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PubMed1990

Induction of chromosomal aberrations and sister chromatid exchanges by alpha particles in density-inhibited cultures of mouse 10T1/2 and 3T3 cells.

We examined the dose-response relationships for the induction of cell killing, chromosomal aberrations and sister chromatid exchanges (SCE) by 220 kV X-rays and 5.3 MeV alpha particles from a 238Pu source. The cells were irradiated in density-inhibited, confluent cultures. The D0 values for the X-ray and alpha particle survival curves were 1.7 Gy and 0.7 Gy, and the extrapolation numbers 2.5 and 1.0, respectively, for mouse 3T3 cells. Chromosomal aberrations increased linearly with dose for alpha-radiation and roughly with the square of dose for X-rays in 3T3 cells. At 37 per cent survival, 1.0 chromosomal aberration per cell was induced by X-rays and 1.7 per cell by alpha-radiation, but the fraction of cells without aberrations was similar. In confluent holding recovery experiments there was a 50 per cent reduction in X-ray-induced aberrations during the first 4 h of confluent holding. No decline in alpha-induced aberrations was observed with holding times up to 24 h. The dose-response relationship for the induction of SCE by X-rays increased linearly with doses up to 100 cGy in both 3T3 and 10T1/2 cells, then declined, reaching nearly background levels after 400 cGy. The induction of SCE increased rapidly in these cell lines with doses of 2.5-5.0 cGy of alpha-radiation, then declined. The relative biological effectiveness (RBE) was 15-25 for the induction of SCE by low doses (2.5-5.0 cGy) of alpha particles.

Alpha Particles↗

PubMed2002

Influence of dust loading on the alpha-particle energy resolution of continuous air monitors for thin deposits of radioactive aerosols.

Alpha-particle continuous air monitors must sometimes be operated in dusty environments where significant dust loading of the filter can be anticipated. It is important to understand how this dust loading affects the response of the continuous air monitors. Not only must a filter be changed if there is a reduction in airflow, but a change may be necessary if the energy resolution deteriorates and the continuous air monitor loses sensitivity and specificity for the radioactive aerosols of interest. A series of experiments were conducted to investigate alpha-particle energy resolution of continuous air monitor filters, particularly under dust loading conditions. Aerosol particles of various sizes were tagged with radon decay products to serve as surrogates for radioactive aerosols of interest such as plutonium or uranium. While the size of radioactive aerosols, filter type, and dust type affected the energy resolution, the thickness of an underlying (nonradioactive) dust layer did not show significant effect for the materials studied and a loading range of 0.01-10 mg x cm(-2). Our results indicate that it is possible for continuous air monitors to detect the release of radioactive aerosols with little deterioration in energy resolution under conditions of significant dust loading provided that the deposited layer of radioactive aerosols remains thin (< or = 0.1 mg x cm(-2)).

Aerosols↗

PubMed2004

Simulation of binary methods for the microdosimetric analysis of cell survival after alpha-particle irradiation: ability to distinguish between different models.

Analysis of cell survival after alpha-particle irradiation must account for the distribution in the amounts of energy deposited in each cell nucleus. Microdosimetric computations are usually used to determine these distributions. Irradiation with microbeams and other modern techniques has made these computations unnecessary for certain cell geometries. These techniques allow the survival of individual cells to be correlated with the amount of radiation delivered to individual cell nuclei. However, to maintain the individuality of data generated for each cell, new methods of analysis are required. In this study, we propose the use of binary methods. Each cell is regarded as a Bernoulli trial with a different probability for success (colony formation). Parameter values of the survival model are chosen to maximize the likelihood of the observed outcome. To evaluate this method, simulated data for 500, 5000 and 50,000 cells irradiated by alpha particles are analyzed along with the associated outcome for four different cell survival models. Each survival model has a different dependence on the radius of the cell nucleus. These results indicate that the model that was simulated has the highest likelihood value in all cases. However, the ability to distinguish between competing models is present only for a larger numbers of cells.

Alpha Particles↗

PubMed2006

Initial evaluation of (227)Th-p-benzyl-DOTA-rituximab for low-dose rate alpha-particle radioimmunotherapy.

