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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↗
PubMed1984

Experimental examination of cavity ionisation theory applied to alpha-particle fields.

The form of a general theory of cavity ionisation is outlined and its applications to alpha-particle fields considered. The attenuation of the alpha particles within the cavity, which gives rise to the weighting factor in general cavity theory, is considered in detail and an appropriate treatment for alpha-particle fields developed. Apparatus, consisting of an ionisation chamber composed of electrodes emitting alpha rays, was constructed in order to impose a rigorous test on the theory in the most critical region of cavity size. The general theory of cavity ionisation as applied to alpha-particle fields is shown to be in close agreement with the experimental results. As in the case of photon and electron fields, it is possible to characterise a cavity by a single chord length (path length) but the charged particle energy spectrum and the variation of stopping power with energy must be considered in detail.

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↗
PubMed1994

Alpha particles are extremely damaging to developing hemopoiesis compared to gamma irradiation.

Estimates of risk of stochastic effects from contamination with alpha-particle-emitting radionuclides are based on equivalent doses which take into account the RBE of the high-LET radiation. ICRP has recommended a dose-weighting factor, wR, of 20 for alpha-particle radiation. It is assumed that the RBEs for deterministic effects are considerably less than those for stochastic effects. However, the offspring of mice injected with 30 Bq g-1 239Pu at 13 days gestation develop a persistent deficit in hemopoietic stem cells which is primarily the result of damage to their regulatory microenvironment. Their spatial distribution in the marrow is also perturbed, and recent observations on those mice suggested a considerably higher factor than 20. To define a more realistic RBE for hemopoiesis, the effects of external gamma irradiation during the fetal development period have been compared directly with those of 239Pu incorporated via placental transfer on the development of hemopoietic tissue. Pregnant mice were irradiated with 60Co gamma rays (a) continuously from day 13 of gestation to birth at 0.15 or 0.6 Gy/day; (b) six repeated acute doses (0.6 Gy/min) at 0.1 or 0.3 Gy from day 13 of gestation; (c) one acute dose of 0.6 or 1.8 Gy on day 15 of gestation. The spatial distribution of hemopoietic stem cells in 8-week-old offspring was then determined and compared to that resulting from alpha-particle irradiation. In each case, the higher dose was required to match the results for alpha particles, suggesting an RBE for developing hemopoiesis of 250-360 compared to a continuous gamma-ray dose and a rather lower value of 130-180 compared to a single acute dose of gamma rays. This contrasts greatly to values for direct irradiation of the stem cells but argues that the effective RBE, measured for long-term effects in vivo, is the more realistic. It is concluded that an all-embracing factor can be grossly misleading in the specification of protection guidelines and can greatly underestimate the risks of exposure to alpha particles.

Alpha Particles↗
PubMed1994

Neoplastic transformation dose response of oncogene-transfected rat embryo cells by gamma rays or 6 MeV alpha particles.

We measured a dose-response relationship for induction of neoplastic transformation by 6 MeV alpha particles and 137Cs gamma rays in REC:myc and REC:ras cells, that is, rat embryo cells (REC) transfected with the c-myc or the Ha-ras oncogenes. The 6 MeV alpha particles simulated 222Rn emissions for risk assessment relative to low-LET radiations. The dose of gamma rays was approximately twice that of alpha particles for a neoplastic transformation frequency of 10(-3). The survival of the REC cells containing oncogenes was comparable to that of the commonly used C3H 10T1/2 cells for the same dose, but the former were more refractory to radiation-induced neoplastic transformation. Neoplastic transformation frequency measured in REC cells was 3 times lower than those typically measured in C3H 10T1/2 cells at a gamma-ray dose of 6 Gy, and 5-10 times lower at an alpha-particle dose of 3 Gy.

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↗
PubMed1994

TASTRAK spectroscopy of polonium-210 alpha-particle activity at bone surfaces: evidence for a concentrated surface deposit less than 3 microns deep.

The technique of alpha-particle spectroscopy by CR-39 type TASTRAK plastic has been used to study the depth distribution of natural alpha-particle emitters at the surface of human bone. The predominant component of this alpha-particle activity was 210Po supported by 210Pb, although a smaller activity of 226Ra was also detected. Autopsy samples of human femur and cranium were obtained from subjects age 63 to 86. Both cortical and trabecular surfaces were analyzed. The results indicate that 210Pb-supported 210Po is concentrated at the surfaces of human bone from elderly subjects, in a narrow band 3 microns deep or less, by a factor of about four. As a result, the alpha-particle dose to the nuclei of cells lining bone surfaces is around 1.8 times greater than that calculated for a uniform volume distribution. Polonium-210 activity indicates the distribution of 210Pb, and of stable lead, received by continuous intake throughout life at a very low level. A persistent bone surface concentration of lead and other osteotropic metals may be associated with the hypermineralized layer about 1 micron thick which occurs at the surface of resting bone mineral.

