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PubMed1983

Microdosimetry of plutonium in lungs.

Chord length distributions for alveolar cells and cell nuclei were determined by superimposing computer-generated alpha-particle tracks on magnified images of randomly selected rat lung sections using the Quantitative Television Microscope. Specific energy distributions were then calculated by applying image analysis techniques. These microdosimetric calculations suggest that radiation carcinogenesis can be described in physical terms by the number of cells hit in a defined tissue volume, the specific energy distribution in these cells, the resulting number of non-lethally damaged cells which are susceptible to transformation, and their spatial distribution. If multicellular effects are involved in radiation carcinogenesis, then hot spots might be more carcinogenic than the uniform distribution at low doses and less carcinogenic at high doses.

Alpha Particles↗

PubMed1994

Alterations in oncogene expression and radiosensitivity in the most frequently used SV40-transformed human skin fibroblasts.

In comparison with primary cell cultures, SV40-transformed human skin fibroblasts, either from healthy donors or from patients suffering from ataxia-telangiectasia (AT) or xeroderma pigmentosum, are more resistant to the cytotoxic action of low LET 60cobalt gamma-rays as well as to high LET alpha-particles. Resistance factors calculated from D10's lie between 1.4 and 2.0. Northern blot analysis reveals spontaneous overexpression of the oncogenes c-myc, Ki-ras and c-raf and of the tumour suppressor gene p53 as a consequence of SV40 transformation. For c-myc, the increased expression is due to gene amplification and gene rearrangement. An even further increase in the expression of c-myc has been found for AT cells (AT5BI-VA) after moderate doses of 60cobalt gamma-irradiation. A possible correlation between SV40-induced changes in gene expression and cellular radioresistance is discussed.

Alpha Particles↗

PubMed1995

Heavy ion-induced DNA double-strand breaks with yeast as a model system.

Cells of diploid yeast, Saccharomyces cerevisiae, were exposed to a variety of energetic heavy ions (provided by the UNILAC facility at the Gesellschaft für Schwerionenforschung, GSI), 241Am alpha-particles and 80-keV x-rays after which they were assessed for DNA double-strand breaks (DSB) using either the neutral sedimentation or the pulsed-field gel electrophoresis (PFGE) technique. Both yielded comparable results. The DSB production cross-sections are compared with inactivation studies performed for the same cells under identical conditions. The measurements show that with lighter ions DSB induction cross-sections increase with linear energy transfer (LET), but the situation is less clear with the heavier ions. A close parallelism was found between DSB induction and cell inactivation in these yeast cells.

Alpha Particles↗

PubMed2004

Detection of chromosomal instability in alpha-irradiated and bystander human fibroblasts.

There is increasing evidence biological responses to ionizing radiation are not confined to those cells that are directly hit, but may be seen in the progeny at subsequent generations (genomic instability) and in non-irradiated neighbors of irradiated cells (bystander effects). These so called non-targeted phenomena would have significant contributions to radiation-induced carcinogenesis, especially at low doses where only a limited number of cells in a population are directed hit. Here we present data using a co-culturing protocol examining chromosomal instability in alpha-irradiated and bystander human fibroblasts BJ1-htert. At the first cell division following exposure to 0.1 and 1Gy alpha-particles, irradiated populations demonstrated a dose dependent increase in chromosome-type aberrations. At this time bystander BJ1-htert populations demonstrated elevated chromatid-type aberrations when compared to controls. Irradiated and bystander populations were also analyzed for chromosomal aberrations as a function of time post-irradiation. When considered over 25 doublings, all irradiated and bystander populations had significantly higher frequencies of chromatid aberrations when compared to controls (2-3-fold over controls) and were not dependent on dose. The results presented here support the link between the radiation-induced phenomena of genomic instability and the bystander effect.

Alpha Particles↗

PubMed2000

Experimental partial and total kerma coefficients for carbon deduced from microscopic cross sections at incident neutron energies below 75 MeV.

The double-differential cross sections for proton, deuteron, triton and alpha particle production in fast neutron induced reactions on carbon have been measured at several neutron energies from 25 to 75 MeV in the angular range from 20 degrees to 160 degrees. Experimental energy-differential, angle-differential and total cross sections are deduced, and consequently the partial and total kerma coefficients. The obtained experimental partial kerma coefficients are extrapolated down to the threshold energy of each measured reaction channel. Results on the experimental double differential, energy-differential and total cross sections are briefly presented. The deduced partial and total kerma coefficients of the present work are compared with previous measurements and theoretical predictions.

Alpha Particles↗

PubMed2006

A microbeam study of DNA double-strand breaks in bystander primary human fibroblasts.

