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PubMed1995

Oncogenic transformation of C3H 10T1/2 cells exposed to alpha particles: sensitivity through the cell cycle.

Oncogenic transformation of synchronized C3H 10T1/2 cells was determined after exposure to 4.3 MeV alpha particles (LET = 101 keV/microns). Two synchronization techniques were tested using basic and modified protocols: one based on the release of cells from contact inhibition and the second on the mitotic shake-off method. Progression of cells through the cycle was followed as a function of time by flow cytometric analysis, DNA labeling for passage through S phase, the growth curve for the cell number and mitotic index measurements. The conclusion is that, although the release of cells from confluence provides higher yields of synchronized cells, mitotic shake-off proved to be the best way of collecting a synchronized population of minimally perturbed cells. Cells synchronized by mitotic shake-off were irradiated with 0.30 Gy in the interval between 2 and 10 h corresponding to G1 and early S phases. For comparison asynchronous populations were irradiated in parallel. Oncogenic transformation frequency, corrected for background, in mid-G1 phase was (18 +/- 4) x 10(-5) (average values of frequencies at 4 and 6 h) compared with the value of (8 +/- 4) x 10(-5) for the asynchronous population. While these data are suggestive of a trend toward a slightly increased sensitivity in mid-G1 phase, it is not statistically significant. The surviving fraction is constant in G1 phase.

3T3 Cells↗
PubMed1999

Comments on ICRU report no. 49: stopping powers and ranges for protons and alpha particles.

The International Commission on Radiation Units and Measurements (ICRU) published Report No. 49, Stopping Powers and Ranges for Protons and Alpha Particles, in 1993. Since the report shows only limited comparisons to experimental data, this Commentary discusses limits on the accuracy of its tables. Some of the stopping tabulations appear to have unusual variations for high energies (>1 MeV/nucleon) of the order of 2-4%, while the lower energies have possible errors of 10-20% for those targets which were not fitted with new data.

Alpha Particles↗
PubMedDate not supplied

Fast adaptive alpha-particle spectrum fitting algorithm based on genetically estimated initial parameters.

This work presents a high performance procedure for the unfolding of alpha particle spectra based on genetically estimated initial parameters. The process starts with the search for a globally optimized set of fitting parameters from a population of randomly generated solutions. The solution found with the genetic algorithm is then transferred to a Levenberg-Marquardt procedure in order to calculate the covariance matrix for the fit. The proposed method provides the set of final parameters and their associated standard deviation. Several fitted spectra demonstrate the effectiveness of the proposed method in searching for and finding initial conditions in a fast and automated process.

Algorithms↗
PubMed1997

212Bi-DOTMP: an alpha particle emitting bone-seeking agent for targeted radiotherapy.

The synthesis and in vivo stability of the bone-seeking alpha-particle emitting compounds 212Bi-DOTMP and 212Pb/212Bi-DOTMP are described. 212Bi-DOTMP, injected i.v. into Balb/c mice, showed prominent bone localization and a rapid clearance from blood and other organs. Femur/blood ratios increased from 13 at 15 min up to 490 at 2.0 h postinjection. Enhanced uptake of 212Bi-DOTMP was demonstrated in regions with high bone turnover. A comparison between 212Bi-DOTMP and [153Sm]Sm-EDTMP showed essentially no differences in biodistribution. 212Pb/212Bi-DOTMP followed a similar biodistribution, except for slightly elevated levels of 212Bi in the kidneys. The present study has shown 212Bi-DOTMP to be an in vivo stable bone-seeking radiopharmaceutical with promising biological properties for the treatment of sclerotic metastases and osteoblastic osteosarcoma.

Alpha Particles↗
PubMed1997

Cytotoxicity of alpha-particle-emitting 5-[211At]astato-2'-deoxyuridine in human cancer cells.

This study was performed to determine the cytotoxicity of alpha-particle-emitting 5-[211At]astato-2-deoxyuridine (i.e. [211At]AUdR) for monolayers of D-247 MG human glioma cells and SK-MEL-28 human melanoma cells. Cells in exponential growth were exposed to varying activity concentrations of [211At]AUdR and for comparison [211At]astatide and the Auger electron-emitting analogue, 5-[125I]iodo-2'-deoxyuridine (i.e. [125I]IUdR). Cell uptake, DNA binding and clonogenic survival as a function of activity concentration in the medium were determined following 2 and 20-h incubations. None of the survival curves had detectable shoulders, an observation consistent with high-LET effects. The A37 (initial activity concentration yielding 37% cell survival) were significantly lower for both cell lines following 20-h exposure of [211At]AUdR than [211At]astatide. After correcting for effects from non-cell-associated activity in the medium, the specific cytotoxicity of cell-associated and DNA-bound [211At]AUdR was estimated. In the 20-h incubation experiments, the A37 for DNA-associated [211At]AUdR corresponded to about one 211At atom bound per cell for both cell lines. Unlike [211At]AUdR, there was a biphasic survival response to [125I]IUdR, consistent with the lower fractional uptake of [125I]IUdR at higher activity concentrations. These studies suggest that [211At]AUdR warrants further evaluation as an endoradiotherapeutic agent for the treatment of rapidly proliferating cancers.