Radioimmunotherapy has proven clinically effective in patients with non-Hodgkin's lymphoma. Radioimmunotherapy trials have so far been performed with beta-emitting isotopes. In contrast to beta-emitters, the shorter range and high linear energy transfer (LET) of alpha particles allow for more efficient and selective killing of individually targeted tumor cells. However, there are several obstacles to the use of alpha-particle immunotherapy, including problems with chelation chemistry and nontarget tissue toxicity. The alpha-emitting radioimmunoconjugate (227)Th-DOTA-p-benzyl-rituximab is a new potential anti-lymphoma agent that might overcome some of these difficulties. The present study explores the immunoreactivity, in vivo stability and biodistribution, as well as the effect on in vitro cell growth, of this novel radioimmunoconjugate. To evaluate in vivo stability, uptake in balb/c mice of the alpha-particle-emitting nuclide (227)Th alone, the chelated form, (227)Th-p-nitrobenzyl-DOTA and the radioimmunoconjugate (227)Th-DOTA-p-benzyl-rituximab was compared in a range of organs at increasing time points after injection. The immunoreactive fraction of (227)Th-DOTA-p-benzyl-rituximab was 56-65%. During the 28 days after injection of radioimmunoconjugate only, very modest amounts of the (227)Th had detached from DOTA-p-benzyl-rituximab, indicating a relevant stability in vivo. The half-life of (227)Th-DOTA-p-benzyl-rituximab in blood was 7.4 days. Incubation of lymphoma cells with (227)Th-DOTA-p-benzyl-rituximab resulted in a significant antigen-dependent inhibition of cell growth. The data presented here warrant further studies of (227)Th-DOTA-p-benzyl-rituximab.

Alpha Particles↗

PubMed1997

Radiation-induced transformation of SV40-immortalized human thyroid epithelial cells by single exposure to plutonium alpha-particles in vitro.

Human thyroid carcinomas have been induced following exposure of SV40-immortalized human thyroid epithelial cells in vitro to single doses (0.14 Gy to 1.57 Gy) of 3.26 MeV alpha-particles from a plutonium 238 source. Tumours were detected between 50 and 160 days following subcutaneous transplantation of the irradiated cells in athymic mice. No tumours were observed following transplantation of unirradiated cells. The relative biological effectiveness (RBE) of the alpha-particles, estimated from cell survival curves, was 4.8 at 50% survival and 3.3 at 5% survival. A first estimate of the RBE at peak tumour induction was 3.8. This system provides a means of studying the mechanisms of tumourigenesis in human thyroid epithelial cells induced by ionizing radiations, including tumours induced by single alpha particles such as from environmental natural radon and polonium and artificial plutonium and americium, and those induced by beta- or Auger-emissions from particular iodine isotopes.

Alpha Particles↗

PubMed2005

Experimental study of the cross-sections of alpha-particle induced reactions on 209Bi.

alpha-particle-induced nuclear reactions for generation of (211)At used in therapeutic nuclear medicine and possible contaminants were investigated with the stacked foil activation technique on natural bismuth targets up to E(alpha)=39 MeV. Excitation functions are reported for the reactions (209)Bi(alpha,2n)(211)At, (209)Bi(alpha,3n)(210)At and (209)Bi(alpha,x)(210)Po. Results obtained from direct alpha-emission measurements and gamma-spectra from decay products are compared and correspond well with earlier literature values. Thick target yields have been deduced from the experimental cross-sections and optimised production pathways for minimal contamination are presented. A comparison with the results of the theoretical model code ALICE-IPPE is discussed.

Journal Article↗

PubMed1998

An illustrative comparison of the event-size distributions for gamma-rays and alpha-particles in the whole mammalian cell nucleus.

