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The combined effect of 532 nm laser radiation and alpha-particles on survival of Escherichia coli (AB 1157) has been investigated. The sensitivity of cells to alpha-particles was decreased by pre- and post-irradiation with laser.
The purpose of this study was to obtain information on the alpha-particle dose-response relationship of 244Cm in rats. Rats were exposed briefly by inhalation to graded levels of monodisperse aerosols of 244Cm2O3 heat-treated at 1150 degrees C. The initial lung burden (ILB) of each animal was determined by the use of the gamma-ray-emitting radionuclide 243Cm in the aerosols. Seven groups of 84-day-old F344/Crl rats (a total of 637 males and 645 females) were exposed once to 244Cm2O3 or sham-exposed to filtered ambient air. Mean ILBs of all rats per group ranged from 0.51 +/- 0.17 (+/-SD) to 240 +/- 82 kBq kg-1 body weight. Mean lifetime alpha-particle doses to the lungs per group ranged from 0.20 +/- 0.069 (+/-SD) to 36 +/- 6.5 Gy. After death, each rat was radiographed and necropsied. Dose-related increases occurred in incidences of benign and malignant lung neoplasms, except for the groups of rats with higher mean ILBs that were examined histologically (98 +/- 18 and 240 +/- 77 kBq kg-1 body weight) in which survival was markedly decreased. Also, average alpha-particle doses of 0.0014 +/- 0.00058 (+/-SD) to 0.17 +/- 0.091 Gy and 0.18 +/- 0.007 to 1.6 +/- 1.1 Gy were also absorbed by the liver and skeleton, respectively, in the rats in the different exposure groups. Primary liver neoplasms occurred in several rats. However, the incidence of these lesions was not related to dose. Increased incidences of bone neoplasms occurred only in rats receiving higher doses to the skeleton. Excess numbers of rats with lung neoplasms per 10(4) Gy to the lung per group ranged from 760 +/- 430 (+/- SE) at a mean dose of 0.48 Gy to 84 +/- 16 at a mean dose of 37 Gy. Risk factors for the lowest and highest ILB kg-1 body weight groups were not considered reliable because of large errors associated with these calculations and the life-span shortening in the highest ILB kg-1 group. Inhaled 244Cm2O3 appeared to be about 50% less effective as a lung carcinogen in rats compared to 239PuO2 at similar doses.
A model system has been used to test the efficacy of vascular targeting of alpha-particle emitter 213Bi for therapy of small, 'artificial' metastases in mouse lung. Specific monoclonal antibody (mAb) 201 B was used to deliver greater than 30% of the injected dose to lung where tumours had developed due to intravenous injection of cells. Specific 213Bi-mAb 201B treatment of BALB/c mammary carcinoma EMT-6 tumours in lung resulted in a dose-dependent destruction of tumours and an extended lifespan of treated animals relative to controls. Significant reduction of lung tumour burden was noted in animals treated with 0.93 MBq injected dose or as little as 14 Gy absorbed dose to the lung. Animals treated with higher doses (2.6-6.7 MBq) had nearly complete cure of lung tumours but eventually died of lung fibrosis induced by the treatment. Four other tumour cell types were studied: murine Line 1 lung carcinomas in syngeneic BALB/c mice, rat IC-12 tracheal carcinoma growing in severe combined immune deficient (SCID) mice, and two human tumours--epidermoid carcinoma A431 and lung carcinoma A549--growing in SCID mice. In all cases, the number of lung tumour colonies was reduced in animals treated with specific, labelled mAb relative to those in animals treated with control 213Bi MAb or EDTA complexed 213Bi. Tumours treated in immunodeficient SCID mice were partially destroyed or at least retarded in growth, but ultimately regrew and proved fatal, indicating that an intact immune function is necessary for complete cure. The data show that the short-lived alpha-particle emitter 213Bi can be effectively targeted to lung blood vessels and that tumour cells growing in the lung are killed. The mechanism may involve direct killing of tumour cells from alpha-particle irradiation, killing through destruction of blood supply to the tumour, or a combination of the two.
