpha particles (0.03-48 Gy) or 250 keV x-rays (0.5-24 Gy). Following a 24-hour reincubation and "expression" period, cells were examined for radiation-induced changes in overall viability, as well as in cell morphology and ultrastructure. Results indicated that neither quality of radiation had much effect on cell viability over dose ranges examined, but substantial changes in cell volume, surface topography, and cytoplasmic features were noted, especially in the alpha-particle-irradiated specimens. Results support the concept that the limiting plasma membrane of the targeted macrophage is a sensitive subcellular target for ionizing radiation, especially high-linear-energy-transfer heavy particles.

Alpha Particles↗

Lethality and mutagenesis of B lymphocyte progenitor cells following exposure to alpha-particles and X-rays.

B lymphocyte precursor cells are the target cells for the major subtype of paediatric cancer, acute lymphoblastic leukaemia. Using a murine IL-7-dependent clonogenic assay for normal B cell precursors as a model, we have investigated the sensitivity of these cells versus other normal and leukaemic haemopoietic cells to alpha-particle radiation. We find that B cell precursors are remarkably susceptible to the lethal effects of alpha-particles and have a very low probability of surviving a single alpha-track. B cell precursors are also very sensitive to the lethal effects of low LET X-rays. The mutation frequency in a marker gene (HPRT) does not, however, appear to be greater in B cell precursors that survive X-radiation than in other haemopoietic cells.

Alpha Particles↗

Absorbed fraction of alpha-particles emitted in bifurcation regions of the human tracheo-bronchial tree.

A model for bifurcation regions of the human tracheo-bronchial tree was developed. Equations for the surfaces are given to enable calculations of doses from alpha-particles emitted in these regions. It has been found that a bifurcation region is well approximated by a quasi-ellipsoid. The absorbed fractions of alpha-particles emitted in bifurcation regions were calculated by the Monte Carlo method. The average absorbed fraction under the bifurcation geometry is close to that found under the cylindrical geometry in the bronchial region. In the bronchiolar region, the absorbed fractions under the bifurcation geometry are up to 20% larger than those under the cylindrical geometry.

Air Pollutants, Radioactive↗

The track structure of alpha-particles from the point of view of ionization-cluster formation in "nanometric" volumes of nitrogen.

Probability distributions of the size of ion clusters created in "nanometric" volumes of nitrogen by single alpha-particles of a gold-plated 241Am source, were measured and compared with those calculated by Monte Carlo methods in the same geometry. The diameter of the sensitive volumes had a mass per area of between 0.015 microgram/cm2 and 1.3 micrograms/cm2 which, for a material at unit density, corresponds to a nanometric target volume 0.15-13 nm in diameter. These nanometre sizes were simulated experimentally in a device called the Jet Counter. This consists of a pulse-operated valve which injects into an interaction chamber an expansion jet of molecular nitrogen gas, which is crossed by a narrow beam of alpha-particles. The resulting ions are counted and analyzed from the point of view of ionization cluster formation. The measured or calculated cluster size probabilities prove that the formation of ionization clusters along a "nanometre" track is governed by Poisson's law only in the case of very small target volumes, due to the contributions by secondary electrons. The present ionization cluster probabilities produced in "nanometric" volumes 0.15-13 nm in diameter, are the first ever determined experimentally and confirmed by Monte Carlo simulation.

Alpha Particles↗

A study of endonuclease III-sensitive sites in irradiated DNA: detection of alpha-particle-induced oxidative damage.

An important difference between chemical agents that induce oxidative damage in DNA and ionizing radiation is that radiation-induced damage is clustered locally on the DNA. Both modelling and experimental studies have predicted the importance of clustering of lesions induced by ionizing radiation and its dependence on radiation quality. With increasing linear energy transfer, it is predicted that complex lesions will be formed within 1-20 bp regions of the DNA. As well as strand breaks, these sites may contain multiple damaged bases. We have compared the yields of single strand breaks (ssb) and double strand breaks (dsb) along with those produced by treatment of irradiated DNA with the enzyme endonuclease III, which recognizes a number of oxidized pyrimidines in DNA and converts them to strand breaks. Plasmid DNA was irradiated under two different scavenging conditions to test the involvement of OH* radicals with either 60Co gamma-rays or alpha-particles from a 238Pu source. Under low scavenging conditions (10 mM Tris) gamma-irradiation induced 7.1 x 10(-7) ssb Gy/bp, which increased 3.7-fold to 2.6 x 10(-6) ssb Gy/bp with endo III treatment. In contrast the yields of dsb increased by 4.2-fold from 1.5 x 10(-8) to 6.3 x 10(-8) dsb Gy/bp. This equates to an additional 2.5% of the endo III-sensitive sites being converted to dsb on enzyme treatment. For alpha-particles this increased to 9%. Given that endo III sensitive sites may only constitute approximately 40% of the base lesions induced in DNA, this suggests that up to 6% of the ssb measured in X- and 22% in alpha-particle-irradiated DNA could have damaged bases associated with them contributing to lesion complexity.

Binding Sites↗