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PubMed1994

Vitamins as radioprotectors in vivo. I. Protection by vitamin C against internal radionuclides in mouse testes: implications to the mechanism of damage caused by the Auger effect.

The potential of vitamin C, an antioxidant, to protect the radiosensitive spermatogonial cells in mouse testes against the effects of chronic irradiation by radionuclides incorporated into tissue was investigated. Interestingly, when injected intratesticularly, a small and nontoxic amount of vitamin C (1.5 microgram in 3 microliters saline) protected the spermatogonia against the damage associated with high-LET radiation caused by Auger electrons from similarly administered 5-(125I)-iodo-2'-deoxyuridine (125IdU). A dose modification factor (DMF) of 2.3 was obtained. In contrast, no protection was observed when 210Po, an alpha-particle emitter, was administered similarly. These findings suggest that the mechanism of action of the Auger effect is of an indirect nature, which is in contrast to the direct action generally believed to be responsible for biological damage caused by high-LET radiations.

Alpha Particles↗

PubMed1986

[Irradiation of grades III and IV astrocytomas with new types of radiation].

Until 1983, more than 300 astrocytomas of degree III and IV have been irradiated all over the world with new types of radiation such as neutrons, protons, alpha particles, heavy ions, and pions. Up to now a therapeutic progress could not be achieved. Radiobiologic experimentations suggest that the dense ionisation is unfavorable in the irradiation of malignant cerebral tumors. The clinical radiotherapy research with protons should therefore be intensified and hyperfractionation should be critically reviewed.

Alpha Particles↗

PubMed1995

Estimates of radiogenic cancer risks.

A methodology recently developed by the U.S. EPA for estimating the carcinogenic risks from ionizing radiation is described. For most cancer sites, the risk model is one in which age-specific, relative risk coefficients are obtained by taking a geometric mean of the coefficients derived from the atomic bomb survivor data using two different methods for transporting risks from the Japanese to the U.S. population. The risk models are applied to estimate organ-specific risks per unit dose for a stationary population with mortality rates governed by 1980 U.S. vital statistics. With the exception of breast cancer, low-LET radiogenic cancer risk estimates are reduced by a factor of 2 at low doses and dose rates compared to acute high dose exposure conditions. For low dose (or dose rate) conditions, the risk of inducing a premature cancer death from uniform, whole body, low-LET irradiation is calculated to be 5.1 x 10(-2) Gy-1. Neglecting nonfatal skin cancers, the corresponding incidence risk is 7.6 x 10(-2) Gy-1. High-LET (alpha particle) risks are presumed to increase linearly with dose and to be independent of dose rate. High-LET risks are estimated to be 20 times the low-LET risks estimated under low dose rate conditions, except for leukemia and breast cancer where RBEs of 1 and 10 are adopted, respectively.

Adolescent↗

PubMed2000

Dose- and time-response relationships for lethal mutations and chromosomal instability induced by ionizing radiation in an immortalized human keratinocyte cell line.