It is well accepted that cancer arises in a multistep fashion in which exposure to environmental carcinogens is a major etiological factor. The aim of this work was to establish an experimental breast cancer model in order to understand the mechanism of neoplastic transformation induced by high LET radiation in the presence of 17beta-estradiol (E). Immortalized human breast cells (MCF-10F) were exposed to low doses of high LET alpha particles (150 keV/microm) and subsequently cultured in the presence or absence of E for periods of up to 10 months post-irradiation. MCF-10F cells irradiated with either a single 60 cGy dose or 60/60 cGy doses of alpha particles showed gradual phenotypic changes including altered morphology, increase in cell proliferation relative to the control, anchorage-independent growth and invasive capability before becoming tumorigenic in nude mice. In alpha particle-irradiated cells and in those cells subsequently cultured in the presence of E, increased BRCA1, BRCA2 and RAD51 expression were detected by immunofluorescence staining and quantified by confocal microscopy. These studies showed that high LET radiation such as that emitted by radon progeny, in the presence of estrogen, induced a cascade of events indicative of cell transformation and tumorigenicity in human breast epithelial cells.
Alpha-particle spectrograms of bone samples from USTUR Case 246 were analyzed to determine the depth in tissue from which the 241Am alpha-particles were emitted. In four samples of bone, the lack of energy straggling in the alpha spectra indicated that essentially all the 241Am was deposited directly on the exposed bone surface, and none had been translocated to within bone volume. These findings agree well with the results of autoradiographic examination of bone samples from the same case, but are in marked contrast to findings on another case (USTUR Case 102) who had been exposed to a much smaller amount of 241Am at a younger age and survived approximately twice as long after the exposure. It is problematical whether the lack of 241Am redistribution, and therefore the implied absence of bone remodeling, in Case 246 was due to his advanced age at exposure or to a deterministic effect of alpha-irradiation on bone metabolism, but the observation of radiation effects on bone metabolism in former radium workers supports the latter.
Limited options for the treatment of prostate cancer have spurred the search for new therapies. One innovative approach is the use of targeted alpha therapy (TAT) to inhibit cancer growth, using an alpha particle emitting radioisotope such as (213)Bi. Because of its short range and high linear energy transfer (LET), alpha-particles may be particularly effective in the treatment of cancer, especially in inhibiting the development of metastatic tumors from micro-metastases. Prostate-specific membrane antigen (PSMA) is expressed in prostate cancer cells and the neovasculature of a wide variety of malignant neoplasms including lung, colon, breast and others, but not in normal vascular endothelium. The expression is further increased in higher-grade cancers, metastatic disease and hormone-refractory prostate cancer (PCA). J591 is one of several monoclonal antibodies (mabs) to the extracellular domain of PSMA. Chelation of J591 mab with (213)Bi forms the alpha-radioimmunoconjugate (AIC). The objective of this preclinical study was to design an injectable AIC to treat human prostate tumors growing subcutaneously in mice. The anti-proliferative effects of AIC against prostate cancer were tested in vitro using the MTS assay and in vivo with the nude mice model. Apoptosis was documented using terminal deoxynucleotidyl transferase [TdT]-mediated deoxyuridinetriphosphate [dUTP] nick end-labeling (TUNEL) assay, while proliferative index was assessed using the Ki-67 marker. We show that a very high density of PSMA is expressed in an androgen-dependent human PCA cell line (LNCaP-LN3) and in tumor xenografts from nude mice. We also demonstrate that the AIC extensively inhibits the growth of LN3 cells in vitro in a concentration-dependent fashion, causing the cells to undergo apoptosis. Our in vivo studies showed that a local AIC injection of 50 microCi at 2 days post-cell inoculation gave complete inhibition of tumor growth, whereas results for a non-specific AIC were similar to those for untreated mice. Further, after 1 and 3 weeks post-tumor appearance, a single (100 microCi/100 microl) intra-lesional injection of AIC can inhibit the growth of LN3 tumor xenografts (volume<100 mm(3)) in nude mice. Tumors treated with AIC decreased in volume from a mean 46+/-14 mm(3) in the first week or 71+/-15 mm(3) in the third week to non-palpable, while in control mice treated with a non-specific AIC using the same dose, tumor volume increased from 42 to 590 mm(3). There were no observed side effects of the treatment. Because of its in vitro cytotoxicity and these anti-proliferative properties in vivo, the (213)Bi-J591 conjugate has considerable potential as a new therapeutic agent for the treatment of prostate cancer.