PURPOSE: Recent laboratory studies of endpoints designated as due to radiation-induced genomic instability have cast doubt on the validity of the current theoretical framework. Under this framework extrapolations are made from directly determined risks of radiation-induced cancer to those circumstances for which no direct information exists, namely at low doses and dose rates at low LET and at low dose exposures to high LET radiations. Based upon an approach in which the 'state' of the genome, as exemplified by the pattern of gene expression, rather than the base sequence of the genomic DNA, is taken to be the origin of genomic stability, it is hypothesized that the critical factor determining the likelihood of destabilization by ionizing radiation is the dose to the whole cell nucleus. CALCULATIONS: The frequency distributions of event sizes from two qualities of radiation, low LET y-rays and 5 MeV alpha-particles, are compared with 60Co gamma-rays being taken to be a low LET reference radiation in determining the RBE of other radiation qualities. In the absence of measured event-size distributions for 60Co gamma-rays in spheres of similar size to the human cell nucleus, the 4.5 microm sphere has been chosen as illustrative. Frequency distributions for 5 MeV alpha-particles are derived, based on the idealized situation of a parallel beam of constant LET, with all particles traversing the sphere. RESULTS: When compared for a dose of 1 mGy the event-size (dose) distributions of the two qualities do not intersect. It is estimated that only 0.4% of the energy from the alpha-particles falls in the range of event sizes that can be produced by 60Co gamma-rays. CONCLUSIONS: Contrary to belief over the past 50 years, there is, in this low dose range, no 'continuum' based upon quantities such as LET or lineal energy that would provide a basis for extrapolation from measured RBE values. RBE is thus seen to be purely empirical. In addition, the potential to induce effects in bystander cells is not considered when deriving weighting factors for alpha-particles of the type that contribute significantly to public exposure to environmental radiation.

Alpha Particles↗

PubMed1981

[Combined action of UV light and alpha particles on yeast cells of different genotypes].

Combined action of ultraviolet (UV) light and alpha-particles on yeast cells of different genotypes has been studied. Under combined action, after small doses of UV-light the oscillated changes of cell survival were registered for wild-type cells independent of the ploidy and the sequence of application of radiations. Additive effect of high doses of UV-light and ionizing radiation was expressed for strains incapable of the recovery of damages induced by ionizing radiation. For yeast cells possessing such a capability, the synergistic interaction of damages inflicted by high doses of UV-light and alpha-particles was noted. Possible reasons of the observed cell responses are discussed.

Alpha Particles↗

PubMed1997

Radon and lung carcinogenesis: mutability of p53 codons 249 and 250 to 238Pu alpha-particles in human bronchial epithelial cells.

Radon-222, a decay product of uranium-238 and a source of high linear energy transfer (LET) alpha-particles, has been implicated in the increased risk of lung cancer in uranium miners as well as non-miners. p53 mutation spectrum studies of radon-associated lung cancer have failed to show any specific mutational hot spot with the exception of a single study in which 31% of squamous cell and large cell lung cancers from uranium miners showed a p53 codon 249 AGGarg --> ATGmet mutation. Although the results of laboratory studies indicate that double-strand breaks and deletions are the principal genetic alterations caused by alpha-particles, uncertainty still prevails in the description of DNA damage in radon-associated human lung cancer. In the present study, we have evaluated the mutability of p53 codons 249 and 250 to alpha-particles in normal human bronchial epithelial (NHBE) cells using a highly sensitive genotypic mutation assay. Exposure of NHBE cells to a total dose of 4 Gy (equivalent to approximately 1460 working level months in uranium mining) of high LET alpha-radiation induced codon 249 AGG --> AAG transitions and codon 250 CCC --> ACC transversions with absolute mutation frequencies of 3.6 x 10(-7) and 3.8 x 10(-7) respectively. This mutation spectrum is consistent with our previous report of radon-associated human lung cancer.

Adolescent↗

PubMed2004

Analysis of alpha-particle induced chromosome aberrations in human lymphocytes, using pan-centromeric and pan-telomeric probes.