Aged↗
PubMed1984

The genotoxicity of alpha particles in human embryonic skin fibroblasts.

Cell inactivation and induced mutation frequencies at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus have been measured in cultured human fibroblasts (GM10) exposed to alpha particles from 238Pu (LET at the cell surface was 100 keV/microns) and 250 kVp X rays. The survival curves resulting from exposure to alpha particles are exponential. The mean lethal dose, D0, is approximately 1.3 Gy for X rays and 0.25 Gy for alpha particles. As a function of radiation dose, mutation induction at the HGPRT locus was linear for alpha particles whereas the X-ray-induced mutation data were better fitted by a quadratic function. When mutation frequencies were plotted against the log of survival, mutation frequency at a given survival level was greater in cells exposed to alpha particles than to X rays.

Alpha Particles↗
PubMed1995

Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells.

We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha Particles↗
PubMed1987

Absence of a dose-rate effect in the transformation of C3H 10T1/2 cells by alpha-particles.

The findings of Hill et al. (1984) on the greatly enhanced transformation frequencies at very low dose rates of fission neutrons induced us to perform an analogous study with alpha-particles at comparable dose rates. Transformation frequencies were determined with gamma-rays at high dose rate (0.5 Gy/min), and with alpha-particles at high (0.2 Gy/min) and at low dose rates (0.83-2.5 mGy/min) in the C3H 10T1/2 cell system. alpha-particles were substantially more effective than gamma-rays, both for cell inactivation and for neoplastic transformation at high and low dose rates. The relative biological effectiveness (RBE) for cell inactivation and for neoplastic transformation was of similar magnitude, and ranged from about 3 at an alpha-particle dose of 2 Gy to values of the order of 10 at 0.25 Gy. In contrast to the experiments of Hill et al. (1984) with fission neutrons, no increased transformation frequencies were observed when the alpha-particle dose was protracted over several hours.

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↗
PubMed1984

Cell cycle dependent G2 delay and killing of L929 cells after exposure to 241Am alpha particles.

Survival and G2 delay of L929 mouse fibroblasts exposed to 3.4-MeV alpha particles depend on the cell age at the time of irradiation. Greatest sensitivity for both endpoints has been found at the G1/S transition: The surviving fraction of G1/S cells is reduced to 0.11 following 1 Gy of alpha particles compared to 0.31 for early G1 cells. The G2 + M transit time rises from 3 hr for control cells to 22 and 30 hr for cells irradiated with 0.3 Gy in G2 or at the G1/S boundary, respectively. Cells irradiated in early G1 do not show increased G2 + M transit times. Growth delay as calculated for the entire population increases linearly with dose by 23 hr/Gy of alpha particles.

Alpha Particles↗
PubMed1987

The effect of 238Pu alpha-particles on the mouse fibroblast cell line C3H 10T1/2: characterization of source and RBE for cell survival.

Considerable interest has been aroused in recent years by reports that the transforming and carcinogenic effectiveness of low doses of high LET radiations can be increased by reducing the dose rate, especially for transformation of 10T1/2 cells in vitro by fission-spectrum neutrons. We report on conditions which have been established for irradiation of 10T1/2 cells with high LET monoenergetic alpha-particles (energy of 3.2 MeV, LET of 124 keV microns-1) from 238Pu. The alpha-particle irradiator allows convenient irradiation of multiple dishes of cells at selectable high or low dose rates and temperatures. The survival curves of irradiated cells showed that the mean lethal dose of alpha-particles was 0.6 Gy and corresponded to an RBE, at high dose rates, of 7.9 at 80 per cent survival and 4.6 at 5 per cent survival, relative to 60Co gamma-rays. The mean areas of the 10T1/2 nuclei, perpendicular to the incident alpha-particles, was measured as 201 microns2, from which it follows that, on average, only one in six of the alpha-particle traversals through a cell nucleus is lethal. Under the well-characterized conditions of these experiments the event frequency of alpha-particle traversals through cell nuclei is 9.8 Gy-1.

Alpha Particles↗
PubMed1994

Relative biological effectiveness of alpha-particle emitters in vivo at low doses.

The therapeutic potential of radionuclides that emit alpha particles, as well as their associated health hazards, have attracted considerable attention. The 224Ra daughters 212Pb and 212Bi, by virtue of their radiation properties which involve emission of alpha and beta particles in their decay to stable 208Pb, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of 212Pb and its daughters. When 212Pb, in equilibrium with its daughters 212Bi, 212Po and 208Tl, was administered directly into the testis, the dose required to achieve 37% survival (D37) was 0.143 +/- 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the D37 for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210Po, was used to obtain an RBE-LET relationship for alpha particles emitted by tissue-incorporated radionuclides: RBE alpha = 4.8 - 6.1 x 10(-2) LET + 1.0 x 10(-3) LET2. Similarly, the dependence of RBE on alpha-particle energy E alpha was given by RBE alpha = 22 E(-0.73) alpha. These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of alpha-particle emitters.

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↗