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PubMed1983

Caffeine-mediated release of alpha-radiation-induced G2 arrest increases the yield of chromosome aberrations.

Severe and partly irreversible G2 arrest caused by americium-241 alpha-particles in Chinese hamster V79 cells acted as a competing process to the yield of detectable aberrant mitoses at metaphase. With increasing dose of alpha-radiation an increasing fraction of cells was irreversibly arrested in G2 with the consequence of interphase death before the first post-irradiation mitosis. This irreversible G2 arrest (demonstrated by flow cytofluorometry and mitotic indices) could be overcome by adding caffeine 8 hours after irradiation, the time point of maximum G2 arrest (80-90 per cent of all cells). Within 3.5 hours the number of aberrant mitoses increased by this treatment from 54 to 96 per cent and from 65 to 99.9 per cent for doses of 1.75 and 4.38 Gy of alpha-particles, respectively. The aberration frequency per mitotic cell, scored as chromatid and isochromatid breaks, rings, interchanges and dicentrics increased by a factor of about 3 after releasing G2 arrested cells. The frequency distribution of aberrations per cell revealed that, after 4.38 Gy, 58 per cent of the formerly G2-arrested cells had more than five aberrations per cell compared to only 8 per cent without the interaction of caffeine.

Alpha Particles↗

PubMed2003

Interaction between radiation-induced adaptive response and bystander mutagenesis in mammalian cells.

Two conflicting phenomena, the bystander effect and the adaptive response, are important in determining biological responses at low doses of radiation and have the potential to have an impact on the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we reported previously that nonirradiated cells acquired mutagenesis through direct contact with cells whose nuclei had previously been traversed with either a single or 20 alpha particles each. Here we show that pretreatment of cells with a low dose of X rays 4 h before alpha-particle irradiation significantly decreased this bystander mutagenic response. Furthermore, bystander cells showed an increase in sensitivity after a subsequent challenging dose of X rays. Results from the present study address some of the pressing issues regarding both the actual target size and the radiation dose response and can improve on our current understanding of radiation risk assessment.

Adaptation, Physiological↗

PubMed2004

Microdosimetry of neutron field for boron neutron capture therapy at Kyoto university reactor.

Microdosimetric single event spectrum in a human body simulated by an acrylic phantom has been measured for the clinical BNCT field at the Kyoto University Reactor (KUR). The recoil particles resulting from the initial reaction and subsequent interactions, namely protons, electrons, alpha particles and carbon nuclei are identified in the microdosimetric spectrum. The relative contributions to the neutron dose from proton, alpha particles and carbon are estimated to be about 0.9, 0.07 and 0.3, respectively, four depths between 5 and 41 mm. We estimate that the dose averaged lineal energy, yD decreased with depth from 64 to 46 keV microm(-1). Relative biological effectiveness (RBE) of this neutron field using a response function for the microdosimetric spectrum was estimated to decrease from 3.6 to 2.9 with increasing depth.

Academic Medical Centers↗

PubMed2005

211At radioimmunotherapy of subcutaneous human ovarian cancer xenografts: evaluation of relative biologic effectiveness of an alpha-emitter in vivo.

UNLABELLED: The use of alpha-particle emitters in radioimmunotherapy (RIT) appears to be promising. We previously obtained convincing results in the treatment of microscopic intraperitoneal ovarian cancer in nude mice by using the alpha-emitter 211At. This study was performed to evaluate the relative biological effectiveness (RBE) of 211At compared with that of 60Co gamma-irradiation in an RIT model. Our endpoint was growth inhibition (GI) of subcutaneous xenografts. METHODS: GI after irradiation was studied with subcutaneous xenografts of the human ovarian cancer cell line NIH:OVCAR-3 implanted in nude mice. The animals received an intravenous injection of 211At-labeled monoclonal antibody MX35 F(ab')2 at different levels of radioactivity (0.33, 0.65, and 0.90 MBq). Control mice received unlabeled MX35 F(ab')2 only. To calculate the mean absorbed dose to tumor, a separate biodistribution study established the uptake of 211At in tumors and organs at different times after injection. External irradiation of the tumors was performed with 60Co. Tumor growth was monitored, and the normalized tumor volume (NTV) was calculated for each tumor. GI was defined by dividing the NTV values by the fitted NTV curve obtained from the corresponding control mice. To compare the biologic effects of the 2 radiation qualities, the mean value for GI (from day 8 to day 23) was plotted for each tumor as a function of its corresponding absorbed dose. From exponential fits of these curves, the doses required for a GI of 0.37 (D37) were derived, and the RBE of 211At was calculated. RESULTS: The biodistribution study showed the uptake of the immunoconjugate by the tumor (amount of injected radioactivity per gram) to be 14% after 7 h. At 40 h, the ratio of uptake in tumors to uptake in blood reached a maximum value of 6.2. The administered activities of 211At corresponded to doses absorbed by tumors of 1.35, 2.65, and 3.70 Gy. The value (mean+/-SEM) for D37 was 1.59+/-0.08 Gy. Tumor growth after 60Co external irradiation showed a value for D37 of 7.65+/-1.0 Gy. The corresponding RBE of 211At irradiation was 4.8+/-0.7. CONCLUSION: Using a tumor GI model in nude mice, we were able to derive an RBE of alpha-particle RIT with 211At. The RBE was found to be 4.8+/-0.7.