Alpha Particles↗
PubMed1998

Intratumour injection of immunoglobulins labelled with the alpha-particle emitter 211At: analyses of tumour retention, microdistribution and growth delay.

To determine the effects of 211At-labelled antibodies in solid tumour tissue, nude mice carrying OHS human osteosarcoma xenografts received intratumour injections at dosages of 1, 2 or 4 MBq (-1) tumour. The radioisotope was conjugated to either the osteosarcoma-specific monoclonal antibody TP-3 or the non-specific polyclonal antibody hlgGkappa. Tumour retention of injected radioimmunoconjugate (RIC), measured as the percentage of injected activity dosage per gram, was significantly higher for the [211At]TP-3 (203 +/- 93 at 24.1 h post injection) compared with the [211At]hlgGkappa (57 +/- 22 at 23.2 h post injection). The radioactive count rates in body (measured at neck and abdomen) were significantly lower with the TP-3 than with the hlgGkappa. Microautoradiography of the tumour radionuclide distribution was different for the two RICs, i.e. the [211At]TP-3 was to a larger extent concentrated near the injection site, whereas the [211At]hlgGkappa was more evenly distributed all over the tumour. The tumour growth was significantly delayed as a function of the injected activity dosage but without significant difference between the specific and the non-specific RIC. According to this study, it is possible to deliver highly selective radiation doses to solid tumours using intratumour injection of alpha-particle-emitting RICs. Improved tumour retention caused by antigen binding indicates that reduced normal tissue exposure can be obtained with antigen-specific antibodies. The heterogeneous tumour dose distribution observed is, however, a major impediment to the use of alpha-particle emitters against solid tumours.

Animals↗
PubMed2000

Factors underlying the cell growth-related bystander responses to alpha particles.

Increases in cell proliferation are widely viewed as being of importance in carcinogenesis. We report that exposure of normal human lung fibroblasts to a low dose of alpha particles like those emitted by radon/radon progeny stimulates their proliferation in vitro, and this response also occurs when unirradiated cells are treated with supernatants from alpha-irradiated cells. We attribute the promitogenic response to superoxide dismutase- and catalase-inhibitable a particle-induced increases in the concentrations of transforming growth factor beta1 (TGF-beta1) in cell supernatants. TGF-beta1 at concentrations commensurate with those in the supernatants capably induces increases in intracellular reactive oxygen species (ROS) in unirradiated cells. Furthermore, the addition of supernatants from alpha-irradiated cells to unirradiated cells decreases cellular levels of TP53 and CDKN1A and increases CDC2 and proliferating cell nuclear antigen in the latter. Like the increased intracellular ROS bystander effect, this "decreased TP53/CDKN1A response" can be mimicked in otherwise untreated cells by the addition of low concentrations of TGF-beta1. Our results indicate that alpha particle-associated increases in cell growth correlate with intracellular increases in ROS along with decreases in TP53 and CDKN1A, and that these cellular responses are mechanistically coupled. As well, the proliferating cell nuclear antigen and CDC2 increases that occur along with the decreased TP53/CDKN1A bystander effect also would expectedly favor enhanced cell growth. Such processes may account for cell hyperplastic responses in the conducting airways of the lower respiratory track that occur after inhalation exposure to radon/ radon progeny, as well as, perhaps, other ROS-associated environmental stresses.

Alpha Particles↗
PubMed2000

Exposure of human osteosarcoma and bone marrow cells to tumour-targeted alpha-particles and gamma-irradiation: analysis of cell survival and microdosimetry.

PURPOSE: This study was designed to compare the cytotoxic effects of an alpha-emitting radioimmunoconjugate, which binds to osteosarcoma but not to bone marrow cells, with those of external gamma-irradiation. MATERIALS AND METHODS: The human osteosarcoma cell line, OHS-s1, and mononuclear cells from bone marrow (BM) harvested from healthy donors, were used for these experiments. Cells in suspension were added to various activity concentrations of the anti-osteosarcoma monoclonal antibody TP-3 radiolabelled with 211At. Following incubation for 1 h, unbound radioactivity was washed off and cell survival was determined from clonogenic assays. Microdosimetry was calculated based on binding and retention kinetics of 211At to the cells, as well as cellular and nuclear diameters. For comparison, cell suspensions were irradiated with a single dose of 60Co gamma-rays. RESULTS: 211At-labelled TP-3 showed heterogeneous binding to OHS-s1 cells, with a considerable variation among experiments. About 78% of the initially bound 211At decayed while associated with the OHS-s1 cells. D0 values estimated by microdosimetry were 0.33 (0.22-0.48, range) Gy and 1.18 (0.89-1.89) Gy for OHS-s1 and BM cells, respectively, whereas D0 values after external beam irradiation were 0.86+/-0.07Gy and 1.71+/-0.22Gy. The relative biological effectiveness (RBE) of 211At-labelled TP-3 at 37% survival was 3.43 for OHS-s1 and 1.55 for BM. CONCLUSIONS: High-LET targeted alpha-particle exposure killed osteosarcoma cells more effectively than bone marrow cells, although heterogeneous antigen expression among these tumour cells limited the magnitude of this effect.