PURPOSE: The aim of the present study has been the evaluation of the incomplete chromosome aberrations induced after alpha-particle irradiation by the simultaneous detection of all centromeres and telomeres present in human lymphocytes. Moreover, a study on the lengths of the different acentric fragments is presented. MATERIALS AND METHODS: Attached lymphocytes were irradiated at doses of 0.2, 0.5, 0.7 and 1 Gy using a 241Am source. Flourescent in-situ hybridization (FISH) techniques were applied using pan-centromeric and pan-telomeric probes. All abnormal cells were digitalised and analysed using a Cytovision FISH workstation. The description of all abnormalities observed, and the length of the acentric fragments was recorded. RESULTS: A total of 378 incomplete chromosomes plus incomplete acentrics was found. Cases with more than 92 telomeres were not detected. The ratio between total incomplete elements and multicentrics was 1.00. The total number of acentric (ace) fragments was 822; 57% of them were complete fragments ace (+,+), 26% incomplete fragments ace (+,-), and 17% interstitial fragments ace(-,-); the mean relative lengths were 2.91 +/- 0.06, 1.91 +/- 0.07 and 1.63 +/- 0.07, respectively. In all three cases a secondary peak in the length distribution was found, corresponding to a relative length between 3.5 and 4. CONCLUSION: The percentage of incomplete rejoinings is higher after alpha-particle exposure than that described previously for low-linear energy transfer (LET) radiation exposures. The results seem to indicate that compared to low-LET radiation, after alpha-particle exposure centromere-containing elements are more likely to be repaired.Many interstitial fragments are large linear forms that cannot be considered as non-distinguishable acentric rings.

Alpha Particles↗

PubMed1997

Neoplastic transformation and cytogenetic aberrations of rat tracheal epithelial cells induced by alpha-particle irradiation.

Primary rat tracheal epithelium (RTE) cells can be transformed in vitro by alpha-particles irradiation. One out of 3 isolated morphologically transformed colonies gave rise to an immortal cell line and ultimately became neoplastic by successive passaging. Cytogenetic analysis was performed on the cell line in order to understand how the specific chromosome alterations participate in the process of neoplastic transformation of RTE cells. The 5th, 18th, 39th passage cells and the colony cells isolated from soft agar (SA) culturing of the 40th passage cells were analyzed. The results showed that the 20th passage cells were nontumorigenic, but the 40th passage cells were tumorigenic. The increase of the length of the long arm of chromosome 15 (15q+) was frequent at the 5th passage (67.8%), especially in SA cells in which it occurred in a clonal fashion (100%). Therefore, 15q+ might be the critical gene lesion after alpha-particles irradiation. Monosomy of chromosome 8 that occurred frequently at passage 5 (54%) and 40 (53%) might be correlated with earlier transformation of RTE cells. In addition, three marker chromosomes (M1, M2 and M3) showed a passage-dependent increase. In particular M1 and M2 that were highly frequent at passage 39 (90%) suggested that they might play an important role in the process of cell transformation.

Alpha Particles↗

PubMed1995

Genetic control of RBE of alpha-particles for yeast cells irradiated in stationary and exponential phase of growth.

Survival curves of S. cerevisiae wild type and rad 50, 51, 52 and 54 mutants in haploid and diploid strains were measured after gamma-ray and alpha-particle irradiation in stationary and exponential phase of growth. The values of RBE of high-LET radiation, defined as the ratio of the mean lethal doses after sparsely and densely ionizing radiations, were determined. A correlation between the RBE of alpha-particles and cell repair capacity was supported for stationary phase cultures. For the first time, it was shown for all strains studied that at exponential phase of growth the RBE of alpha-particle-induced survival was decreased in comparison with that for stationary cells. For most mutant cells RBE was close to unity, i.e. cell radiosensitivity was almost identical for both sparsely and densely ionizing radiation. Possible reasons for the observed radiation responses are discussed.

Alpha Particles↗

PubMed1992

Transmission of chromosomal instability after plutonium alpha-particle irradiation.

When investigating the biological effects of ionizing radiation on the haemopoietic system, a confounding problem lies in possible differences between the biological effects of sparsely ionizing, low linear energy transfer radiation such as X-, beta- or gamma-rays, and densely ionizing, high linear energy transfer radiation such as alpha-particles. To address this problem we have developed novel techniques for studying haemopoietic cells irradiated with environmentally relevant doses of alpha-particles from a plutonium-238 source. Using a clonogenic culture system, cytogenetic aberrations in individual colonies of haemopoietic cells derived from irradiated stem cells have been studied. Exposure to alpha-particles (but not X-rays) produced a high frequency of non-clonal aberrations in the clonal descendants, compatible with alpha-emitters inducing lesions in stem cells that result in the transmission of chromosomal instability to their progeny. Such unexpected instability may have important implications for radiation leukaemogenesis.

Alpha Particles↗

PubMedDate not supplied

[Effect of alpha particles on bacteriophage T4].