Alpha Particles↗

PubMed2006

Chromosome breakpoint distribution of damage induced in peripheral blood lymphocytes by densely ionizing radiation.

PURPOSE: To assess the chromosomal breakpoint distribution in human peripheral blood lymphocytes (PBL) after exposure to a low dose of high linear energy transfer (LET) alpha-particles using the technique of multiplex fluorescence in situ hybridization (m-FISH). MATERIALS AND METHODS: Separated PBL were exposed in G0 to 0.5 Gy 238Pu alpha-particles, stimulated to divide and harvested approximately 48 - 50 hours after exposure. Metaphase cells were assayed by m-FISH and chromosome breaks identified. The observed distribution of breaks were then compared with expected distributions of breaks, calculated on the assumption that the distribution of breaks is random with regard to either chromosome volume or chromosome surface area. RESULTS: More breaks than expected were observed on chromosomes 2 and 11, however no particular region of either chromosome was identified as significantly contributing to this over-representation. The identification of hot or cold chromosome regions (pter,p,cen,q,qter) varied depending on whether the data were compared according to chromosome volume or surface area. CONCLUSIONS: A deviation from randomness in chromosome breakpoint distribution was observed, and this was greatest when data were compared according to the relative surface area of each individual chromosome (or region). The identification of breaks by m-FISH (i.e., more efficient observation of interchanges than intrachanges) and importance of territorial boundaries on interchange formation are thought to contribute to these differences. The significance of the observed non-random distribution of breaks on chromosomes 2 and 11 in relation to chromatin organization is unclear.

Alpha Particles↗

PubMed1999

Monte Carlo mixture model of lifetime cancer incidence risk from radiation exposure on shuttle and international space station.

Estimating uncertainty in lifetime cancer risk for human exposure to space radiation is a unique challenge. Conventional risk assessment with low-linear-energy-transfer (LET)-based risk from Japanese atomic bomb survivor studies may be inappropriate for relativistic protons and nuclei in space due to track structure effects. This paper develops a Monte Carlo mixture model (MCMM) for transferring additive, National Institutes of Health multiplicative, and multiplicative excess cancer incidence risks based on Japanese atomic bomb survivor data to determine excess incidence risk for various US astronaut exposure profiles. The MCMM serves as an anchor point for future risk projection methods involving biophysical models of DNA damage from space radiation. Lifetime incidence risks of radiation-induced cancer for the MCMM based on low-LET Japanese data for nonleukemia (all cancers except leukemia) were 2.77 (90% confidence limit, 0.75-11.34) for males exposed to 1 Sv at age 45 and 2.20 (90% confidence limit, 0.59-10.12) for males exposed at age 55. For females, mixture model risks for nonleukemia exposed separately to 1 Sv at ages of 45 and 55 were 2.98 (90% confidence limit, 0.90-11.70) and 2.44 (90% confidence limit, 0.70-10.30), respectively. Risks for high-LET 200 MeV protons (LET=0.45 keV/micrometer), 1 MeV alpha-particles (LET=100 keV/micrometer), and 600 MeV iron particles (LET=180 keV/micrometer) were scored on a per particle basis by determining the particle fluence required for an average of one particle per cell nucleus of area 100 micrometer(2). Lifetime risk per proton was 2.68x10(-2)% (90% confidence limit, 0.79x10(-3)%-0. 514x10(-2)%). For alpha-particles, lifetime risk was 14.2% (90% confidence limit, 2.5%-31.2%). Conversely, lifetime risk per iron particle was 23.7% (90% confidence limit, 4.5%-53.0%). Uncertainty in the DDREF for high-LET particles may be less than that for low-LET radiation because typically there is very little dose-rate dependence. Probability density functions for high-LET radiation quality and dose-rate may be preferable to conventional risk assessment approaches. Nuclear reactions and track structure effects in tissue may not be properly estimated by existing data using in vitro models for estimating RBEs. The method used here is being extended to estimate uncertainty in spacecraft shielding effectiveness in various space radiation environments.