Radiation-induced bystander effect has been well documented. However, the mechanisms are poorly understood. How we incorporate this effect into the classical models of risk assessment remains an open question. Here, the induction of bystander effect was studied by assessing DNA double-strand break (DSB) formation in situ with the rapid and sensitive gamma-H2AX focus formation assay. Utilising the Columbia University single-cell microbeam system to deliver 2 or 20 individual alpha particles to selected cell nuclei in a precisely known proportion of cells in a population, the induced DNA DSB incidences were quantified 30 min and 18 h post-IR. The increase in DNA DSB incidence in bystander cells lacked of a linear dose response indicating that neither the dose of irradiation nor proportion of irradiated cells in a population, is a critical parameter. This study confirms a binary all-or-nothing model of triggering the bystander response. The delay and persistence of the bystander response suggests a different mechanism of DSB induction in bystander cells than in directly irradiated cells.

Alpha Particles↗

PubMed2005

Determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in drinking water using a single sample preparation procedure.

The current federal and New Jersey State regulations have greatly increased the number of gross alpha and radium tests for public and private drinking water supplies. The determination of radium isotopes in water generally involves lengthy and complicated processes. In this study, a new approach is presented for the determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in water samples. The method includes a single sample preparation procedure followed by alpha counting and gamma-ray spectroscopy. The sample preparation technique incorporates an EPA-approved co-precipitation methodology for gross alpha determination with a few alterations and improvements. Using 3-L aliquots of sample, spiked with 133Ba tracer, the alpha-emitting radionuclides are isolated by a BaSO4 and Fe(OH)3 co-precipitation scheme. First the gross alpha-particle activity of the sample is measured with a low-background gas-flow proportional counter, followed by radium isotopes assay by gamma-ray spectroscopy, using the same prepared sample. Gamma-ray determination of 133Ba tracer is used to assess the radium chemical recovery. The 224Ra, 226Ra, and 228Ra activities in the sample are measured through their gamma-ray-emitting decay products, 212Pb, 214Pb/214Bi, and 228Ac, respectively. In cases where 224Ra determination is required, the gamma-ray counting should be performed within 2-4 d from sample collection. To measure 226Ra activity in the sample, the gamma-ray spectroscopy can be repeated 21 d after sample preparation to ensure that 226Ra and its progeny have reached the equilibrium state. At this point, the 228Ac equilibration with parent 228Ra is already established. Analysis of aliquots of de-ionized water spiked with NIST-traceable 230Th, 224Ra, 226Ra, and 228Ra standards demonstrated the accuracy and precision of this method. Various performance evaluation samples were also assayed for gross alpha as well as radium isotope activity determination using this procedure and the results were in close agreement with the assigned values. In addition, method comparison results of actual sample analyses agreed well with the ones performed using EPA-approved procedures. With a 3-L sample aliquot and 1,000-min counting time, the average gross alpha minimum detectable concentration (MDC) was about 0.002 Bq L(-1). The average MDC's for 224Ra, 226Ra, and 228Ra were 0.034 Bq L(-1), 0.017 Bq L(-1), and 0.036 Bq L(-1), respectively, based on a 3-L sample aliquot, 85% chemical yield, 40% intrinsic Ge detector, and 1,000-min count time. This method combines and simplifies the analytical procedures and reduces labor while achieving the precision, accuracy, and minimum detection limit requirements of EPA regulations.

Alpha Particles↗

PubMed1996

DNA double strand break production and rejoining in V79 cells irradiated with light ions.

Low energy protons and other densely ionizing light ions are known to have RBE>1 for cellular end points relevant for stochastic and deterministic effects. The occurrence of a close relationship between them and induction of DNA dsb is still a matter of debate. We studied the production of DNA dsb in V79 cells irradiated with low energy protons having LET values ranging from 11 to 31 keV/micrometer, i.e. in the energy range characteristic of the Bragg peak, using the sedimentation technique. We found that the initial yield of dsb is quite insensitive to proton LET and not significantly higher than that observed with X-rays, in agreement with recent data on V79 cells irradiated with alpha particles of various LET up to 120 keV/micrometer. By contrast, RBE for cell inactivation and for mutation induction rises with the proton LET. In experiments aimed at evaluating the rejoining of dsb after proton irradiation we found that the amount of dsb left unrepaired after 120 min incubation is higher for protons than for sparsely ionizing radiation. These results indicate that dsb are not homogeneous with respect to repair and give support to the hypothesis that increasing LET leads to an increase in the complexity of DNA lesions with a consequent decrease in their repairability.

Alpha Particles↗

PubMed2004

Sterically stabilized liposomes as a carrier for alpha-emitting radium and actinium radionuclides.