The formulae for the RMS scattering angle given by small-angle multiple-scattering theory are discussed and a correction to the standard Rossi formula is derived. Values of the correction factor are calculated for protons, alpha-particles and heavy ions; these results show that the correction is important for protons and alpha-particles but negligible for heavy ions with mass number 12-40. The values of the RMS scattering angle and the RMS lateral displacement are calculated for a proton beam passing through water. For protons the correction for energy loss in thick targets is even more important.
Third-harmonic ion-cyclotron-resonance heating of 4He-beam ions has produced for the first time on the JET tokamak high-energy populations of 4He ions to simulate 3.5 MeV fusion-born alpha (alpha) particles. Acceleration of 4He ions to the MeV energy range is confirmed by gamma-ray emission from the nuclear reaction 9Be(alpha,ngamma) 12C and excitation of Alfvén eigenmodes. Concomitant electron heating and sawtooth stabilization are observed. The scheme could be used in next-step tokamaks to gain information on trapped alpha particles and to test alpha diagnostics in the early nonactivated phase of operation.
The technique of alpha spectrometry is used to detect alpha particles and to determine their energy. In this way the technique is able to provide simultaneously quantitative information (i.e. the activity) and qualitative information (the identity) on any radionuclide that emits an alpha particle. The longer-lived naturally occurring isotopes of thorium are all alpha emitters so the technique can be used to quantify them directly and this is extremely important if radiation doses due to intakes of these isotopes into the body are to be accurately assessed. The principle of the technique is discussed, its advantages and disadvantages, and the instrumentation that is commonly used today. The need for radiochemical separation is discussed and illustrated by reference to analysis procedures in current use for thorium isotopic analysis. Practical issues such as detection limits, quality control procedures. sample throughput and cost will be covered.
A method is described which allows dose calculations to be made to individual target cells in different regions of mouse bone marrow exposed to alpha particles emitted from bone. The method takes into account the variable rate of transfer of energy along the tracks of alpha particles and was applied to experiment-based values calculated for the concentration of 224Ra on bone surfaces after an injection of a leukemogenic amount of the nuclide. These calculations show a minimum dose of 11 Gy in small (less than 50-micron) marrow spaces and 10 Gy close to bone surface in the shaft of the femur. The results suggest that leukemogenic doses are likely to occur at some distance from bone surfaces in wide marrow spaces and that osteosarcoma is not likely to be induced directly in cells immediately aligning bone surfaces.
A study was made of the postirradiation recovery of yeast Pichia pinus exposed to gamma-quanta and alpha-particles. No recovery was noted in the haploid cells: the nonreversible component k = 1. In the diploid cells, the nonreversible component k = 0.7 and k = 0.8 after exposure to gamma-quanta and alpha-particles, respectively.
The rate of cellular losses of hypoxic respectively euoxic cells of the solid experimental tumor "sarcoma 180" was examined in vivo after irradiations with gamma rays, 15 MeV neutrons, and alpha particles. The tumor cells were labeled in vivo, at first with 125I-UdR and after 50 hours with 131I-UdR. After a further interval of about 20 hours the tumor was irradiated. This method of double labeling makes it possible to determine externally the rates of cellular losses in the labeled zones of tumor cells presenting different partial oxygen pressures. The increase of the rates of cellular losses among the euoxic and hypoxic tumor cells induced by the gamma radiation differs by 2.6; it decreases, however, to 1.5 after injection of nitrofurazone prior to the irradiation. After irradiation with 15 MeV neutrons, a difference of only 1.4 was observed. If the tumors were irradiated internally with alpha particles from the reaction 10B(n,alpha) 7Li, there was no difference between the two rates of cellular losses. As far as the above mentioned kinds of radiation are concerned, the ratios from the increase of the rates of cellular losses induced by radiation are well corresponding to the oxygen enhancement found by other authors during their examinations in vitro.
It is reported that thoron concentration in Japanese dwellings may be higher than in other dwellings. Therefore, in order to assess the risk for indoor thoron progeny, the portable potential alpha-energy monitor has been developed. The monitor detects alpha-particles from the 212Po collected on the filter using a piece of cellulose nitrate film. The detection efficiency of the alpha-particles has been estimated by Monte Carlo calculation. From the results of measurements, the mean indoor thoron progeny concentration in the dwellings was 1.5 Bq m-3 (ECTn), and ranged from 0.04 to 8.2 Bq m-3. The effects of three typical interior walls (soil-based plaster, concrete, and modern materials) on the thoron progeny supply were considered. The mean annual effective dose equivalent was 0.45 mSv.