Adult↗

PubMed2002

Choice of alpha-probe operating voltage to suit a wide range of conditions.

Alpha probes, consisting of a ZnS(Ag) scintillator and a photo-multiplier tube, are commonly used throughout the nuclear industry for radiation protection and clearance of materials during decommissioning. The success in achieving these purposes is dependent on a number of factors including the counting efficiency of the probe, the condition of the material being monitored, the speed of monitoring and the distance between the probe and material. The efficiency of the probe is dependent on the operating voltage and is the only factor that is under the control of the calibration facility. As the calibration laboratory may not be aware of the specific environment in which the probe will be used, an operating voltage to suite a wide range of conditions must be chosen. In the past, it has frequently been assumed that it is necessary to set as high an operating voltage as possible in order to maximise the counting efficiency to low-energy alpha particles. However, the response to gamma rays, particularly those having low energies, also increases with operating voltage and will therefore limit the upper operating voltage that can be set. The efficiency of a scintillation-type probe (NE Technology AP2) in measuring contamination levels on a number of typical surfaces using different operating voltages has been investigated. It has been found that the surface characteristics of the material being monitored have far more effect on the results of alpha monitoring than the choice of operating voltage. Thus the calibration laboratory can set the operating voltage below the level at which there is a risk of response to low-energy gamma rays without significantly affecting the overall counting efficiency for low-energy alpha particles.

Alpha Particles↗

PubMed1972

Summary of latent effects in long term survivors of whole body irradiations in primates.

The USAF School of Aerospace Medicine, Radiobiology Division, Brooks Air Force Base, Texas presently is maintaining a colony of over 450 primates in which the whole body has been exposed to various types of space radiation including protons and electrons. The majority of the primates (Macaca mulatta) were exposed during 1965. Types of radiation involved are 2 MeV X-rays, 5 MeV-2.3 GeV protons and 1.6 MeV electrons. Low energy proton dose range up to 3000 rad (50-100 rad min-1) whereas the penetrating energy doses range up to 700 rad (15-100 rad min-1). Primates from a simulated solar flare exposure are also included. In late 1970, a small group of primates exposed to 108 and 85 MeV alpha particles (eye and partial body only) were added to the colony. Data are available in the following areas: (i) chronic skin changes; (ii) testicular atrophy; (iii) cataractogenesis; (iv) hematological and serum biochemical analysis; (v) incidence of tumors; (vi) causes of death; (vii) body weight variations; and (viii) summary of alpha particle experiences.

Alpha Particles↗

PubMedDate not supplied

[Fast repair in diploid yeast cells after combined exposure to ionizing radiation with different LET].

Fast repair in diploid yeast cells Saccharomyces cerevisiae XS800 exposed to the combined irradiation (alpha-particles + high-velocity electrons) was studied. It has been shown that fast repair was significantly more effective after combined irradiation with high doses than after exposure to high-velocity electrons or alpha-particles alone. The regions of radioresistance in the cell survival curves after combined irradiation can be explained by fast post-irradiation repair.

Alpha Particles↗

PubMed1990

The DNA content of some mammalian cells measured by flow cytometry and its influence on radiation sensitivity.

The DNA content of nine mammalian cell lines was determined by flow cytometry. Using radiobiological data from this and other laboratories a correlation between DNA mass and 1/D0 for X-rays, alpha-particles, and heavy ions could be established when the quantities were plotted on a log-log scale. The slopes of the regression lines amounted to 0.65 (X-rays), 0.64 (alpha-particles) and 0.74 (heavy ions). A similar correlation was found between DNA content and mean inactivation dose. The rather uniform slopes close to 2/3 suggest that radiosensitivity may depend on the surface area of the sensitive target, (cell nucleus) indicating a possible non-uniform distribution of radiosensitive sites within the nucleus.

