Epithelial lesions induced by alpha particles and cigarette smoke condensates in organotypic culture of human bronchus.
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A shuttle vector, pZ189, carrying a bacterial suppressor tRNA marker gene (supF) was dissolved in Tris-EDTA buffer containing 0.3 M 10B-enriched boric acid and then irradiated with boron neutron captured beam (BNCB) produced by the nuclear reaction 10B (n,alpha) 7Li with thermal neutrons. A DNA repair-deficient mutant, KS46 (uvrA-), of Escherichia coli was transformed with the plasmid DNA, and the transformants carrying mutations on the supF gene were selected as nalidixic acid-resistant colonies. The mutation frequency (2.4 x 10(-4)) of pZ189 at the D10 dose was about 70 times greater than the spontaneous rate (3.5 x 10(-6)). The plasmid mutations were analyzed using DNA sequencers; 88% of them were base substitutions. A few minus-one frameshifts (7%) and deletions (5%) were detected. Among these base substitutions, transversions of G:C to T:A (42%) and G:C to C:G (29%) predominated. Twenty-seven percent of the base substitutions were G:C to A:T transitions; no A:T to G:C transitions were detected.
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In this paper the problems associated with the "in situ" concentration techniques using MnO2 and Al2O3 as adsorbents are reviewed. Sampling equipments, radiochemical separation procedures, yield tracers, sources preparation and counting methods are described. The different behaviour of Ra, U, Th, Pu and Am is discussed and considered for future speciation studies.
Most of the results of the first systematic nationwide monitoring of public water supplies for 226Ra have been received. Approximately 50,000 public water supplies have been sampled of a total of 59,812. It is estimated that once the drinking water from all supplies has been analyzed, approx. 500 samples will exceed the Maximum Contaminant Level (MCL) of 5 pCi/l. Almost all the violations occur for ground water supplies. Monitoring in some states is incomplete but the geographical distribution of these water supplies that exceed the MCL is clear. This study is compared to other information concerning the concentration of 226Ra in drinking water supplies and the implications of this information are discussed.
There is now a significant body of data that indicate that the effects of ionising radiation may extend to more than those cells that directly suffer damage to DNA in the cell nucleus. Cells neighbouring those cells that are irradiated, or even well separated from those that are irradiated demonstrate several responses that are recorded in hit cells as a function of absorbed dose. That is, the responding non-hit cells are bystanders of hit cells. A protocol has been devised which allows for examination of one means of eliciting bystander responses, specifically, effects on non-contacting cells. Cell culture chambers are set up such that a population of cells is physically separate from the energy depositions of track segment charged particles. Absorption of energy in sub-millimetre distances in the cell culture medium ensures that one population of cells can only respond to factors generated in the irradiated medium or in another population of irradiated co-cultured cells, which may be of similar or dissimilar origin. For irradiation of medium alone, enhanced levels of micronuclei, and of delays in cell cycle progression occur in normal human fibroblasts, but not epithelial cells. This procedure allows for a defining of the factors responsible for initiating bystander effects and for determining their quantitative relevance.
A model of the DNA and electron and ion track structure computer codes are used to model damage in the DNA by direct action. This damage is converted into single-strand breaks using the method described by Charlton and Humm (1988) in which a minimum energy deposited in a critical volume of the DNA is correlated with the production of single-strand breaks. It is then assumed that if these single-strand breaks lie on opposite strands and are separated by less than a few base pairs they produce double-strand breaks. Absolute yields of both single- and double-strand breaks expressed in breaks/Gy-dalton are calculated and compared to measured yields. Good agreement is obtained for single-strand breaks while the calculated yields for double-strand breaks are greater than those measured.
The data on radiative capture through the giant resonance have led to a model in which the capture is pictured as proceeding through a single broad (and therefore short-lived) state that can be called the giant-resonance state. This state is the one formed directly upon capture of a proton, and hence most of the capture radiation is emitted quickly in the direct-interaction mode. Some of the energy that is contained in the giant-resonance state is shared with the more-complicated states of the compound nucleus (that is, with states having many excited nucleons). This sharing, in turn, gives rise to the fine structure that is observed within the giant-resonance envelope. The constant angular distributions that are observed throughout the giant-resonance region support the single-state picture of the giant resonance.
Epidemiological data from uranium miners have not been able to provide a definitive model depicting the interaction between radiation exposure and smoking in the etiology of lung cancers among miners who also smoke. Using the well-characterized C3H 10T1/2 cell system, the toxicity and oncogenic transforming incidence by either gamma-rays or He4 ions, with or without concurrent exposure to cigarette smoke condensate (CSC), were examined. He4 ions had the same energy spectrum as radon. CSC, extracted from 2R1 cigarettes, induced a dose-dependent toxicity and oncogenic transformation incidence in 10T1/2 cells. CSC, in combination with a 2 Gy dose of gamma-rays, induced a toxicity and transforming response that was largely additive in nature. Similar additive modes of interaction were also observed when CSC was combined with He4 ions at a dose that was equivalent in cell killing to that used for gamma-rays. These results provide evidence that radiation and smoking have an additive effect in oncogenic transforming potential and may provide an experimental handle towards an epidemiological uncertainty.
