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Proliferation of mouse lung epithelial cells after inhalation exposure to 239PuO2.

The aim of this study was to investigate cell proliferation in mouse lungs up to 12 weeks after exposure to 239PuO2. CBA mice were exposed (nose-only) to 239PuO2 to give an initial alveolar deposit of 500 Bq. The main morphological change observed was hypertrophy of Type II cells. The labeling index (LI) of alveolar cells, which was monitored by immunocytochemical detection of DNA-incorporated 5-bromo-2'-deoxyuridine (BrdU), increased with time after exposure and was eight times that of controls by the end of the study. The LI of the bronchiolar cells was increased markedly after exposure but declined thereafter. The cell proliferation patterns of the alveolar and bronchiolar cells (mainly Type II and Clara cells, respectively) could be related to the distribution and clearance patterns of the deposited particles of 239PuO2 and to the effects of alpha-particle radiation on these cells. This study showed that significant cellular changes, particularly cell proliferation, occurred at early times after exposure of mouse lung to 239PuO2. However, the relevance of these results to the late carcinogenic effects of 239Pu could not be assessed because of the limited duration of this study.

Administration, Inhalation↗

Experiment "Seeds" on Biokosmos 9. Dosimetric part.

The aim of the experiment "Seeds" on the Sowjetic satellite Biokosmos 9 was the observation of mutagenic effects caused at special loci of seeds of Arabidopsis thaliana and assigned to particles of the Cosmic radiation. Two types of exposure units were flown: A low-shielding unit Type I, mounted at the surface of the satellite (1.4 g/cm2 shielding) and, for comparison, an identical item inside (16 g/cm2 shielding), using nuclear emulsion as track detectors. A Type II unit, flown inside (18g/cm2 shielding) was mounted with AgCl track detectors. The layout will be briefly described. A first set of dosimetric data from the physical evaluation of the experiment will be presented. The subdivision into charge- and LET-groups shows a rather high contribution of the intermediate LET-group (350-1000 MeV/cm) due to medium heavy particles (Z = 6-10) and to enders of light (p, alpha) particles.

Arabidopsis↗

Computed LET distributions in the build-up region of tissue for 14 MeV neutrons.

Experimental radiobiological investigations of fast neutron beams involve irradiation of thin cell layers. The irradiation of cells is done either in free air or with a material such as graphite, TE plastic or bone-equivalent plastic covering the cells. This paper discusses the computed dose distributions in LET at shallow depths between 5 or 10 micrometers and the equilibrium depth, and the influence of the overlying materials on the distributions. The secondaries considered are elastic recoils of H, C, N and O, and 22 alpha particle groups and the corresponding heavy recoils arising from (n, alpha) events in C, N, O, P and Ca. Dose-average LET and curves of detailed dose distributions in LET as a function of depth in tissue are given for various overlying materials.

Energy Transfer↗

Physical and chemical mutagenesis.

Important methods to artificially induce mutations are the use of chemical and physical agents. Most chemical mutagens are alkylating agents and azides. Physical mutagens include electromagnetic radiation, such as gamma rays, X rays, and UV light, and particle radiation, such as fast and thermal neutrons, beta and alpha particles. Mutagenic treatment of seeds is the most convenient and, therefore, the standard method in seed propagated crops. Seeds can be treated in large quantities and are easily handled, stored, and shipped. It is fairly easy to repeat the conditions of mutagenic treatment, pre- and post-treatment, and hence, to obtain reproducible results within practical limits. Besides seed treatment, whole plants, cuttings, tubers, pollen, bulbs, corms, or in vitro plants or tissues can be treated. This chapter is restricted to the commonly applied techniques of mutation induction in seeds by ethyl methanesulfonate (EMS) treatment and by gamma and fast neutron irradiation.

Ethyl Methanesulfonate↗

EPR signal enhancement of alanine irradiated with thermal neutrons.