Alpha Particles↗

PubMed2006

Fast Monte Carlo simulation of DNA damage formed by electrons and light ions.

The passage of ionizing radiation through living organisms initiates physical and chemical processes that create clusters of damaged nucleotides within one or two turns of the DNA. These clusters are widely considered an important initiating event for the induction of other biological endpoints, including cell killing and neoplastic transformation. Monte Carlo simulations of the DNA damage formation process are a useful adjunct to experiments because they provide additional information about the spatial configuration of damage within a cluster. In this paper, the fast Monte Carlo damage simulation (MCDS) algorithm is re-parameterized so that yields of double-strand breaks, single-strand breaks and sites of multiple base damage can be simulated for electrons, protons and alpha particles with kinetic energies on the order of GeV. The MCDS algorithm provides a useful, quasi-phenomenological scheme to interpolate damage yields from computationally expensive, but more detailed, track-structure simulations. The predicted characteristics of various classes of damage produced by electrons, protons and alpha particles, such as average number of lesions per DNA damage cluster and cluster length in base pairs, are presented. A study examining the effects on damage complexity of an extrinsic free radical scavenger, dimethyl sulfoxide, is also presented. The reported studies provide new information that will aid efforts to characterize the relative biological effectiveness of high-energy protons and other light ions, which are sometimes used in particle therapy for the treatment of cancer.

Algorithms↗

PubMed2006

In vitro screening for synergism of high-linear energy transfer 213Bi-radiotherapy with other therapeutic agents for the treatment of B-cell chronic lymphocytic leukemia.

BACKGROUND: External beam radiotherapy and beta-radioimmunotherapy (RIT) are effective treatments for lymphoid malignancies. The development of RIT with alpha-emitters is attractive, owing to the high (LET) nature and short path length of alpha particles allowing for higher tumor cell kill and lower toxicity to healthy tissues. OBJECTIVES: The aim of this study was to assess the response of B-Cell chronic lymphocytic leukemia (B-CLL) cells in vitro after treatment with chemotherapy (cisplatin, fludarabine, doxorubicin, or vincristine) or other pharmaceuticals (colchicine, simvastatin, or cyclosporin A) in combination with (60)Co-gamma or (213)Bi-alpha-irradiation. METHODS: (213)Bi was eluted from a (225)Ac generator. Apoptosis was scored by flow cytometric analysis of the cells stained with Annexin-V and 7 amino actinomycin D. Metabolic activity was assessed by a MTT assay. RESULTS: The response induced by alpha- irradiation is systematically higher than the response induced by gamma-irradiation. The combination of drug treatment with alpha-irradiation induced a systematic, higher response, compared to treatment with drugs alone, even for the highest concentrations used. For all the drugs used in this study, synergism or additivity was demonstrated for the combination of drugs and radiotherapy with a stronger effect for alpha-particles. CONCLUSIONS: The results of this in vitro study highlight a potential benefit of alpha-irradiation in combination with the drugs considered in this study.

Alpha Particles↗

PubMed2002

In vitro cell irradiation systems based on 210Po alpha source: construction and characterisation.

One way of studying the risk to human health of low-level radiation exposure is to make biological experiments on living cell cultures. Two 210Po alpha-particle emitting devices, with 0.5 and 100 MBq activity, were designed and constructed to perform such experiments irradiating monolayers of cells. Estimates of dose rate at the cell surface were obtained from measurements by a PIPS alpha-particle spectrometer and from calculations by the SRIM 2000, Monte Carlo charged particle transport code. Particle fluence area distributions were measured by solid state nuclear track detectors. The design and dosimetric characterisation of the devices are discussed.

Alpha Particles↗

PubMedDate not supplied

[Comparative study of RBE of densely ionizing radiation for various types of cell death in yeast].

A comparative study of the relative biological effectiveness (RBE) of alpha-particles 249Pu for reproductive and interphase forms of killing of haploid and diploid yeast cells of wild-type and their radiosensitive mutants has been carried out. The correlation between the RBE of alpha-particles and cell repair capacity was confirmed for reproductive death: it was the highest for diploid cells, smaller for haploid cells and the smallest for their radiosensitive mutants. To achieve the interphase cell killing much higher irradiation doses were used after which cells were incapable of liquid-holding recovery during the storing of exposed cells in non-nutrient media at 30 degrees C. The RBE values for this form of killing were significantly lower in comparison with reproductive death. These data are an additional argument supporting the point of view that the RBE of densely ionizing radiation is determined not merely by physical processes of energy absorption as it is traditionally believed but also by ability of cells to recover from DNA damages inflicted by ionizing radiation.