The alpha-particle emitting radionuclides (223)Ra (t(1/2) = 11.4 d), (224)Ra (t(1/2) = 3.6 d), and (225)Ac(t(1/2) = 10.0 d) may have a broad application in targeted radiotherapy provided that they could be linked to vehicles with tumor affinity. The potential usefulness of liposomes as carriers was studied in the present work. Radium and actinium radionuclides could be loaded in good yields into sterically stabilized liposomes. Subsequent coating of the liposomes with a folate-F(ab')(2) construct yielded a product with affinity towards tumor cells expressing folate receptors. Radionuclide loaded liposomes showed excellent stability in serum in vitro.

Actinium↗

PubMed2004

Measurement of parameters of tracks in CR-39 detector from replicas.

In determining the etched track rate in solid-state nuclear track detectors, track lengths should be determined accurately. A method based on surface profilometry is proposed to determine the track lengths in CR-39 detectors through measurements of their replicas. Tracks from alpha particles with an incident energy of 4 MeV have been chosen to demonstrate the method. After irradiation and chemical etching, resin replicas were made from the tracks, of which the heights were measured by the Form Talysurf PGI Profilometer. The results showed that the surface of the replicas were smooth and the heights of the replicas were uniform, so the replicating fluid should have filled the tracks completely and the replicas truly reflected the dimensions of the tracks. The heights of the replicas were conveniently determined from the lateral view of the replicas generated by the Form Talysurf PGI Profilometer.

Alpha Particles↗

PubMed1984

The dosimetry of bone incorporating alpha-emitting radionuclides.

The previous work on the dosimetry of alpha-emitting radionuclides incorporated in bone is briefly reviewed. The application of cavity ionisation theory to problems of bone dosimetry is propounded and recent developments of the cavity theory for alpha particle fields are applied to bone dosimetry problems. The mean marrow dose over a large range of bone cavity size calculated by a simple theory using a mean chord length to characterise a cavity is compared with results of a more elaborate theory employing the chord length distribution for a sphere. The difference is not great. The influence of the shape of the cavity is explored by considering cylindrical cavities of different elongation. Data are presented for both volume-seeking and surface-seeking radioactive nuclides. The endosteal dose to a 10 mu layer is calculated as a function of cavity size for both volume-seeking and surface-seeking radioactive nuclides. The endosteal dose is also calculated for a surface seeker as a function of endosteal layer thickness. Finally, the results of these calculations are shown to be generally in good agreement with those of the calculations of earlier workers. It is concluded that a simple and reliable method of calculating the mean marrow dose and endosteal dose for both volume- and surface-seeking alpha emitters has been established.

Alpha Particles↗

PubMed2006

Allelic imbalance at 11q23-q24 chromosome associated with estrogen and radiation-induced breast cancer progression.

Multiple genetic alterations are common in cancers including those of the breast. The mechanisms leading to these alterations such as point mutations, gene amplifications, deletions and replication error are often associated with frequent and consistent loss of heterozygosity (LOH) or microsatellite instability (MSI). Several cytological and molecular studies have shown high frequency loss of genetic information on the long arm of chromosome 11 (i.e., 11q) in various primary breast cancers. In the present study allelic alterations in a refined position on the long arm of chromosome 11 were studied to identify the spectrum of induced damage at different stages of malignant transformation of MCF-10F cell lines after exposure to high-LET radiation using alpha-particles and exposure to estradiol by using PCR-single strand conformation polymorphism (SSCP) and fluorescence in situ hybridization (FISH) analysis. Microsatellite markers were selected from chromosome 11 (11q23-q24 loci) and it was found that frequency of allelic imbalance occurs at different stages of tumor progression with a range of 15-45% depending on the marker studied. These results strongly suggested the presence of several tumor suppressor genes in this critical region of chromosome 11 (11q23-q24). It also represents the first indication of allele loss at these loci in human breast epithelial cells induced by radiation and estrogen treatment suggesting a potential interventional target in breast carcinogenesis.

Alpha Particles↗

PubMedDate not supplied

Primary and secondary measurements of 222Rn.

In the past few years, a primary measurement system has been established at the PTB allowing absolute measurements of 222Rn. The activity can be determined by counting the emitted alpha particles in a defined solid angle after condensing the radon at a cold point under vacuum conditions. This primary measurement system is connected to a solid 226Ra source, where 222Rn can be produced up to an activity of about 2MBq. After the measurement, radon can be completely transferred into a glass bulb or a stainless steel cylinder for use as a transfer standard. The results of the measurements, the uncertainties and the realization of the primary measurement system are described. For quality assurance and fast determination of radon activity, a secondary measurement system with an NaI(Tl) detector is also used. Together, both systems provide a reliable tool for the production of gaseous 222Rn activity standards with relative uncertainties of less than 1%.