Exponential survival curves were obtained for a dry film culture of bacteriophage T4 Br+ after exposure to both alpha-particles and gamma-quanta. Relative biological effectiveness of alpha-particles was 4.68 with respect to survival. The mutation spectrum after alpha-irradiation slightly differed from that produced by gamma-radiation.

Alpha Particles↗

PubMed1991

The dose-dependent fragmentation of chromatin in human fibroblasts by 3.5-MeV alpha particles from 238Pu: experimental and theoretical considerations pertaining to single-track effects.

The technique of premature chromosome condensation (PCC) was used to examine the dose-response relationship for the production of interphase (G0) chromosome fragments in noncycling normal human fibroblasts following exposure to 238Pu alpha particles, with special emphasis on the low-dose region. The dose response was convincingly linear from 0.2 to 3.0 Gy. Analysis of further data collected over a dose range of 1.1 to 22.4 cGy provided no evidence of deviation from linearity in this low-dose region. The fact that this lower dose range extends into the region where single-particle effects are dominant suggests that a linear extrapolation of this response from higher to lower doses is valid. Ratios of coefficients for the induction of fragments produced by 238Pu alpha particles versus 60Co gamma rays gave an RBE of 2.34 +/- 0.09. Distributions of fragments among 60Co gamma-irradiated cells were consistent with a Poisson expectation of random damage. In contrast, overdispersion appeared to be a general feature of 238Pu alpha-particle-induced fragmentation, a phenomenon explainable under the assumption that single-particle traversals are capable of producing multiple PCC fragments. Data obtained were used to estimate practical and theoretical lower-dose limits of detection of initial chromatin breaks provided by current PCC methodology.

Alpha Particles↗

PubMed1980

The induction of chromosome aberrations in human lymphocytes by in vitro irradiation with alpha-particles from plutonium-239.

The yields of unstable chromosome aberrations induced in human lymphocytes by alpha-particles from plutonium-239 have been measured. Plutonium citrate solution was mixed with heparinized blood so that doses of 13--160 rad were delivered in 24 hours. Dicentric aberration yields (Y) fitted best to the linear expression Y = 3 . 72 +/- 0 . 23 x 10(-3) rad-1. Inclusion of a 6 . 5 rad point resulting from a 1 . 7 hour irradiation raised the yield coefficient insignificantly to 3 . 75 +/- 0 . 24 x 10(-3). The aberration yields are in good agreement with data from curium-242 alpha-particles obtained in this laboratory but they are much lower than those obtained in two other laboratories. Reasons for this disagreement are examined.

Alpha Particles↗

PubMed2006

Improved determination of plutonium content and isotopic ratios in low activity samples by alpha-particle and underground L X-ray measurement.

The determination of the isotopic ratio of 239Pu and 240Pu by alpha-particle spectrometry is limited due to the small differences in the alpha-particle energies. But taking into account the differences in the L X-ray emission probabilities of the two plutonium isotopes, an additional L X-ray measurement allows the isotopic ratio of 239Pu and 240Pu to be determined. The sensitivity of this method can be improved, as described in this work, by performing the L X-ray measurement in an underground laboratory.

Algorithms↗

PubMed1992

The development of A [211At]-astatinated endoradiotherapeutic drug: Part I. Localization by alpha-particle autoradiography in a murine tumor model.

Alpha-particle track autoradiography has been used to define the in vivo cellular and intracellular distribution of radioactivity from the potential high linear energy transfer endoradiotherapeutic drug, 6-[211At]-astato-2-methyl-1,4-naphthoquinol bis(diphosphate) in tumor and relevant critical normal tissues of mice bearing a transplanted murine rectal carcinoma. A strikingly selective uptake of this compound into tumor cells, particularly into specific tumor cell nuclei, has been demonstrated. Its localization in certain tumor cells appears to depend on the presence of an onco-product, in this case an alkaline phosphatase isoenzyme, which is synthesized in some tumor cells and to which the compound targets. In curable tumors, it selectively concentrates in cells which may be regarded as tumor stem cells. There is low uptake into normal cells, particularly those in bone marrow, colon, and lung, where its sequestration is mainly extranuclear.

Alkaline Phosphatase↗