PURPOSE: To investigate the relationship between two well-established delayed effects of ionizing radiation, experiments were conducted to determine the induction and expression of lethal mutations (delayed reproductive death) and chromosomal instability with respect to dose and time in a human immortalized keratinocyte cell line. METHODS: HPV-G cells were gamma- or alpha-irradiated and maintained in culture for up to 72 population doublings. At intervals, measurements were made of cloning efficiency and the cells examined for apoptosis and cytogenetic aberrations. RESULTS: The descendants of cells surviving 1 or 3 Gy gamma-irradiation, but not 0.5 Gy gamma-irradiation, exhibited a reduced colony-forming efficiency. The reduction persisted at a constant rate of 15-20% clonogenic cell loss per population doubling for up to 72 population doublings. Apoptosis was demonstrated in all colonies in the 1 and 3 Gy groups at 30 and 72 population doublings post-irradiation but not in the 0.5 Gy group. A significant persistent reduction in colony-forming ability (approximately 80%) was demonstrated in the progeny of cells irradiated with 0.5 Gy alpha-particles. After 30 population doublings, the proportion of chromosomally aberrant cells was significantly greater than control values for all doses of both high- and low-LET radiations. The major cytogenetic aberrations (chromatid breaks, chromosome fragments and minutes) were consistent with the transmission of chromosomal instability. The expression of instability declined between 30 and 72 population doublings in the 0.5 Gy and 3 Gy gamma-irradiation groups, but persisted up to 72 population doublings in the 1 Gy group. The expression of chromosomal instability was greater in the descendants of alpha-irradiated cells and showed little evidence of reduction with time. CONCLUSIONS: Unstable aberrations characteristic of radiation-induced chromosomal instability may commonly result in apoptosis and account for a component of the delayed reproductive death/lethal mutation phenotype in HPV-G cells. However, the absence of lethal mutations in the descendants of 0.5 Gy gamma-irradiated cells indicates a low-LET threshold effect for this particular endpoint. Overall, and particularly at low doses, there is no direct correlation between the two endpoints, indicating the absence of a simple relationship between these manifestations of radiation-induced genomic instability.

Alpha Particles↗

PubMed1985

Use of computer memory chips as the basis for a digital albedo neutron dosimeter.

We have measured the sensitivity of commercially available dynamic random access memories (D-RAMs) to alpha particles. Using a beam of 14-meV neutrons and a 6LiF crystal as a converter we have measured sensitivities to neutron radiation as high as 9.25 memory errors per millirem. We estimate that an optimized converter would produce even higher sensitivities as an albedo dosimeter in realistic radiation fields. Such a device would have a number of operational advantages.

Alpha Particles↗

PubMed2006

Alpha-radioimmunotherapy of intraperitoneally growing OVCAR-3 tumors of variable dimensions: Outcome related to measured tumor size and mean absorbed dose.

UNLABELLED: The purpose of this work was to (a) investigate the efficacy of radioimmunotherapy using 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 (nonspecific antibody) against differently advanced ovarian cancer in mice; (b) image the tumor growth on the peritoneum; and (c) calculate the specific energy and mean absorbed dose to tumors and critical organs. METHODS: Two experiments with 5-wk-old nude mice (n = 100 + 93), intraperitoneally inoculated with approximately 1 x 10(7) NIH:OVCAR-3 cells, were done. At either 1, 3, 4, 5, or 7 wk after inoculation animals were intraperitoneally treated with approximately 400 kBq 211At-MX35 F(ab')2 (n = 50 + 45), approximately 400 kBq 211At-Rituximab F(ab')2 (n = 25 + 24), or unlabeled Rituximab F(ab')2 (n = 25 + 24). At the time of treatment 29 animals were sacrificed and biopsies were taken for determination of tumor sizes using scanning electron microscopy (SEM). Eight weeks after each treatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. The specific energy and mean absorbed dose to tumors were calculated. The activity concentration was measured in critical organs and abdominal fluid. RESULTS: When given treatment 1, 3, 4, 5, or 7 wk after cell inoculation the tumor-free fraction (TFF) was 95%, 68%, 58%, 47%, 26%, and 100%, 80%, 20%, 20%, and 0% when treated with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2, respectively. The SEM images revealed maximum tumor radius of approximately 30 mum 1 wk after cell inoculation, increasing to approximately 340 mum at 7 wk. Specific energy to cell nuclei varied between 0 and approximately 540 Gy, depending on assumptions regarding activity distribution and tumor size. The mean absorbed dose to thyroid, kidneys, and bone marrow was approximately 35, approximately 4, and approximately 0.3 Gy, respectively. CONCLUSION: Treatment with 211At-MX35 F(ab')2 or 211At-Rituximab F(ab')2 resulted in a TFF of 95%-100% when the tumor radius was < or =30 microm. The TFF was decreased (TFF < or = 20%) for 211At-Rituximab F(ab')2 when the tumor radius exceeded the range of the alpha-particles. The specific antibody gave for these tumor sizes a significantly better TFF, explained by a high mean absorbed dose (>22 Gy) from the activity bound to the tumor surface and probably some contribution from penetrating activity.

