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PubMed1982

The microdosimetry of lymphocytes irradiated by alpha-particles.

Although the concept of absorbed dose is commonly used in radiation biology as a parameter for comparing the toxic effect of different levels of radiation on a system, there are situations where the absorbed dose by itself is inadequate, and additional dose distribution information is required to explain the observed biological effects. A good example is the irradiation of cells by alpha-particles. This paper reports the use of internal microdosimetry techniques to reinvestigate the dosimetry to two very similar experiments with apparently contradictory dose-response results. Yields of dicentric chromosome aberrations induced in human blood lymphocytes following in vitro exposure to dissolved americium or plutonium at two separate laboratories produced linear dose-response functions, but the slopes of the best-fit straight lines differed by a factor of 12. Our microdosimetric analysis showed the results of one experiment to be inconsistent with a uniform distribution of activity. It also showed that the difference in slope could be attributed to differences in particulate size and spatial distribution as a result of dissimilarities in procedures used for preparing the actinide solutions.

Alpha Particles↗
PubMed2003

New interpretation of alpha-particle-driven instabilities in deuterium-tritium experiments on the Tokamak Fusion Test Reactor.

The original description of alpha particle driven instabilities in the Tokamak Fusion Test Reactor in terms of toroidal Alfvén eigenmodes (TAEs) remained inconsistent with three fundamental characteristics of the observations: (i) the variation of the mode frequency with toroidal mode number, (ii) the chirping of the mode frequency for a given toroidal mode number, and (iii) the antiballooning density perturbation of the modes. It is now shown that these characteristics can be explained by observing that cylindrical-like modes can exist in the weak magnetic shear region of the plasma that then make a transition to TAEs as the central safety factor decreases in time.

Journal Article↗
PubMed2002

Bone tumorigenesis induced by alpha-particle radiation: mapping of genetic loci influencing predisposition in mice.

The present study was carried out to determine the extent to which genetic factors modify the incidence of radiation-induced bone tumorigenesis in mice, and to map putative susceptibility genes. We conducted a genome-wide linkage analysis in a cohort of 47 interstrain backcrossed mice. After the mice were injected with the bone-seeking alpha-particle-emitting radionuclide (227)Th, 21 of the mice developed osteosarcomas. Two loci, one on chromosome 7 close to D7Mit145 and a second on chromosome 14 (D14Mit125), exhibited suggestive linkage to osteosarcoma predisposition, with LOD scores of 1.37 and 1.05, respectively. The LOD score increased considerably when interaction between these two loci was taken into account (LOD = 3.48). Nine of 12 mice inheriting a susceptibility allele at both loci developed osteosarcomas after (227)Th injection, compared to only four osteosarcomas in 18 animals that did not inherit either of the susceptibility alleles. Variance component analysis revealed that these genetic factors determine approximately one-fifth of the total incidence of osteosarcomas. This study demonstrates the presence of a genetic component that modulates predisposition to radiation-induced osteosarcoma.

Aging↗
PubMed2002

On the equivalence of propane-based tissue-equivalent gas and liquid water with respect to the ionisation-yield formation by electrons and alpha-particles.

One encouraging way, at present, to put the investigation of ionisation-yield formation in sub-cellular structures or, at least, in nanometric volumes of liquid water on an experimental basis is the use of highly sophisticated counters filled with gases at low operating pressure to simulate target volumes a few nm in diameter at unit density. To check the validity of such measurements, the ionisation-yield formation by electrons and alpha particles in liquid water was simulated using the Monte Carlo method and compared with that produced in propane-based tissue-equivalent gas (composition by volume: 55% C3H8, 39.6% CO2, 5.4% N2). After a short summary of the most important physical aspects of ionisation cluster formation, new results are presented and discussed from the point of view of radiation physics and radiation biology.

Alpha Particles↗
PubMed1981

Stopping cross-sections of liquid water and water vapour for alpha particles within the energy region 0.3 to 5.5 MeV.