Alpha Particles↗

PubMed1981

Mammalian cell survival and radiation quality: analysis with allowance for delta tracks.

The RBE for mammalian cell survival is analysed in relation to the distribution of LET. Complex target theory is described, together with a procedure for applying LET distributions to experimental findings in order to estimate the modes of cellular inactivation. Track segment theory is shown to have previously unrecognised limitations. The stepwise method is adopted to calculate the LET distributions for the radiations (alpha-particles, deuterons and x-rays) used by Barendsen et al (1966) in their study of the survival of T1 cells of human origin. Satisfactory fits of theory to experiment are obtained. Three distinctive modes of cellular inactivation, with independent energy transfers (direct and indirect) to complex targets comprising 2, 4 adn 6 elements respectively, appear to be involved overall. At 'low dose', no contribution from the 2-transfer-mode can be discerned; only this mode is reparable. Saturation cross-sections (at high LET) for the 2- and 4-transfer-, but not the 6-transfer-mode, are oxygen-dependent. All three modes of inactivation might entail unrepaired double strand breaks and/or some form of mutation in DNA, at 1, 2 and 3 vulnerable sections, respectively.

Alpha Particles↗

PubMed1992

Constraints on energy deposition and target size of multiply damaged sites associated with DNA double-strand breaks.

We suggest that the observed experimental data on relative double-strand break (dsb) yield as a function of radiation quality can act as valuable constraints in defining the type of energy deposition which causes this basic lesion in radiation biology. Both heavy-ion and alpha-particle data show sufficient trends for quantitative comparisons with calculation to be made. We use the technique of track-structure simulation and search for energy-deposition clusters (containing at least a given number of ionizations in a given diameter) whose relative frequencies (compared to sparsely ionizing radiation) correlate with the relative biological effects (RBEs) for dsb induction. We conclude that locally multiply damaged sites (LMDS) which cause dsb are probably energy depositions of at least two to five ionizations localized, respectively, in sites of diameters of 1-4 nm. Although our derived cluster sizes should be viewed in light of the quality of the experimental data and uncertainties in the computer simulations at the nanometre level, it is unlikely that these estimates of cluster sizes would change greatly.

Alpha Particles↗

PubMed2002

Relative biological effectiveness of light ions in human tumoural cell lines: role of protein p53.

Protons and alpha particles of high linear energy transfer (LET) have shown an increased relative biological effectiveness (RBE) with respect to X/gamma rays for several cellular and molecular endpoints in different in vitro cell systems. To contribute to understanding the biochemical mechanisms involved in the increased effectiveness of high LET radiation, an extensive study has been designed. The present work reports the preliminary result of this study on two human tumoural cell lines, DLD1 and HCT116, (with different p53 status), which indicate that for these cell lines, p53 does not appear to take a part in the response to radiation induced DNA damage, suggesting an alternative p53-independent pathway and a cell biochemical mechanism dependent on the cell type.

Alpha Particles↗

PubMed1985

Effect of dose rate on the induction of experimental lung cancer in hamsters by alpha radiation.

The effect of dose rate on the induction of lung cancer in Syrian hamsters by 5.3 MeV alpha particles was examined by varying the number of weekly intratracheal instillations of carrier-free 210Po. By this technique, most of the radiation dose to the lungs was delivered over intervals ranging from 10 to 120 days. Protraction of exposure over 120 days was slightly more carcinogenic at lower total lung doses (24 rad), but slightly less carcinogenic at higher doses (240 rad), than exposure limited to a 10-day interval. No synergism was observed between very low radiation exposures (2.4 rad) and simultaneously administered benzo[a]pyrene. The carcinogenic effect of a single intratracheal instillation of 210Po in isotonic saline was markedly enhanced by subsequent weekly instillations of 0.2 ml of saline alone, emphasizing the importance of noncarcinogenic secondary factors in the expression of radiation-induced lung cancer.

Alpha Particles↗

PubMed2004

Cell death triggered by alpha-emitting 213Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death.

PURPOSE: Radioimmunotherapy with alpha-particle-emitting nuclides, such as 213Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by 213Bi-immunoconjugates. METHODS: Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of 213Bi-d9MAb targeting d9-E-cadherin and 213Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as 213Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and 213Bi-d9MAb was analysed via Western blotting. RESULTS: Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with 213Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of alpha-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific 213Bi-d9MAb compared with unspecific 213Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound 213Bi-immunoconjugates per cell exceeded 2 x 10(4), most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by 213Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. CONCLUSION: 213Bi-immunoconjugates seem to induce a mode of cell death different from apoptosis in HSC45-M2 cells.

Alpha Particles↗