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At least 19 recordsLinked to original sources
PubMed1991

Radiobiology of alpha particles. III. Cell inactivation by alpha-particle traversals of the cell nucleus.

Cell inactivation after exposure to collimated 3.5-MeV alpha particles in three hamster cell lines, V79, CHO-10B, and HS-23, one mouse cell line, C3H 10T1/2, and a human skin fibroblast cell line were studied. Several parameters were investigated for each cell line. Theoretical calculations were performed to find the distribution of energy deposited in the nuclear volume for each cell line. The mean number of alpha-particle traversals required to induce a lethal lesion varied between two for HS-23 cells and six for C3H 10T1/2 cells. The number of traversals per unit area and the total track length of alpha particles that inactivated a cell were found to be nearly constant for the hamster and mouse cell lines. These quantities were found to be lower for the human skin fibroblast cell line. The RBE values for all cell lines were found to be about 3.8 at 10% survival. Thus cell lines that are more sensitive to alpha radiation are also more sensitive to gamma radiation. The average number of alpha-particle traversals producing a single lethal lesion is greater than one. The passages of alpha particles through the cell nucleus that do not kill the cell may lead to carcinogenic effects.

Alpha Particles↗
PubMed1991

Radiobiology of alpha particles. II. Dosimetry of low-energy alpha particles using parallel-plate ionization chambers and a surface barrier detector.

Three small parallel-plate ionization chambers were developed for measuring dose rates, of primarily low-energy alpha particles in the energy range 0.4-3.5 MeV, at a defined cell-Mylar interface. Spectral energy distributions of these alpha particles were also measured at the same position using a specially designed small-area silicon surface barrier detector. Dose rates were derived from the spectral distributions and compared with those derived from the ionization chambers. Different alpha-particle energies were obtained using a 144-MBq 238Pu collimated source and a variety of Mylar moderator foils of different thicknesses. These measurements, extended to mean alpha-particle energies as low as 0.4 MeV, will enable us to correlate radiobiological data with effects of alpha particles terminating in different regions of cell nuclei.

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PubMed1991

A device for in vitro irradiation with alpha-particles using an alpha-emitting radioactive source.

A device to irradiate a monolayer of cultured cells with alpha-particles using an Am-241 alpha-source (33.4 MBq) was designed to investigate RBEs of alpha-particles in cell killing, induction of chromosome aberration, mutagenic changes and transformation. This device can be used conveniently in a common laboratory by a small number of researchers without any limitation of machine time. The device performs as follows: (1) The energy of alpha-particles at the entrance of the cell layer is 3.20 MeV with a standard deviation of 0.25 MeV, (2) the incident angle to the cell layer is 82.8 degrees with a standard deviation of 3.2 degrees, (3) the fluence rate is 4.7 x 10(5) cm-2.min-1, (4) the average LET infinity for a cell layer 5 microns thick is 138 keV/micron, (5) the average dose rate for a cell layer 5 microns thick is 0.10 Gy/min., (6) a temperature and CO2 concentration conducive to cell cultivation are maintained during irradiation.

Alpha Particles↗
PubMed1988

Radioimmunotherapy with alpha-particle-emitting immunoconjugates.

Alpha particles are energetic short-range ions whose higher linear energy transfer produces extreme cytotoxicity. An alpha-particle-emitting radioimmunoconjugate consisting of a bismuth-212-labeled monoclonal immunoglobulin M specific for the murine T cell/neuroectodermal surface antigen Thy 1.2 was prepared. Analysis in vitro showed that the radioimmunoconjugate was selectively cytotoxic to a Thy 1.2+ EL-4 murine tumor cell line. Approximately three bismuth-212-labeled immunoconjugates per target cell reduced the uptake of [3H]thymidine by the EL-4 target cells to background levels. Mice inoculated intraperitoneally with EL-4 cells were cured of their ascites after intraperitoneal injection of 150 microcuries of the antigen-specific radioimmunoconjugate, suggesting a possible role for such conjugates in intracavitary cancer therapy.

Alpha Particles↗
PubMed1991

Response of X-ray-sensitive CHO mutant cells (xrs-6c) to radiation. II. Relationship between cell survival and the induction of chromosomal damage with low doses of alpha particles.

