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PubMed1987

Distribution of 239Pu in the skeleton of the tree shrew (Tupaia belangeri) between 15 and 50 months after injection.

The macroscopic and microscopic distribution of intramuscularly injected, essentially monomeric, 239Pu was studied in the skeleton of the adult tree shrew (Tupaia belangeri). Data for the period between 15 and 50 months after injection are presented and compared with the data from earlier time points. Between 83 and 500 days after injection the nuclide content and the wet weight of the skeleton decreased to a constant level at about 55 per cent of the maximum values. The microscopic distribution has been analysed in distal femora, proximal humerus, proximal tibia and lumbar vertebra over the whole observation time; additionally at some selected time points proximal femur, femur shaft, distal humerus and distal tibia were analysed. The initial endosteal surface activity ranged from 3.8 to 5.3 Bq/cm2 and decreased to a minimum at about 1000 days after injection and increased thereafter. A similar behaviour was found for the dose rate near bone surfaces which was initially about 0.075 Gy/day on endosteal surfaces. In the deep bone and the deep marrow the dose rate was negligible, about 0.008 Gy/day and 0.001 Gy/day, respectively. The average cumulative dose 1500 days after injection was about 67 Gy on the endosteum, six times greater than the cumulative dose calculated from the mean concentration of plutonium in the whole skeleton. All values are normalized to an injected activity of 37 kBq/kg body weight. The tupaia data are discussed in relation to the available data from monkeys, dogs and rats.

Animals↗
PubMed1989

Efficacy and toxicity of N,N',N",N"'-tetra(2,3,4-trihydroxybenzoyl)-spermine for decorporation of 239Pu from mice.

Male SAS/4 mice were injected i.v. with 6.6 kBq 239Pu-citrate. After 1 or 24 h a single i.p. injection of 15 or 30 mumol kg-1 or repeated (three or four) daily injections of 30 mumol kg-1 of tetra-THB-spermine were given, and at 4 or 7 days Pu retention was measured in liver, kidneys and femur. Besides tetra-THB-spermine, equimolar doses of tetra-DHB-spermine were injected for comparison, or equimolar doses of diethylene triamine-pentaacetic acid (DTPA) as a reference compound. Histological changes in kidneys and liver were examined after i.p. injections of 30 mumol kg-1 or at 2-13 times higher doses of tetra-THB-spermine. The results show that: (1) Introduction of an additional hydroxy group into the aromatic moieties of tetra-DHB-spermine results in increased hydrophilicity, lower toxicity and a lower renal retention of Pu. (2) Tetra-THB-spermine and tetra-DHB-spermine are similarly effective in removing plutonium from liver and bone. Their efficacies in removing Pu from bone are approximately similar to those of DTPA but for whole-body removal they are generally inferior. (3) Multiple (30 mumol kg-1) of tetra-THB-spermine were no more effective than a single injection at mobilizing Pu from the liver. (4) Four injections of tetra-THB-spermine induced cloudy swelling and fatty degeneration in epithelial cells of the proximal convoluted tubules. At levels of 400 mumol kg-1 tetra-THB-spermine produced severe degenerative glomerular lesions, foci of liver necrosis and thromboses of the portal vein branch.

Animals↗
PubMed1992

Alpha-irradiation of haemopoietic tissue in pre- and postnatal mice: 2. Effects of mid-term contamination with 239Pu in utero.

The distribution of 239Pu in various tissues of foetal and postnatal offspring of pregnant mice, injected i.v. at 13 days gestation with 30 kBq 239Pu/kg (in some cases with 10 or 100 kBq/kg), together with the numbers of haemopoietic progenitors in the bone marrow, spleen and liver, were measured through to 1 year post-partum. The quality of the haemopoietic microenvironment in these mice was also measured using the renal-capsule implant method. The largest radiation dose received by any haemopoietic organ was that in the liver, amounting to 10-14 mGy, as reported previously. In spite of normal numbers of haemopoietic spleen colony-forming cells (CFC-S) in the liver and seeding, at birth, into the bone marrow where the level of plutonium was minimal, a long-term deficit in their number rapidly developed. The development of the stromal microenvironment, however, was also deficient, suggesting that the dose of alpha-irradiation to the foetal liver was sufficient to cause sublethal damage in those cells destined to become the precursors of the supportive haemopoietic microenvironment in bone marrow and spleen. The results of this study suggest that although the placenta affords significant shielding to the tissues of the developing foetus from maternal contamination, the long-term effects on haemopoiesis are comparable to those in mice contaminated as adults. This further implies that the developing haemopoietic tissues are exquisitely sensitive to 239Pu contamination.