A method to enhance the electron paramagnetic resonance signal amplitude response of alanine to thermal neutrons is presented. The method is based on the production of additional free radicals caused by alpha-particle and 7Li interactions on the alanine. These particles emerge from the neutron capture 10(5)B (n, alpha) 7(3)Li reaction. For this purpose, alanine and boric acid are intimately mixed. Mixture intimacy is critical for optimum enhancement. A way to achieve good mixture intimacy is suggested. A signal enhancement up to 2200% is obtained.

Alanine↗

Glycogen in epidermal nerve terminals of Lacerta sicula (squamata: reptilia).

Proof is given that the granula occuring in the epidermal discoid nerve terminals of Lacerta sicula consist of glycogen. Staining with PA-PbCi shows 300 A sized alpha-particles and 70 A sized beta-particles. The electron-dense boundary appearing after digestion with alpha-amylase consists of limit-dextrins.

Animals↗

Rapid identification and analysis of airborne plutonium using a combination of alpha spectroscopy and inductively coupled plasma mass spectrometry.

Recent wildland fires near two U.S. nuclear facilities point to a need to rapidly identify the presence of airborne plutonium during incidents involving the potential release of radioactive materials. Laboratory turn-around times also need to be shortened for critical samples collected in the earliest stages of radiological emergencies. This note discusses preliminary investigations designed to address both these problems. The methods under review are same day high-resolution alpha spectroscopy to screen air filter samples for the presence of plutonium and inductively coupled plasma mass spectrometry to perform sensitive plutonium analyses. Thus far, using modified alpha spectroscopy techniques, it has been possible to reliably identify the approximately 5.2 MeV emission of 239Pu on surrogate samples (air filters artificially spiked with plutonium after collection) even though the primary alpha-particle emissions of plutonium are, as expected, superimposed against a natural alpha radiation background dominated by short-lived radon and thoron progeny (approximately 6-9 MeV). Several processing methods were tested to prepare samples for analysis and shorten laboratory turn-around time. The most promising technique was acid-leaching of air filter samples using a commercial open-vessel microwave digestion system. Samples prepared in this way were analyzed by both alpha spectroscopy (as a thin-layer iron hydroxide co-precipitate) and inductively coupled plasma mass spectrometry. The detection levels achieved for 239Pu--approximately 1 mBq m(-3) for alpha spectroscopy screening, and, < 0.1 mBq m(-3) for inductively coupled plasma mass spectrometry analysis--are consistent with derived emergency response levels based on EPA's Protective Action Guides, and samples can be evaluated in 36 to 72 h. Further, if samples can be returned to a fixed-laboratory and processed immediately, results from mass spectrometry could be available in as little as 24 h. When fully implemented, these techniques have the potential to provide useful information and improved operational flexibility to emergency planners and first-responders during radiological emergencies.

Air Pollution, Radioactive↗

1987 Douglas Lea memorial lecture. Particle dosimetry in bone and the toxicity of bone-seeking radionuclides.

Consideration is given to the tissues at risk in bone and a Monte Carlo method is described which determines the absorbed dose to endosteal tissues and marrow in trabecular bone. The method synthesizes random tracks through the trabecular structures that deposit energy along a path through any given trabecular cavity. The path lengths through the trabeculae and marrow cavities are measured with a bone-scanning microscope and other bone data, such as trabecular surface areas, can also be derived. Results are given for human bones and for bones of the beagle, miniature pig and rhesus monkey. They show that, for the same radionuclide concentration, the doses to endosteal tissues and bone marrow are several times greater in animal than in human bone, and that higher doses in human bone from the Ca and Sr radionuclides are obtained if the initial deposition on bone surfaces is allowed for. Other studies show that the occurrence of osteosarcoma in the human long bones correlates well with trabecular surface area and also that, unlike the case of beta-particles from 90Sr+90Y, leukaemia is not a significant consequence of the alpha-particle doses from 226Ra in human bone or from 226Ra, 239Pu and other alpha emitters in beagle bone.