The induction of cytotoxicity, chromosomal aberrations, and sister chromatid exchanges (SCEs) was measured in CHO K-1c cells and in isogenic X-ray-sensitive mutant xrs-6c cells that had been irradiated with X rays and alpha particles in isoleucine-deficient alpha-minimal essential medium in G1 phase of the cell cycle. There was a noticeable shoulder region on the survival curve for CHO K-1c cells irradiated with very low doses of alpha particles, whereas this feature was absent for xrs-6c cells with alpha-particle doses as low as 0.5 cGy. Higher frequencies of chromatid-type aberrations were induced in G1-phase xrs-6c cells than in G1-phase CHO K-1c cells by both gamma- and alpha-particle irradiation. Induction of nonlethal chromosomal aberrations was observed following exposure to 2-6 cGy of alpha particles, doses yielding 97-100% cell survival. Irradiation with 0.5 cGy of alpha particles induced SCE; nearly 60% of irradiated cells contained significantly increased levels of SCE. However, only 3% of the nuclei of cells exposed to 0.5 cGy of alpha-particle radiation were actually traversed by an alpha particle. The observation that a large fraction of cells apparently survive exposure to very low doses of alpha-particle radiation with persistent genetic damage manifested by both chromosomal aberrations and SCEs may have important implications for the carcinogenic hazards of high-LET radiation.

Alpha Particles↗
PubMed1990

Response of cultured human airway epithelial cells to X-rays and energetic alpha-particles.

Radon and its progeny, which emit alpha-particles during decay, may play an important role in inducing human lung cancer. To gain a better understanding of the biological effects of alpha-particles in human lung we studied the response of cultured human airway epithelial cells to X-rays and monoenergetic helium ions. Our experimental results indicated that the radiation response of primary cultures was similar to that for airway epithelial cells that were transformed with a plasmid containing an origin-defective SV40 virus. The RBE for cell inactivation determined by the ratio of D0 for X-rays to that for 8 MeV helium ions was 1.8-2.2. The cross-section for helium ions, calculated from the D0 value, was about 24 microm 2 for cells of the primary culture. This cross-section is significantly smaller than the average geometric nuclear area (approximately 180 microms 2), suggesting that an average of 7.5 alpha-particles (8 MeV helium ions) per cell nucleus are needed to induce a lethal lesion.

Alpha Particles↗
PubMed1990

A comparative study of rejoining of DNA double-strand breaks in yeast irradiated with 3.5 MeV alpha-particles or with 30 MeV electrons.

Yeast cells were irradiated with 3.5 MeV alpha-particles and 30 MeV electrons, as reference radiation. The kinetics of DNA double-strand break (dsb) rejoining during incubation of cells under non-growth conditions (PLDR conditions) were measured using the neutral sedimentation technique. A monophasic kinetic was found after irradiation of cells with alpha-particles, with a dose-independent t1/2 value of about 13 h. The kinetics of rejoining of dsb induced by 30 MeV electrons was found to be biphasic, with dose-independent t1/2 values of 3.8 h for the initial and of about 11 h for the slow component. The fraction of the slow component was, however, dose-dependent. These kinetics were measured for both types of radiation at doses yielding high surviving fractions (5% up to 100%). Dsb are induced linearly with dose of both radiations. The RBE value of alpha-particles was found to be 2.5 for initial dsb. The RBE of alpha-particles increased as a consequence of dsb rejoining. This increase in RBE value suggests that DSB may be primary lesions for chromosome aberrations, cellular inactivation and oncogenic transformation of mammalian cells which all exhibit high RBE values of alpha-particles.

Alpha Particles↗
PubMed1990

The combined effects of alpha-particles and X-rays on cell killing and micronuclei induction in lung epithelial cells.