Alpha Particles↗

PubMed1986

On the reported deviations of the stopping cross section of water vapor from the Bragg additivity rule.

A comparison of recent experimental values of the stopping cross section epsilon of water molecules in the gaseous phase for alpha particles of various kinetic energies E is made with the corresponding Bragg additivity rule values of H2O based on various experimental values of epsilon of gaseous H2 and O2. Some of the Bragg rule values of epsilon of H2O for alpha particles show remarkable (approximately less than 1%) agreement with experimental values even at low E thus suggesting that experimental error may be the main cause of the reported deviations over the last approximately 50 y.

Alpha Particles↗

PubMed1998

Radiation-induced genomic instability in haemopoietic cells.

PURPOSE: To review studies of radiation-induced genomic instability in haemopoietic cells. MAJOR FINDINGS: Studies have demonstrated a high frequency of non-clonal, cytogenetic abnormalities in the clonal descendants of alpha-particle-irradiated (approximately one track per cell) primary murine and human haemopoietic stem cells in vitro. The induction of this phenomenon has a strong dependence on the genetic characteristics of the cells and is transmissible in vivo following transplantation of alpha-irradiated mouse bone marrow. In clonogenic cell cultures of alpha-irradiated haemopoietic cells, there is also an increased incidence of hprt mutations and an increased incidence of apoptosis. These effects may be regarded as the consequences of a destabilization of the genome collectively termed radiation-induced genomic instability. Instability is induced at very high frequencies suggesting that epigenetic changes may be a common underlying mechanism. Consistent with this suggestion is the finding of an enhanced and persisting oxy-radical activity in the descendants of irradiated stem cells, which is consistent with oxidative stress being an important feature of the mechanism(s) underlying the persistence of instability in haemopoietic cells. Recent studies have revealed that more clonogenic cells than are actually traversed by an alpha-particle are able to express the instability phenotype. These data are consistent with unexpected interactions between irradiated and non-irradiated cells but the mechanism of initiation of instability is not understood.

Alpha Particles↗

PubMed1984

Recovery from transcription inhibition in irradiated yeast cells.

Repair process operating on radiation damaged DNA may be investigated by studying its functional integrity, e.g. its ability to serve as template for transcription. We measured the synthesis of ribosomal RNA and of the inducible enzyme arginase in yeast cells and followed their recovery after X-ray, alpha-particle and heavy ion exposure. Transcription inhibiting lesions formed upon X-irradiation in yeast cells are repaired during post-exposure incubation ("liquid-holding"). The inactivation curves are strictly exponential immediately after irradiation. After the "liquid holding" treatment the inactivation curves are still exponential but with a progressive decrease of the slopes as a function of incubation time. This indicates that a constant fraction of the lesions is repaired per time interval. But even after long incubation times (24 h) there is still a sizeable unrepaired fraction. Comparing different yeast strains and different irradiation temperatures recovery can also be demonstrated in cells exposed to alpha-particles. In addition, recovery is detected by the arginase assay after irradiation of yeast with very heavy charged particles, e.g. titanium ions.

Alpha Particles↗

PubMed2001

Status and problems of fusion reactor development.

Thermonuclear fusion of deuterium and tritium constitutes an enormous potential for a safe, environmentally compatible and sustainable energy supply. The fuel source is practically inexhaustible. Further, the safety prospects of a fusion reactor are quite favourable due to the inherently self-limiting fusion process, the limited radiologic toxicity and the passive cooling property. Among a small number of approaches, the concept of toroidal magnetic confinement of fusion plasmas has achieved most impressive scientific and technical progress towards energy release by thermonuclear burn of deuterium-tritium fuels. The status of thermonuclear fusion research activity world-wide is reviewed and present solutions to the complicated physical and technological problems are presented. These problems comprise plasma heating, confinement and exhaust of energy and particles, plasma stability, alpha particle heating, fusion reactor materials, reactor safety and environmental compatibility. The results and the high scientific level of this international research activity provide a sound basis for the realisation of the International Thermonuclear Experimental Reactor (ITER), whose goal is to demonstrate the scientific and technological feasibility of a fusion energy source for peaceful purposes.

Deuterium↗