Alpha Particles↗

PubMed2005

A simple method for measuring thoron spatial distributions.

A simple but effective method that allows the measurement of the 220Rn spatial distribution in working or living environments using a solid-state detector is presented in this paper. The method is based on measurements of the alpha particles emitted by 216Po (the first 220Rn progeny) directly deposited on the detector surface at different distances from a 220Rn exhalation source. The validity of the method is shown by comparing the results of an experiment, where the 220Rn activity concentration is measured under conditions of diffusion at constant temperature, with finite-element calculations.

Air Pollution, Indoor↗

PubMed1993

Track studies in water vapor using a low-pressure cloud chamber. II. Microdosimetric measurements.

A low-pressure cloud chamber has been adapted to operate with pure water vapor. Photographs were obtained of tracks arising from the passage of ionizing radiation. The sources used were low-energy X rays, 242Cm alpha particles, and low-energy protons. Distributions of lineal energy, radial distances around an ion track, and interdroplet distances were measured and compared with the predictions of Monte Carlo calculations. After allowing for diffusion and the limitations of the geometry of the system, the measured and calculated distributions were found to be in good agreement.

Alpha Particles↗

PubMed1985

Plutonium in gonads: a summary of the current status.

A review of the literature was carried out to investigate the following: the fraction of Pu in the body that was in the gonads; the necessity for a localization factor in calculating the genetic dose to humans; and the possibility that an unexpectedly high relative biological effectiveness (RBE) causing genetic effects could occur for alpha particles. Human autopsy data from both occupationally exposed persons and the public were relied on to determine the amount of Pu in the gonads. It was found that an average fraction of 3 X 10(-3) of the Pu in the body was in the ovaries and testes but there was a wide variation among individuals. While a localization factor over the average of 2.5-4 is needed to calculate the dose to the sensitive cells for rodents, no such factor is required for the human. Information on the RBE for various genetic effects shows RBEs for Pu alpha's about as would be expected from neutron irradiation. The usual quality factor applied in calculating dose equivalent is appropriate and may be conservative, particularly for females.

Alpha Particles↗

PubMed1984

A multidetector alpha spectroscopy analysis system.

This document describes the attributes of an alpha spectroscopy counting and analysis system called Low Level Pulse Height Analysis (LLPHA). It was developed for multi-sample alpha spectroscopy analysis. The LLPHA system is controlled by a MIK-11/2 microcomputer with 28K of memory and uses a double-density, dual floppy disk for data storage. Detectors are interfaced to the computer via CAMAC (Computer Automated Measurement and Control) equipment. The system simultaneously supports 32 active and independent surface-barrier alpha-particle detectors. It operates with the total collection rate of up to 300 counts/sec from all active detectors, using 128 channels per spectrum and a dynamic energy range of 1.4 MeV. The system is not limited, however, to these conditions. In addition to spectral acquisition, the system provides analysis functions which include peak identification, curve-smoothing, integration, linear and logarithmic scale graphics, and corrections for base-line shift, dead-time, and background counts. These functions can be implemented while other spectra are being collected. The LLPHA system represents a highly cost-effective means of acquiring alpha spectrometric data from a large number of samples simultaneously and with rapid data analysis capability.

Alpha Particles↗

PubMed1993

Contributions of nuclear medicine to the therapy of malignant tumors.