Understanding how cellular damage produced by high-linear energy transfer (LET) radiation interacts with that produced by low-LET is important both in radiation therapy and in evaluating risk. To study such interactions, rat lung epithelial cells (LEC) were grown on Mylar films and exposed to both X-rays and alpha-particles, separately or simultaneously. Cell killing, and the numbers of binucleated cells and micronuclei, were measured as indicators of damage. X-rays and alpha-particles given separately caused dose-related increases in cell cycle time, with alpha-particles producing greater mitotic delay than X-rays. Damage from alpha-particles and X-rays given simultaneously did not interact to alter further the cell cycle. Cell survival data following exposure to X-rays and alpha-particles, combined or individually, were fitted by linear-quadratic models. Survival curves following exposure to alpha-particles only, or to 1.0 Gy alpha-particles plus graded X-ray doses, were adequately described using only the linear (alpha) term of a linear-quadratic model with alpha coefficients of 0.9 +/- 0.04 and 1.03 +/- 0.18 Gy-1, respectively. Survival following exposure to X-rays only or to 0.06 Gy alpha-particles combined with X-rays was best fitted using both alpha and beta terms of the linear-quadratic model (0.12 +/- 0.03)D + (0.007 +/- 0.002)D2 and (0.57 +/- 0.08)D + (0.3 +/- 0.02)D2, respectively. The numbers of micronuclei produced by exposure to alpha-particles or X-rays alone increased linearly with dose, with slopes of 0.48 +/- 0.07 and 0.19 +/- 0.05 micronuclei/binucleated cell per Gy for alpha and X-rays, respectively. Simultaneous exposure to graded levels of X-rays and a constant alpha dose of either 1.0 or 0.06 Gy increased micronuclei frequency, with a slope of 0.74 +/- 0.05 or 0.58 +/- 0.04 micronuclei/binucleated cell per Gy, respectively. These slopes are similar to that produced by alpha-particles alone. These studies demonstrated that both cell killing and the induction of micronuclei were increased by combined exposures compared with that predicted for separate exposures.

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PubMed1992

Inactivation of C3H 10T1/2 cells by monoenergetic high LET alpha-particles.

Inactivation of mouse C3H 10T1/2 cells in plateau-phase (7.8 x 10(4) cells/cm2) was studied by using alpha-particles from the irradiation facility installed for radiobiological experiments at the 3 MV Tandem accelerator, University of Naples. Silicon detectors and CR39 plastic track detectors were employed for dosimetric purposes. The cells were exposed to high LET monoenergetic alpha-particles (energy of 1.8 MeV at the centre of the cell nucleus, track-averaged LET of 177 keV/micron and dose-rate of 1.1 Gy/min) and low-LET 80 kVp X-rays. The X-ray survival curve showed a significant shoulder (alpha/beta = 9 Gy) while the survival curve for alpha-particles was close to exponential. The mean lethal dose of alpha-particles was 0.77 +/- 0.02 Gy and the RBE was 5.2 at 80% survival and 3.0 at 5% survival. Survival of exponentially growing cells (2 x 10(4) cells/cm2) following irradiation with the alpha-particle beam is also reported. The nuclear areas of 10T1/2 cells were measured as 299 +/- 9 micron 2 and 250 +/- 8 micron 2 for cells in log phase and plateau phase, respectively. The inactivation cross-section, obtained from the mean lethal dose, was 34 micron 2 and 37 micron 2 for cells in log phase and plateau phase, respectively. These values appear to be the maximum measured values for the inactivation cross-section of 10T1/2 cells as a function of the alpha-particle LET. This saturation cross-section is very similar to the saturation values reported in the literature for other mammalian cell lines.

Alpha Particles↗
PubMed1979

Elemental analysis of bone mineral by backscattering of alpha particles.

Backscattering of 2 MeV alpha particles has been applied for the first time to studies of the inorganic substances of human bone. Bone samples taken from the femoral shaft (dense bone) and iliac crest (spongy bone) of 18 cadavers were analysed for the calcium, phosphorus and oxygen content, after lyophilisation and heating for 1.5 h at 500 degrees C to remove water and organic material. The backscattering method produces a spectrum in which all the elements present in the sample except hydrogen can be seen at once. The reproducibility of the measurements was less than 2%. No previous studies were found in the literature of the measurement of elemental oxygen in bone samples. Ca/P ratios varied from 1.97 to 2.47, Ca/O ratios from 0.76 to 0.91 and P/O ratios from 0.34 to 0.41, the latter two being about 10--15% lower than expected if bone mineral were hydroxyapatite (Ca/O = 0.96 and P/O = 0.44). The results are consistent with previous work on Ca/P ratios but the low Ca/O and P/O ratios could not be explained without postulation of crystal or hydroxyl water in bone mineral. Support for the explanation was gained by differential gravimetric and thermal analysis.

Alpha Particles↗
PubMed1991

A versatile plutonium-238 irradiator for radiobiological studies with alpha-particles.