Bone Neoplasms↗

A CAM (continuous air monitor) sampler for collecting and assessing alpha-emitting aerosol particles.

A new continuous air monitor (CAM) sampler for assessing alpha-emitting transuranic aerosol particles has been developed. The system has been designed to permit collection of particles that can potentially penetrate into the thoracic region of the human respiratory system. Wind tunnel testing of the sampler has been used to characterize the penetration of aerosol to the collection filter. Results show that greater than or equal to 50% of 10-micrograms aerodynamic equivalent diameter (AED) particles are collected by the filter at wind speeds of 0.3 to 2 m s-1 and at sampling flow rates of 28 to 113 L min-1 (1 to 4 cfm). The deposition of 10-microns AED particles takes place primarily in the center of the filter, where the counting efficiency of the detector is highest.

Aerosols↗

Genetic, cytogenetic, and carcinogenic effects of radon: a review.

Radon exposure has been linked to lung carcinogenesis in both human and animal studies. Studies of smoking and nonsmoking uranium miners indicate that radon alone is a risk factor for lung cancer at the levels encountered by these miners, although the possibility exists that other substances in the mine environment affect the radon-induced response. The relevance of data from mines to the lower-exposure home environment is often questioned; still, a recent study of miners exposed to relatively low radon concentrations demonstrated a statistically significant increase for lung and laryngeal cancer deaths. In two major series of experiments with rats, the primary carcinogenic effect found was respiratory tract tumors, and evidence for an inverse exposure-rate effect was also noted. Although this inverse dose-rate effect also has been described in underground miner studies, it may not similarly apply to radon in the home environment. This observation is due to the fact that, below a certain exposure, cells are hit once or not at all, and one would not expect any dose-rate effect, either normal or inverse. Because some chromosome aberrations persist in cycling cells as stable events, cytogenetic studies with radon are being performed to help complete the understanding of the events leading to radon-induced neoplasia. Radon has been found to induce 13 times as much cytogenetic damage (as measured by the occurrence of micronuclei) than a similar dose of 60Co. A wide variety of mutation systems have demonstrated alpha-particle mutagenesis; recent investigations have focused on the molecular basis of alpha-induced mutagenesis. Gene mutations are induced by radon in a linear and dose-dependent fashion, and with a high biological effect relative to low-LET irradiation. Studies of the hprt locus show that approximately half of the alpha-induced mutations arise by complete deletion of the gene; the remaining mutations are split between partial deletions, rearrangements, and events not detectable by Southern blot or PCR exon analysis. Although other mutation systems do not show the same spectra as observed in the hprt gene (suggesting that the gene environment affects response), DNA deletions or multilocus lesions of various size appear to be predominant after radon exposure. As data emerge regarding radon-induced changes at the chromosomal and molecular level, the mechanisms involved in radon carcinogenesis are being clarified. This information should increase the understanding of risk at the low exposure levels typically found in the home.

Animals↗

Simulation of special bubble detectors for PICASSO.

The PICASSO project is a cold dark matter (CDM) search experiment relying on the superheated droplet technique. The detectors use superheated freon liquid droplets (active material) dispersed and trapped in a polymerised gel. This detection technique is based on the phase transition of superheated droplets at about room temperature and ambient pressure. The phase transition is induced by nuclear recoils when an atomic nucleus in the droplets interacts with incoming subatomic particles. This includes CDM particles candidate as the neutralino (a yet-to-discover particle predicted in extensions of the standard model of particle physics). Simulations performed to understand the detector response to neutrons and alpha particles are presented along with corresponding data obtained at the Montreal Laboratory.

Computer Simulation↗

Growth factor biomarkers associated with estrogen- and radiation-induced breast cancer progression.