Phase effects in the stopping power of heavy charged particles are important in dosimetry and, in particular, in cavity chamber theory and in the design and operation of homogeneous gas-filled ionisation chambers for neutron dosimetry. A single apparatus has been designed to allow measurement of stopping cross-sections of materials in liquid and vapour phase for alpha particles. Experimental stopping powers of water vapour are presented for energies from 0.3 to about 5.5 MeV and of liquid-phase water from 1.75 to 4.75 MeV. The molecular stopping cross-sections of the vapour tend to be greater than those for the liquid. The differences between the stopping powers for the two states of H2O indicate phase effects of no more than about 4% in the energy region of comparison (down to 1.75 MeV), with an increasing trend towards lower energies. Major fluctuations in stopping power ratio are not observed in this energy region.

Alpha Particles↗
PubMed2002

Vascular targeted endoradiotherapy of tumors using alpha-particle-emitting compounds: theoretical analysis.

PURPOSE: To establish the theoretical framework and study the feasibility of (211)At-labeled anti-tenascin chimeric 81C6 monoclonal antibody (mAb) as anti-vascular endoradiotherapy for the treatment of glioblastoma multiforme (GBM) tumors. METHODS AND MATERIALS: The morphology of blood vessels from histologic images was analyzed and used along with reaction-diffusion equations to assess the activity concentration of (211)At-labeled chimeric 81C6 mAb in GBM tumor and normal-brain tissue. Alpha particle microdosimetry was then used to assess the survival probability and average absorbed dose for tumor and normal tissue endothelial cells (ECs) per unit vascular cumulated activity concentration q(source) (MBq-s g(-1)). In turn, these survival probabilities were used to assess the probability of failure Phi for a single vessel. Furthermore, using the vessel density, the specific tumor control probability per unit mass of tumor tissue (tcp) and the specific normal-tissue complication probability per unit mass of normal-brain tissue (ntcp) were estimated. The specific tumor control probability, tcp, was used to assess the overall tumor control probability (TCP) as a function of tumor mass. RESULTS: The levels of (211)At-labeled ch81C6 mAb cumulated activity concentration in GBM tumor tissue were approximately five times higher than that in normal-brain tissue. Thus, the average absorbed dose to tumor ECs was higher than that of normal tissue ECs, and the survival probability for GBM ECs was lower than for normal-brain tissue ECs. Consequently, the resulting vessel-failure probability, Phi, for GBM tumor and for normal-brain tissue differ considerably, yielding a q(source) range between 10(3) and 10(4) MBq-s g(-1). CONCLUSIONS: This theoretical analysis demonstrated that (211)At-labeled chimeric 81C6 is an effective anti-vascular therapy for the treatment of GBM tumors, yielding a tcp higher than 0.999 for vascular cumulated activity concentrations q(source) higher than 1 x 10(4) MBq-s g(-1), while yielding a low probability for normal-brain tissue damage.

Alpha Particles↗
PubMed1994

Similarities between human ataxia fibroblasts and murine SCID cells: high sensitivity to gamma rays and high frequency of methotrexate-induced DHFR gene amplification, but normal radiosensitivity to densely ionizing alpha particles.

Two gamma-ray hypersensitive cell lines, human ataxia telangiectasia (AT) and murine severe combined immune deficiency (SCID) cells, proved to be very competent in amplifying their dihydrofolate reductase (DHFR) gene under methotrexate selection stress. Over a period of months, methotrexate-resistant clones were obtained which were able to grow in progressively increasing methotrexate concentrations up to 1 mM. By then methotrexate-resistant AT and SCID cells had amplified their DHFR gene 6- and 30-fold, respectively, and showed very high DHFR mRNA expression. In contrast, related cells with normal radiosensitivity (human GM637 and mouse BALB/c fibroblasts) did not show DHFR gene amplification under comparable conditions. This correlation of the capacity of DHFR gene amplification and gamma-ray hypersensitivity in AT and SCID cells suggests that gene amplification may have a mechanism(s) in common with those involved in repair of gamma-radiation-induced damage. No difference in cell killing could be observed following exposure to densely ionizing alpha particles: AT and SCID cells exhibited comparable survival rates to GM637 and BALB/c cells, respectively.