These studies demonstrate the feasibility of targeted therapy for the treatment of disseminated peritoneal disease using (212)Pb-labeled Herceptin as an in vivo generator of (212)Bi. In vitro studies compare the potential of the bismuth radioisotopes, (213)Bi and (212)Bi, to that of (212)Pb. Overall, (212)Pb results in a higher therapeutic index than either bismuth radioisotope, requiring lower radioactivity (microCi) for effective cytotoxic response. A pilot radioimmunotherapy (RIT) experiment treating mice bearing 5 d LS-174T intraperitoneally (i.p.) xenografts determined a maximum tolerated dose (MTD) of 20-40 microCi with i.p. administration. A specific dose response was observed and 10 microCi was selected as the effective operating dose for future experiments. Median survival of tumor-bearing mice receiving 10 microCi increased from 19 to 56 days (p = 0.008). The efficacy of (212)Pb-Herceptin was also assessed in a human pancreatic carcinoma xenograft (Shaw; i.p.) animal model previously reported as unresponsive to 213Bi-Herceptin (p = 0.002). Multiple dosing of (212)Pb-Herceptin was evaluated in both animal models. The median survival of mice bearing 3 d LS-174T i.p. xenografts increased to 110 days, with up to 3 doses of (212)Pb-Herceptin given at approximately monthly intervals; however, there was no evidence of a correlation with the second and third doses (p = 0.98). No improvement in median survival was noted with a similar regimen in the Shaw xenograft model.
The purpose of this study was to evaluate the mortality experience of persons with longstanding diabetes who had received pituitary irradiation for diabetic retinopathy compared to a matched group of persons with diabetes who had not had pituitary ablation. The irradiated cohort consisted of 167 patients treated at the Donner Pavilion (Lawrence Berkeley Laboratory, University of California, Berkeley), and the comparison cohort was the population evaluated in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Survival analyses were performed comparing the two cohorts using three different sets of matching criteria, each more restrictive than the previous analyses. The three different strategies were (1) matched only on severity of diabetic retinopathy; (2) matched on severity of retinopathy and age; and (3) matched on severity of retinopathy, age, gender, and hypertension status. Tests of comparison were the log-rank test, the Wilcoxon test, and the likelihood ratio test. For the model matching only on severity of retinopathy, mean survival was 8.3 years for the WESDR group and 9.4 years for the ablated group (p > 0.05 for all three statistical tests). For the model matched on retinopathy and age, mean survival was 8.9 years for the WESDR group and 9.2 years for the ablated group (p=0.05 log-rank test, 0.32 Wilcoxon test, and 0.06 likelihood ratio test). For the model matching on retinopathy, age, gender, and hypertension status, mean survival was 8.9 years for the WESDR group and 11.6 years for the ablated group (p=0.72 log-rank test, 0.08 Wilcoxon test, and 0.82 likelihood ratio test). These data are compatible with the notion that pituitary ablation, and therefore induced pituitary growth hormone deficiency, may not decrease survival in those with severe diabetic retinopathy.
An experimental study was conducted to characterize the full-width half-maximum values, peak shapes, and peak shifts of the energy spectra from alpha emitters in the forms of particulate matter on sampling filters and electro-deposited plated sources. Monodisperse 1.0-microns anhydrous uranium acetate aerosol particles were collected on seven types of sampling filters. Full-width half-maximum values at atmospheric pressure varied from 373 keV for a 3-microns pore size Fluoropore filter to 584 keV for a glass fiber filter. Monodisperse uranium acetate aerosols from 1.2-8.1 microns were collected on Millipore 1.2-microns pore size membrane filters to examine the self-absorption effect. Under vacuum, the corresponding full-width half-maximum values ranged from 241-1,011 keV. Successively heavier mass loadings of monodisperse 1.8-microns uranium acetate particles from 13.7-127 micrograms cm-2 caused the values to increase from 420 to 580 keV. With an electroplated 23.9-mm-diameter 239Pu source and a 25.4-mm detector, the distance between source and detector was incrementally increased from 3.2 to 6.4 mm--a range of distances that is typical of those found in alpha continuous air monitors. At atmospheric pressure, the values increased from 280 to 330 keV and the detector efficiency decreased from 30.5% to 20.9%. Tests with various sizes of sources and detectors suggest that a continuous air monitor should be designed so that the two are of approximately equal size.
In a previous paper, one of the authors suggested an analytical method for calculation of the response function of an alpha spectrometer for the case of large solid angles. This paper describes the experimental verification of the method. Spectra of a well-known natural uranium sample were measured with a 450 mm2 Si detector and compared to the theoretical predictions. The measurements were carried out with two different geometrical configurations. In both cases a good agreement was observed between experimental and theoretical results.
It has been shown that two main effects contribute to the tailing in the shapes of alpha-peaks measured with silicon detectors: the ionization loss in the source and the response of the detector. We studied the relative influence of both factors in measurements with small source-to-detector distances. The computer simulation code 'the stopping and range of ions in matter' has been used to obtain the energy spectra of a 226Ra source as a function of the source thickness. Results of the simulation are compared with experimental measurements.