Breast cancer is the most common cancer in women worldwide. Transformation of a normal cell to a malignant one results from mutations in genes that encode key regulatory proteins. Growth factors are proteins secreted by a variety of transformed cells and tumors and function as autocrine regulators of growth. Biomarkers associated with cancer were examined in human breast epithelial cells transformed by high-LET radiation in the presence of 17beta-estradiol. An established cancer model was used in these studies. The MCF-10F cells that were irradiated with double doses of alpha-particles in the presence of estrogen (60 cGy + E/60 cGy + E, named Alpha 5) showed gradual phenotypic changes relative to control, including tumorigenicity in heterologous animals. Protein expression was determined by quantification of immunofluorescence staining coupled with confocal microscopy. The transforming growth factor alpha, epidermal growth factor, ERK1 and fibroblast growth factor-1 (Int2) protein expression was analyzed. Increased protein expression was observed in non-tumorigenic and tumorigenic alpha-irradiated and estrogen-treated cells. However, Stat-1alpha and pS2 protein expression was only increased in the tumorigenic Alpha 5 and Tumor 2 cell lines. It can be concluded that high-LET radiation in the presence of estrogen-induced changes in the proteins associated with growth factors and their overexpression may be a critical step in the cascade of events that characterize progression in breast cancer.

Biomarkers↗

Lack of ability of trypsin-treated mitochondrial F1-ATPase to bind the oligomycin-sensitivity conferring protein (OSCP).

Soluble beef-heart mitochondrial F1-ATPase modified in its alpha-subunit by mild trypsin treatment (alpha'-F1) can no longer bind oligomycin-sensitivity conferring protein (OSCP) but is still capable of binding to F1-depleted submitochondrial particles, giving rise to a maximally oligomycin-sensitive ATPase, provided the particles contain their native complement of OSCP. When OSCP is removed from the particles, alpha'-F1 can still bind to the particles, but added OSCP induces only a low degree of oligomycin sensitivity. The possible role of OSCP in the functional coupling of the catalytic (F1) and H+-translocating (Fo) moieties of mitochondrial ATPase is discussed. The results suggest a functional similarity between the OSCP component of mitochondrial ATPase and the delta-subunit of E. coli ATPase, which is in accordance with the structural homology recently found to exist between the two polypeptides.

Adenosine Triphosphatases↗

Glycogen of high molecular weight from mammalian muscle.

Glycogen of high molecular weight has been isolated from mammalian muscle, in contrast to the material of low molecular weight commonly described. The large polysaccharide is similar to liver glycogen in the structure of its individual beta-particles and also, partially, in the mode of assembly into the gross alpha-particles. The large particles may be disrupted by 2-mercaptoethanol, but not to the same extent as their liver counterparts.

Animals↗

Nuclear interactions in proton therapy: dose and relative biological effect distributions originating from primary and secondary particles.

The dose distribution delivered in charged particle therapy is due to both primary and secondary particles. The secondaries, originating from non-elastic nuclear interactions, are of interest for three reasons. First, if fast Monte Carlo treatment planning is envisaged, the question arises whether all nuclear interaction products deliver a significant contribution to the total dose and, hence, need to be tracked. Second, there could be an enhanced relative biological effectiveness (RBE) due to low energy and/or heavy secondaries. Third, neutrons originating from nuclear interactions may deliver dose outside the target volume. The particle yield from different nuclear interaction channels as a function of proton penetration depth was studied theoretically for different proton beam energies. Three-dimensional dose distributions from primary and secondary particles were simulated for an unmodulated 160 MeV proton beam with and without including a slice of bone material and for a spread-out Bragg peak (SOBP) of 3 x 3 x 3 cm3 in water. Secondary protons deliver up to 10% of the total dose proximal to the Bragg peak of an unmodulated proton beam and they affect the flatness of the SOBP. Furthermore, they cause a dose build-up due to forward emission of secondary particles from nuclear interactions. The dose deposited by d, t, 3He and alpha-particles was found to contribute less than 0.1% of the total dose. The dose distal to the target volume caused by liberated neutrons was studied for four proton beam energies in the range of 160-250 MeV and found to be below 0.05% (2 cm distal to SOBP) of the prescribed target dose for a 3 x 3 x 3 cm3 target. RBE values relative to 60Co were calculated proximal to and within the SOBP. The RBE proximal to the Bragg peak (100% dose) is influenced by secondary particles (mainly protons and a-particles) with a strong dose dependency resulting in RBE values up to 1.2 (2 Gy; inactivation of V79). Depending on the endpoint considered, secondary particles cause a shift in RBE by up to 8% at 2 Gy. In contrast, the RBE in the Bragg peak is almost entirely determined by primary protons due to a decreasing secondary particle fluence with depth. RBE values up to 1.3 (2 Gy; inactivation of V79) at 1 cm distal to the Bragg peak maximum were found. The inactivations of human skin fibroblasts and mouse lymphoma cells were also analysed and reveal a substantial tissue dependency of the total RBE. The outcome of this study shows that elevated RBE values occur not only at the distal edge of the SOBP. Although the variations are modest, and in most cases might have no observable clinical effect, they might have to be considered in certain treatment situations. The biological effect downstream of the target caused by neutrons was analysed using a radiation quality factor of 10. The biological dose was found to be below 0.5% of the prescribed target dose (for a 3 x 3 x 3 cm3 SOBP) but depends on the size of the SOBP. This dose should not be significant with respect to late effects, e.g. cancer induction.