Alpha Particles↗
PubMed1996

Microdosimetry of haemopoietic stem cells irradiated by alpha particles from the short-lived products of 222Rn decays in fat cells and haemopoietic tissue.

The Monte Carlo method is used to model fat cells and the nuclei of stem cells in haemopoietic tissue where 222Rn is dissolved in different amounts in the fat and tissue. Calculations are performed for fat cells of diameters 50 and 100 microns and for stem cell nuclei of 8 and 16 microns diameters for various fractions of fat filling the volume. Average doses (and their distributions) to stem cell nuclei from single passages of alpha particles are presented. In addition to dose, the relationship between LET and dose is obtained, illustrating the importance of 'stoppers' in the calculations. The annual average dose equivalent for a concentration of 1 Bq/m3 in air agrees well with other authors at 12 mu Sv/year. The method also allows the calculation of the fraction of stem cell nuclei hit annually. Here for 1 Bq/m3, stem cell nuclei of diameter 8 microns and 100% fat filing 15 x 10(-7) of the stem cell nuclei are hit.

Adipocytes↗
PubMed2002

Double strand break rejoining after irradiation of human fibroblasts with X rays or alpha particles: PFGE studies and numerical models.

When a charged-particle track intercepts the chromatin fibre in DNA of mammalian cells, clustered damage is induced depending on the DNA conformation, local environment and track structure. Intra-track correlated DNA damage may have a higher probability of being mis-repaired or left un-repaired. Fragment size-distributions of DNA double strand breaks (DSBs) induced in primary human fibroblasts by 240 kVp X rays and 238Pu alpha particles (110 keV.micron-1) were resolved using pulsed-field gel electrophoresis (PFGE). By monitoring DSB rejoining kinetics and changes in the fragment size distribution with repair time, the relevance of spatial association of DSBs in determining rejoining kinetics was investigated. Rejoining kinetics appeared bi-phasic and independent of the size of the DNA fragments for both radiation qualities, with high LET radiation-induced DSBs repairing more slowly. Results suggest that local complexity of individual DSBs, rather than spatial association with other breaks is more significant in the determination of rejoining kinetics.

Alpha Particles↗
PubMed1995

The biological effectiveness of radon-progeny alpha particles. III. Quality factors.

Domestic radon risk estimates are typically based either on data for uranium miners or on data derived from A-bomb survivors; comparison of domestic radon risk estimates derived from these two disparate sources represents an important test of their reliability. There is currently a significant discrepancy of about a factor of three between domestic radon risk estimates generated with these two independent methods. To base such risk estimates on the data for A-bomb survivors, who were exposed mainly to low-LET radiation, requires a quality factor for alpha particles from random progeny; the final risk estimate is then directly proportional to this quality factor. We have used the most extensive quantitative in vitro data set currently available at high LET for an oncogenic end point, to make the best estimate we can that could be used as a basis for a quality factor. Our best estimates of values appropriate for the quality factor for radom progeny are significantly lower than those currently used (20-25) in estimating lung cancer mortality due to randon. Specifically, our best estimate for home dwellers is around 10. In addition, because of the different geometry in the bronchial epithelia of nonsmokers compared to smokers, our best estimate of an appropriate quality factor for home dwellers is about 18% greater than that for miners; thus our best estimate of the "effective K factor" to convert to effective dose/WLM in home dwellers from effective dose/WLM in miners would be increased by this factor. Based on a quality factor of approximately 10, the dosimetrically based estimate of radon-induced mortality would be approximately 35,000 per year in the U.S. rather than the value of approximately 70,000 obtained using a quality factor of 20. The value of 35,000, while larger than the values based on data for miners (approximately 20,000), is much smaller than previous estimates of approximately 70,000 based on dosimetric methods; thus risk estimates based on the two approaches, dosimetric and epidemiological, may be partially reconciled. Finally, a quality factor of 10 would reduce the proportion of the collective effective dose caused by radon progeny from the currently accepted value of 55% down to about 38%.