Alpha Particles↗
PubMed1996

Evidence for an effect of exposure to low levels of alpha particle irradiation in larval cells of Drosophila as measured in the wing-spot test.

Larvae of Drosophila were exposed to a range of concentrations of alpha particles from 3 to 318 mRad, and genetic effects measured in the wing-spot test. The results were positive, and evidence of a linear relationship between exposure and response observed. The induction of chromosome breakage is suggested by the significantly higher frequency of twin spots in the treated series compared with controls.

Alpha Particles↗
PubMed1979

Determination of the stopping cross-sections of N2, H2, CH4, C4H10 and C3H6 using alpha particles in the range 1 . 3--4 . 2 MeV.

The stopping cross-sections of N2, H2, CH4, C4H10 and C3H6 have been measured using natural alpha particles from a 238Pu source, with facilities to vary the energy in the range 1.3--4.2 MeV. The work is the extension of measurements made earlier, using C2H4 as the absorber, which showed discrepancies in comparison with results of other authors. The comparison is continued with the results presented here and brief comments made on the degree of agreement obtained.

Alkanes↗
PubMed2000

Metastability of Si1-yCy epilayers under 2 MeV alpha-particle irradiation

In this work we present some recent results concerning the alpha-particles irradiation of Si1-yCy alloy epitaxially grown on silicon. The study of the damage process is interesting because of the extensive use of backscattering technique as a tool of characterisation of this kind of materials and because of the possibility of adding information about the transformations that this metastable material undergoes. We point out that the irradiation damage process causes a change in the material structure different from that due to the thermal treatments. The irradiation damage occurs at a rate much higher than in Si, however it involves only a silicon atom fraction that appears to be proportional to the substitutional carbon content.

Journal Article↗
PubMedDate not supplied

[Modification of the damaging effect of alpha-particles on Escherichia coli K-12 by low-intensity laser irradiation].

A study was made of the combined effect of laser (helium-neon laser, lambda = 633 nm) and alpha-radiation on survival of Escherichia coli K-12 cells of different genotypes. Pre- and post-irradiation exposures to laser-radiation diminished the damaging effect of alpha-particles. In the latter case, modification of survival was more pronounced.

Alpha Particles↗
PubMed1978

Frequency of alpha-particles from 239PuO2 in lung cells.

NCRP-Report 49 deals with the effect of 239PuO2-particles in the lung. A basic aspect in the considerations is the frequency of cells traversed by one or by more alpha-particles. The present article contains the explicit derivation of the formulae underlying the data in the NCRP-report.

Alpha Particles↗
PubMed2002

The formation of ionisation clusters by alpha particles in 'nanometric' volumes of nitrogen: experiment and calculation.

Probability distributions of the size of ion clusters created in 'nanometric' cylindrical volumes of nitrogen by single 4.6 MeV alpha particles were measured and compared with those calculated by Monte Carlo simulation. The diameter of the sensitive volume had a mass per area of between 0.015 and 1.3 micrograms.cm-2 which, for a material at unit density, corresponds to a diameter of between 0.15 nm and 13 nm. These nanometre sizes were simulated experimentally in a device called Jet Counter. The measured or calculated cluster size probabilities confirmed that the formation of ionisation clusters along a 'nanometre' track can be characterised by Poisson's distribution only for very small targets. The present ionisation cluster probabilities produced in 'nanometric' volumes, 2 to 10 nm in diameter, are the first ever determined experimentally and confirmed by Monte Carlo simulation.

Alpha Particles↗
PubMed1983

alpha-Particle track autoradiography for localization of a 211At-astatinated drug.

A potential endoradiotherapeutic drug, 6-211At-astato-2-methyl-1,4-naphthoquinol bis (diphosphate salt), incorporating the alpha-emitting radio-halogen astatine-211 of half-life 7.2 h, is shown to be valuable for localization studies by means of alpha-particle track autoradiography in malignant and normal cells and tissues in the mouse with transplanted adenocarcinoma of the rectum.

Adenocarcinoma↗
PubMed1996

Estimation of single-strand breaks induced in the dried film of DNA by high energy alpha particle from a cyclotron.

DNA extracted and purified from Vibrio cholerae OGAWA 154 cells and prepared in the form of a dry thin film was exposed in air to a beam of alpha particles obtained from a Variable Energy Cyclotron. The number of single-strand breaks per DNA unit exhibited a linear dose-effect relationship indicating the occurrence of single-hit kinetics. The efficiency and yield of alpha-induced single-strand breaks were approximately 72 eV/break and 1.39 respectively.

Alpha Particles↗