A versatile irradiator has been constructed for in vitro irradiation of mammalian cells with alpha-particles of well-defined energy, LET, direction, dose and dose rate. It is based on approximately 1.2 x 10(9) Bq of 238Pu (on a platinum disc) contained in a He-filled chamber. In a standard configuration, monolayers of cells grown in 10 Hostaphan-based dishes are irradiated with 3.26 +/- 0.22 MeV alpha-particles (LET 121 keV microns-1) at selectable dose rates from approximately 2 Gy min-1 down to less than 10(-4) Gy min-1 (i.e. fluence rates of 1 x 10(7) cm-2 min-1 to 3 x 10(2) cm-2 min-1). Single dishes can be irradiated at dose rates up to 24 Gy min-1 (fluence rate 1 x 10(8) cm-2 min-1). Incident energy and LET can be varied from 0.8 to 4.2 MeV and 266 to 102 keV microns-1, respectively. The irradiator has full incubation and gassing facilities for protracted irradiations. The irradiator is particularly suitable for in vitro analytical studies of the biological effects of alpha-particles of energies and LETs similar to those which cells may receive in vivo from radionuclides such as radon and the actinides. It has been used successfully for investigations of a variety of alpha-particle-induced effects in different cell types irradiated either as attached monolayers or as very thin suspensions.

Alpha Particles↗
PubMed1991

Mutations induced by ionizing radiation in a plasmid replicated in human cells. II. Sequence analysis of alpha-particle-induced point mutations.

The human shuttle plasmid pZ189, containing the Escherichia coli supF gene as the mutational target, was irradiated in vitro with 210Po alpha particles and transfected into human lymphoblastoid cells. Plasmids which were replicated in human cells were recovered and those containing mutant supF genes were isolated by phenotypic screening in E. coli. The mutations were characterized by sequencing the tRNA gene. The mutant frequency increased linearly with the alpha-particle dose and, at 259 Gy, it was 16 times (0.29%) that observed in unirradiated controls (0.018%). The distribution of alpha-particle-induced point mutations was highly nonrandom and similar to that observed in the unirradiated or X-irradiated plasmid DNAs. The majority of the mutations were G.C----A.T transitions and occurred selectively at most 5'-TC (3'-AG) and 5'-CC (3'-GG) sequences. For the unirradiated control DNA, these mutations at C's (G's) were preferentially located in the nontranscribed strand, similar to the observation previously made for mutations in X-irradiated DNA. Such a strand bias was not observed for mutations in the alpha-particle-irradiated DNA. The data suggest that, although similar types of point mutations are induced in unirradiated, X-irradiated, and alpha-particle-irradiated DNAs, the mechanisms of their induction and the exact nature of the lesions involved may be quite different.

Alpha Particles↗
PubMed1988

DNA double-strand break repair determines the RBE of alpha-particles.

Radiation-induced DNA double-strand breaks (dsb) were studied in Ehrlich ascites tumour cells (EATC) by sedimentation in neutral sucrose gradients at low centrifuge speed. Dsb induction was found to be linear with dose with a frequency of: ndsbmr-1D-1 = (11.7 +/- 2) x 10(-12)Gy-1 for 140 kV X-rays and ndsbmr-1D-1 = (19.1 +/- 4) x 10(-12)Gy-1 for 3.4 MeV 241Am-alpha-particles. Postirradiation incubation of cells under non-growth conditions leads to repair of dsb, reaching a maximum after trep = 24 h. More than 97 per cent of dsb were repaired after an X-ray dose of 25 Gy. The number of residual dsb was found to be a linear-quadratic function of dose: nresmr-1 = (0.0161 +/- 0.0008) x 10(-12)Gy-2D2 for X-rays and nresmr-1 = (1.2 +/- 0.7) x 10(-12)Gy-1D + (0.105 +/- 0.017) x 10(-12)Gy-2D2 for alpha-particles. Thus, after cellular repair the RBE value of alpha-particles was increased from RBE = 1.6 +/- 0.4 (induction of dsb) to a dose-dependent value of RBE = 2.7 +/- 0.4 (at 100 Gy alpha-particles) to 3.8 +/- 1.2 (at 10 Gy alpha-particles) for residual dsb. From the data presented it is concluded that residual dsb are a major cause for loss of the reproductive capacity of EATC after irradiation with X-rays as well as alpha-particles.

Alpha Particles↗
PubMed1979

Cell survival following multiple-track alpha particle irradiation.

In experiments in which mammalian cells were irradiated with 5 . 6 MeV alpha particles from a Tandem Van de Graaff machine, we have confirmed the finding of others that the mean lethal dose (Do) is about 60 rad. However, on measuring the area of the nuclei of the flattened cells as they were irradiated, we found that this mean lethal dose corresponds to the passage of not one or two alpha particles per cell nucleus as expected but to between 10 and 20 particles. This allows for the possibility that the direct action of alpha particles on the nucleus may be the important event in carcinogenesis.