Animals↗

Glycogen changes in the liver cells of young rats following isoprenaline treatment. (Histochemical and ultrastructural investigations).

Glycogen changes were investigated by light and electron microscopy in the liver cells of newborn rats following isoprenaline (IPR) treatment either for 1 day (2 intraperitoneal injections at 12 h interval), or for 8 days (2 intraperitoneal injections daily). On the day following the interruption of both treatments glycogen depletion was observed as compared to control rats, as evaluated by PAS reaction and confirmed by higher total phosphorylase activity. During this stage electron microscopy revealed mainly alpha-particles of glycogen associated to highly dilated smooth endoplasmic reticulum (SER) after 1-day-treatment, and to mostly increased SER after prolonged treatment. In the animals submitted to prolonged IPR administration and sacrificed at later times, glycogen masses intensely PAS-positive were strongly increased, while the activity of total phosphorylase proved accordingly lower than in the rats sacrificed at earlier times. Electron microscopy examination confirmed an increased amount of glycogen (alpha- and beta-particles) differently distributed: beta-particles were more numerous in the liver of the rats sacrificed on the last day of the experiment. At this time SER didn't appear modified as compared to control rats.

Animals↗

Theory of passive measurement of radon daughters and working levels by the nuclear track technique.

A theoretical basis is described for long-term measurement of the activities of the alpha emitters in air by the track-etching technique. Inference of the other activities allows working levels to be derived. A set of absorber foils allows the differing response to alpha particles of different energies to be used to identify the relative abundance of the alpha emitters and the importance of diffusion to surfaces. The method is appropriate to measuring long-term exposures to radon atmospheres in homes or mines.

Air Pollutants↗

[Radon and domestic exposure].

Radon is a noble gas derived from the decay of radium, which itself is a decay product of uranium. The decay products of radon can collect electrostatically on dust particles in the air and, if these particles are inhaled and attach to bronchial epithelium, produce a high local radiation dose. Alpha particles can induce DNA double-strand breaks and the development of cancer. A causal relation between lung cancer and radon exposure and its progeny has been demonstrated in epidemiological studies of miners. Radon exposure became a public health issue almost 15 years ago. Most radon exposure occurs indoors, predominantly in the home. There is however, a wide range of radon concentration values in different countries. The highest level occurs in areas with granite and permeable soils. The risk for smoking, the leading cause of lung cancer, is far greater than for radon, the second leading cause. The estimates obtained from case-control studies of indoor radon are very contradictory. Scientific knowledge of effects of low levels of exposure to radon and the role of cigarette smoking, as a combined factor, must be studied. Smoking and radon probably interact in a multiplicative fashion.

Air Movements↗