Alpha Particles↗
PubMed2005

Analysis of secondary electron emission spectra of equal-LET protons and alpha particles for purposes of radiation quality and spaceflight hazard assessment.

Amongst the great variety of heavy particles present in the galactic and solar cosmic ray spectra, hydrogen and helium nuclei are significantly more abundant than all other heavier ions and, as such, represent a major radiation hazard to humans in space. Experimental data have suggested that differences in relative biological effectiveness (RBE) exist between the two species at the same value of linear energy transfer (LET). This has consequences for heavily ionising radiation protection procedures, which currently still assume a simple dependence of radiation quality on LET. By analysing the secondary electron (delta-ray) emission spectra of protons and alpha particles, in terms of the spatial characteristics of energy deposition in cellular targets and the likelihood of complex lesion formation, a numerical quantity representing biological effectiveness is generated. When expressed relative to a reference radiation, this quantity is found to differ for protons and a particles of the same LET, demonstrating not only the ion-specific nature of RBE but also the inadequacy of specifying radiation quality as a function of LET only. Such a method for numerically assessing radiation quality may have implications for procedures for heavy ion protection in space at low doses and for understanding the initial mechanisms of radiation action.

Alpha Particles↗
PubMed2002

The relationship between internally deposited alpha-particle radiation and subsite-specific liver cancer and liver cirrhosis: an analysis of published data.

Chronic exposure to high LET radiation has been shown to cause liver cancer in humans based on studies of patients who received Thorotrast, a colloidal suspension of thorium dioxide formerly used as a radiological contrast agent, and on studies of Russian nuclear weapons workers exposed to internally ingested plutonium. Risk estimates for these exposures and specific subtypes of liver cancer have not been previously reported. Combining published data with tumor registry data pertinent to the Thorotrast cohorts in Germany, Denmark, Portugal, and Japan and to Russian workers, we generally found significantly elevated risks of three major histologic types of liver tumors: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and hemangiosarcoma (HS) for Thorotrast exposures. In contrast, HS was the only liver tumor significantly associated with the lower alpha-particle doses experienced by the Russian workers. Excess cases per 1,000 persons exposed to Thorotrast were similar for the three liver cancer subtypes but lower for plutonium exposure. Odds ratios (OR) of HS and CC for Thorotrast were from 26 to 789 and from 1 to 31 times higher than those for HCC, respectively. ORs of liver cirrhosis for Thorotrast exposure ranged from 2.7 (95% confidence interval (CI): 2.2-3.4) to 6.7 (5.1-8.7).

Alpha Particles↗
PubMed2002

Dose responses for chromosome aberrations produced in noncycling primary human fibroblasts by alpha particles, and by gamma rays delivered at sublimiting low dose rates.

As the total dose of X or gamma rays is delivered at lower and lower rates, the yield of chromosome aberrations progressively diminishes. Simultaneously, the shape of the dose response changes from one exhibiting pronounced upward curvature at high dose rates to one approaching linearity at low dose rates. Although the maximum sparing effect caused by lowering the dose rate can be predicted from classical cytogenetic theory, it has yet to be verified experimentally. Here, noncycling normal human fibroblasts were exposed to graded doses of (137)Cs gamma rays at chronic dose rates of 6.3 and 2.8 cGy h(-1), dose rates that we reasoned should be lower than those required to achieve maximal sparing. This was indeed shown to be the case, after it was determined that the two chronic dose rates produced identical linear dose responses of 0.05 total aberrations per cell Gy(-1). Consistent with cytogenetic theory, this value was statistically indistinguishable from the linear coefficient derived from a fit to aberration frequencies produced by high-dose-rate exposure. Exposure to (238)Pu alpha particles also produced a linear dose response for total aberrations, whose slope-with respect to (137)Cs gamma rays as a reference radiation-implied a maximum RBE of 35 +/- 2.

Alpha Particles↗