Alpha Particles↗
PubMed1989

Breakage of human interphase chromosomes by alpha particles and X-rays.

The technique of premature chromosome condensation (PCC) was used to compare the early formation of chromosome breaks in non-cycling HF19 human diploid fibroblasts when irradiated with slow alpha particles (3.2 MeV, 128 keV micron-1) or 250 kVP X-rays. For both radiations the production of PCC breaks increased approximately linearly with dose. The production coefficient for alpha particles was 12.5 +/- 0.6 per cent per Gy and for X-rays it was 5.8 +/- 0.2 per cell per Gy. Hence, the relative biological effectiveness (RBE) of the alpha particles was 2.16 +/- 0.13. This is smaller than reported values of the RBE for the production of chromosome-type exchange aberrations by slow alpha particles. This implies that there is a difference, spatial or qualitative, in the initial breaks produced by the densely ionizing alpha particle tracks and the more sparsely ionizing electron tracks from the X-rays.

Alpha Particles↗
PubMed1989

Alpha particle radio-immunotherapy: animal models and clinical prospects.

Short-lived isotopes that emit alpha particles have a number of physical characteristics which make them attractive candidates for radioimmunotherapy. Among these characteristics are high linear energy transfer and correspondingly high cytotoxicity; particle range limited to several cell diameters from the parent atom; low potential for repair of alpha-induced DNA damage; and low dependence on dose rate and oxygen enhancement effects. This report reviews the synthesis, testing and use in animal models of an alpha particle emitting radioimmunoconjugate constructed via the noncovalent chelation of Bismuth-212 to a monoclonal IgM antibody specific for the murine T cells/neuroectodermal surface antigen, Thy 1.2. These 212Bi-anti-Thy 1.2 immunoconjugates are capable of extraordinary cytotoxicity in vitro, requiring approximately three 212Bi-labeled conjugates per target cell to suppress 3H-thymidine incorporation to background levels. The antigen specificity afforded by the monoclonal antibody contributes a factor of approximately 40 to the radiotoxicity of the immunoconjugate. Animals inoculated with a Thy 1.2+ malignant ascites were cured of their tumor in an antigen-specific fashion by intraperitoneal doses of approximately 200 microCi per mouse. Alpha particle emitting radioimmunoconjugates show great potential for regional and intracavitary molecular radiotherapy.

Alpha Particles↗
PubMed1979

Transformation of mammalian cells by alpha particles.

Mammalian cells in culture have been shown here for the first time to be transformed by alpha irradiation. Mouse embryo (C3H 10T1/2) cells were transformed with 5.6 MeV alpha particles from a Tandem Van de Graaff machine. Malignant tumours were induced following inoculation of the transformed cells into syngeneic hosts. Unirradiated control cells failed to produce tumours. The morphology of the transformed foci was similar to that obtained by X-rays and chemicals but different from virally transformed cells. The transformation frequency increased approximately as the cube of the dose to a maximum of about 4 per cent ofthe surviving cells which occurred between 1.5 and 2.5 x 10(7) alpha particles per cm2 (205-342 rad). It appears that alpha particle irradiation may exert a direct effect on the genome of the cell to produce malignancy without any external immunological or hormonal influences.

Alpha Particles↗
PubMed1990

Alpha-particles induce preneoplastic transformation of rat tracheal epithelial cells in culture.

To characterize the potential role of high-l.e.t. radiation in respiratory carcinogenesis, the cytotoxic and transforming potency of 5.5 Me V alpha-particles from electroplated sources of 238Pu were determined using primary cultures of rat tracheal epithelial cells. The alpha-particle response was compared to the effects of 280 kVp X-rays and of the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine. Increasing the alpha-particle dose caused an exponential decrease in survival with a D37 of 1.6 Gy. X-rays also caused a dose-dependent decrease in survival (D37 = 3.6 Gy) but the survival curve had a significant shoulder. The RBE for cell killing by alpha-particles versus X-rays varied with dose, and ranged between 4 and 1.5 for alpha doses in the range 0.2-4 Gy. At equally toxic doses (relative survival 0.18-0.2), all three agents induced similar frequencies of preneoplastic transformation. For preneoplastic transformation induced by doses of alpha- and X-radiations giving 80 per cent toxicity, an alpha RBE of 2.4 was derived. The similar RBEs for cell killing and for preneoplastic transformation suggest an association between the type or degree of radiation-induced damage responsible for both cell killing and cell transformation.

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