Breeding performances are compared of hybrid female mice given 239Pu (5 or 10 mu Cikg-1 body mass in 1% trisodium citrate via the tail-vein), or kept in a 10 rad/day or 20 rad/day 60Co gamma-irradiation field (but mated in the control area), or unirradiated. Ovarian dose-rates from the injected plutonium were initially 0.8 and 1.7 rad/day, changing little thereafter; actual gamma-ray dose-rates to breeding females averaged around 8 and 16 rad/day respectively. Both gamma-ray treatments affected reproductive performance more than the plutonium injections, with respet to duration of fertility and to offspring per litter in successive 4-weekly periods, though overall mean litter-sizes were not significantly less than controls. The r.b.e. for these effects on reproduction, attributed to germ-cell killing, is about 2.5 for the alpha-particles vs. gamma-rays, lower than for testis mass reduction in males. This low r.b.e. may be connected with inhomogeneity of alpha-particle dose within the ovary, but it is known that fission neutron versus gamma r.b.e.'s for impairment of female fertility are also lower than those for impairment of male fertility.
Two conflicting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive AL cell mutagenic assay, we show here that non-irradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a single alpha particle each. Pretreatment of cells with a low dose of X-rays four hours before alpha particle irradiation significantly decreased this bystander mutagenic response. Results from the present study address some of the fundamental issues regarding both the actual target and radiation dose effect and can contribute to our current understanding in radiation risk assessment.
A silicon semiconductor photodiode was used to measure the TL-signal of TLD-300 (CaF2:Tm) detectors irradiated with 60Co gamma rays and 226Ra alpha particles. The applied dose values varied from 0.12 to 14.3 Gy for gamma rays and from about 50 to 300 Gy for alpha particles. Because of the infrared sensitivity of the photodiode the infrared emission of the planchet and the TLD-detector produced a high output signal above about 200 degrees C. In addition to this background signal an infrared emission from the TLD-300 detectors could be detected. This infrared TL-signal exhibited the same dose dependences as the visible signal, but the amplitude was higher than that of the visible TL-signal. For the applied photodiode the ratio of the infrared TL-signal to the visible TL-signal was about 24 for the 100 degrees C peak, about 15 for the 150 degrees C peak and 6 for the 240 degrees C peak.
High linear energy transfer radioisotopes carried by appropriate agents have been proposed for receptor-directed radiotherapy. Two such classes of isotopes are Auger electron and alpha-emitting nuclides. To determine the relative cytotoxicity and nuclear damage to cells produced by these two classes of nuclides, we compared bromine-80m (80mBr), an Auger-electron-emitting radionuclide with a 4.4-hour half-life, with bismuth-212 (212Bi), an alpha-emitter with a 1-hour half-life. Because of the short path length of the Auger electrons, 80mBr was radiotoxic only when incorporated into DNA, such as in the form of [80mBr]bromodeoxyuridine ([80mBr]BrUdR). Both agents induced linear increases in chromosome aberration frequency, however, [80mBr]BrUdR caused multiple aberrations including the shattering of parts of the chromosomes. While, in contrast, a 2-hour exposure of cells to 212Bi, chelated to DTPA, a form which does not enter the cell, induced much less extensive chromosome damage. Exposure to equivalent activities of Auger electrons or alpha-particles results in 5 times more damage in Auger-electron-exposed cells. However, estimates of dose suggest they are equally toxic. Unlike Auger electrons, alpha-particles did not need to be in as close proximity to the DNA to have clastogenic and radiotoxic effects.
Eyeglass lenses are commonly composed of allyl-diglycol carbonate (CR-39), an alpha-particle detecting plastic, thus making such lenses personal radon dosimeters. Samples of such lenses have been etched to reveal that radon and radon progeny alpha tracks can be seen in abundance, and sensitivities have been calibrated in radon chambers as a primary calibration and with a uranium-based source of alpha particles as a convenient secondary standard. Natural, environmental (fossil) track densities ranged from 3,000 to 25,000 cm(-2) for eyeglasses that had been worn for various times from 1 to nearly 5 y. Average radon concentrations to which the wearers were exposed are inferred to be in the range 20 to 130 Bq m(-3) (0.5 to 3.5 pCi L(-1)). Procedures for consistent, meaningful readout are described.