Radionuclides are applied in oncology for diagnosis and therapy. The former demands gamma--emitting radionuclides for labeling specific substrates for localizing malignant tissue and for analyzing tumor metabolism in vivo. Here, positron emission tomography (PET) may register in vivo the metabolism, for example, of glucose, amino acids, and receptors and of potentially useful cytotoxic agents. The advantage of the positron emitting radionuclides of carbon, nitrogen and fluorine is the labeling of substrates without changing substrate specificity within the metabolic reaction chain; also, substrate concentration in situ may be quantified. With regard to therapy radionuclides that emit beta- and alpha-particles or decay by electron capture with the Auger effect, are administered in ionic form or with tumor seeking substrates. Examples are radioiodine for treating thyroid malignancy and radiophosphorus for myeloproliferative diseases. Organically bound radionuclides are given as labeled ligands for specific receptors, such as meta-iodo-benzylguanidine (MIBG) for treating the catecholamine producing tumors phaeochromocytoma and neuroblastoma and labeled monoclonal antibodies for tumors specific receptors. Highly localized energy depositions come from Auger emitters such as 125I and by the neutron capture therapy, where boron-10 in the tumor cell is exposed to thermal neutrons for initiating the B10 (n; alpha) Li7 reaction, especially for treating neuro- and glioblastoma and melanoma. Endogenous radiotherapy with radionuclides rely on the success of delivering a proper amount of energy into individual tumor cells with optimal protection of normal tissue. The inevitable heterogeneity of energy deposition events from such approaches demands careful dosimetric assessment for which the classical methods of dosimetry for percutaneous radiotherapy are not applicable.

Alpha Particles↗

PubMed2004

Biological responses in known bystander cells relative to known microbeam-irradiated cells.

Normal human fibroblasts in plateau phase ( congruent with 95% G(1) phase) were stained with the vital nuclear dye Hoechst 33342 (blue fluorescence) or the vital cytoplasmic dye Cell Tracker Orange (orange fluorescence) and plated at a ratio of 1:1. Only the blue-fluorescing nuclei were microbeam-irradiated with a defined number of 90 keV/microm alpha particles. The orange-fluorescing cells were then "bystanders", i.e. not themselves hit but adjacent to cells that were. Hit cells showed a fluence-dependent induction of micronuclei as well as delays in progression from G(1) to S phase. Known bystander cells also showed enhanced frequencies of micronuclei (intermediate between those seen in irradiated and control cells) and transient cell cycle delays. However, the induction of micronuclei in bystander cells did not appear to be dependent on the fluence of the particles delivered to the neighboring hit cells. These are the first studies in which the bystander effect has been visualized directly rather than inferred. They indicate that the phenomenon has a quantitative basis and imply that the target for radiation effects cannot be considered to be the individual cell.

Alpha Particles↗

PubMed2003

The bystander effect.

The bystander effect refers to the induction of biological effects in cells that are not directly traversed by a charged particle. The data available concerning the bystander effect fall into two quite separate categories, and it is not certain that the two groups of experiments are addressing the same phenomenon. First, there are experiments involving the transfer of medium from irradiated cells, which results in a biological effect in unirradiated cells. Second, there is the use of sophisticated single particle microbeams, which allow specific cells to be irradiated and biological effects studied in their neighbors; in this case communication is by gap junction. Medium transfer experiments have shown a bystander effect for cell lethality, chromosomal aberrations and cell cycle delay. The type of cell, epithelial vs. fibroblast, appears to be important. Experiments suggest that the effect is due to a molecule secreted by irradiated cells, which is capable of transferring damage to distant cells. Use of a single microbeam has allowed the demonstration of a bystander effect for chromosomal aberrations, cell lethality, mutation, and oncogenic transformation. When cells are in close contact, allowing gap junction communication, the bystander effect is a much larger magnitude than the phenomenon demonstrated in medium transfer experiments. A bystander effect has been demonstrated for both high- and low-LET radiations but it is usually larger for densely ionizing radiation such as alpha particles. Experiments have not yet been devised to demonstrate a comparable bystander effect on a three-dimensional normal tissue. Bystander studies imply that the target for the biological effects of radiation is larger than the cell and this could make a simple linear extrapolation of radiation risks from high to low doses of questionable validity.

Alpha Particles↗

PubMed2001

Concerning the low uranium and thorium yields in the electrodeposition process of soil and sediment analyses.

The very low yields obtained in a common method of alpha-particle spectrometry for the determination of uranium and thorium in soil and sediment samples of environmental origin were investigated. Several experiments were performed to determine the cause. The results suggest that aluminium may cause major chemical interference in the electrodeposition process, and can be considered to be primarily responsible for the low recoveries found. A procedure is proposed to resolve this problem.

Alpha Particles↗

PubMedDate not supplied

Standardization of 125I and 238Pu.

A simple distance-variable detection table on which two detectors can be mounted and moved back and forth facing each other centred on a sample source has been constructed for photon-photon and alpha-photon coincidence counting for 125I and 238Pu, respectively. Two NaI(Tl) detectors were used for the standardization of 125I. A Si detector and an NaI(Tl) detector were employed for the standardization of 238Pu. The NaI(Tl) detectors have a very thin aluminium window for measuring low-energy photons from 125I and 238Pu while the Si-detector is a usable-in-air ion-implanted detector for alpha particles from 238Pu. A thin collodion film was used for 238Pu samples, whereas a thick polyester film was used for 125I samples to prevent 125I from leaking from the sample. The key comparison result of 125I showed good agreement, and the result of 238Pu was also compared with that of liquid scintillation counting.

Algorithms↗

PubMed1987

Radial dose distribution for 18.3 MeV/n alpha beams in tissue-equivalent gas.

Experimental measurements of the radial restricted linear energy transfer (LETr) for alpha beams of 18.3 MeV/n in tissue-equivalent gas were presented. The radial dose distribution for the alpha beam was deduced from the restricted LET measurements. A differential W value for the alpha particle in the tissue-equivalent gas was also deduced. The result for the differential W value was 29.0 +/- 0.9 eV/ion pair. The radial dose varied according to an inverse-square function with distance from the track center for radii larger than 0.026 micron. The maximum extension of the track, the penumbra radius, as 2.73 +/- 1.67 microns, which was less than predicted by calculations (7-9 microns).

Alpha Particles↗

PubMed1994

Radiation-induced chromosomal aberrations in mouse 10T1/2 cells: dependence on the cell-cycle stage at the time of irradiation.

Cell-cycle stage radiosensitivity for the induction of chromosome aberrations has been investigated in C3H 10T1/2 cells. Exponentially growing cells were irradiated with 3 Gy X-rays (80 kVp) or 0.6 Gy alpha-particles (LET = 101 keV/micron). The two doses produce the same survival level (37%) in the asynchronous population. Cells were harvested at four different times following irradiation and cell-cycle phase at the time of irradiation was assessed by using the differential replication staining technique. The frequency of chromosome aberrations produced in a given stage of the cell cycle was not constant as a function of the sampling time, but this could not be simply related to the existence of subphases exhibiting different radiosensitivity, because of cell-cycle perturbation introduced by radiation. X-radiation induced more exchanges than deletions, whereas a predominance of isochromatid deletions was observed after alpha-irradiation. This can be interpreted on the basis of the different patterns of energy deposition of densely- and sparsely-ionizing radiation. Both X- and alpha-rays produced a significant increase in the frequency of Robertsonian translocations when cells were exposed in G1 or S phase, but not in G2 phase.

Alpha Particles↗

PubMed1996

Cellular and molecular alterations in human epithelial cells transformed by high LET radiation.

An understanding of the radiobiological effects of high LET radiation is essential for human risk estimation and radiation protection. In the present study, we show that a single, 30 cGy dose of 150 keV/micrometer 4He ions can malignantly transform human papillomavirus immortalized human bronchial epithelial [BEP2D] cells. Transformed cells produce progressively growing tumors in nude mice. The transformation frequency by the single dose of alpha particles is estimated to be approximately 4 X 10(-7). Based on the average cross-sectional area of BEP2D cells, it can be calculated that a mean traversal of 1.4 particles per cell is sufficient to induce tumorigenic conversion of these cells 3 to 4 months post-irradiation. Tumorigenic BEP2D cells overexpress mutated p53 tumor suppressor oncoproteins in addition to the cell cycle control gene cyclin D1 and D2. This model provides an opportunity to study the cellular and molecular changes at the various stages in radiation carcinogenesis involving human cells.

Alpha Particles↗