Alpha Particles↗
PubMed1993

Early chelation therapy for injected Pu-238 and Am-241 in the rat: comparison of 3,4,3-LIHOPO, DFO-HOPO, DTPA-DX, DTPA and DFOA.

Chelating agents were tested for removal of simultaneously injected Pu-238 and Am-241 from the rat. The effectiveness of early single chelate injections of Pu-238 retention in tissues decreased in the order 3,4,3-LIHOPO > DFO-HOPO > DTPA > DTPA-DX, and for Am-241 in the order 3,4,3-LIHOPO > DTPA-DX > DTPA >> DFO-HOPO. DTPA-DX showed a special ability to remove Am-241 from the liver. Injected 3,4,3-LIHOPO decreased the contents of Pu-238 in bone and liver to 9 and 3%, respectively, of those in untreated controls. Corresponding values for Am-241 in bone and liver were 30 and 6%, respectively, which indicates that 3,4,3-LIHOPO (unlike DFO-HOPO) is not a plutonium-specific chelator. The effectiveness of prompt single oral treatment with 3,4,3-LIHOPO and DFO-HOPO in reducing retention of actinides was comparable with that of those chelators injected with 1 h delay and at one-third of the oral dose. When 3,4,3-LIHOPO was administered by continuous infusion, a superior effect was achieved with total chelate amounts only slightly exceeding that given as single injection. The retention of PU-238 and Am-241 in bones was reduced to < 5 and 10% of controls, respectively; the contents in the liver were < 2% of controls.

Administration, Oral↗
PubMed1998

FISH-based analysis of stable translocations in a Techa River population.

PURPOSE: Measurements of symmetrical translocations by fluorescence in situ hybridization (FISH) were performed for retrospective biodosimetry in a Techa River population exposed to external (gamma-rays) and internal (90Sr, 137Cs) irradiation. MATERIALS AND METHODS: Chromosome analyses were carried out on peripheral lymphocytes from 73 radiation-exposed residents from settlements along the Techa River (Southern Urals, Russia) located 7-148 km downstream from the site of release of liquid radioactive waste from the plutonium production facility Mayak. Thirty-nine unexposed persons from non-contaminated areas were used as controls. Whole-chromosome painting probes for chromosomes 1, 4 and 12 were used simultaneously with a pancentromeric probe. RESULTS: A significantly elevated mean translocation frequency compared with controls was found for the total study group and for either of two subgroups of inhabitants residing in villages of the upper regions of the Techa River (7-60 km) during 1950 to 1951, or in villages of the lower regions (78-148 km) until the time of blood sampling. Within the first subgroup, subjects born between 1937 and 1949 showed higher translocation frequencies than those born between 1914 and 1936. Collective biodosimetry estimates for the various groups were between 0.24 and 0.54 Gy. Individual dose estimates for seven subjects with at least five translocations ranged between 0.77 and 1.80 Gy and compared well with doses reconstructed on the basis of 90Sr whole-body counts (WBC) and electronic paramagnetic resonance (EPR) measurements. Individual translocation frequencies from 40 subjects with existing WBC data and calculated cumulative red bone marrow doses below 0.6 Gy fall within the 95% prediction limits of the calibration curve. CONCLUSIONS: FISH-based translocation measurements can provide useful information for a retrospective biodosimetric interpretation. However, with the analysed number of cells, individual estimates required for a reliable evaluation of this highly variable exposure situation can be obtained only for a minority of subjects. In addition, influence of a temporal decline on the yield of stable translocations cannot be fully excluded.

Body Burden↗
PubMed1999

Chromosomal instability in haemopoietic cells of the foetus, mother and offspring after in utero irradiation of the CBA/Ca mouse.

PURPOSE: The present study was conducted to test the susceptibility of the mouse foetus to transmit chromosomal instability to the haemopoietic stem cells of offspring after in utero X-or plutonium-239-irradiation. MATERIALS AND METHODS: Pregnant CBA/Ca-mice were injected with 80 kBq/kg 239Pu or X-irradiated with 1 Gy X-rays on days 13 or 14 of gestation. CFU-A cultures were grown from haemopoietic stem cells sampled from foetal liver and the bone marrow from the offspring and from the mother. Non-clonal, unstable chromosomal aberrations were scored in metaphases from individual stem cell colonies. RESULTS: The relative excess (RE) of unstable chromosomal aberrations in foetal liver cells irradiated with 1 Gy X-rays increased from 1.6 at day 2 up to 2.7 at day 4 after irradiation. In the bone marrow cells from the mother, this value was 1.8 (average from cells sampled at days 3 and 14 after irradiation). After injection of the pregnant mice with 235Pu, the yield of unstable chromosomal aberrations per cell was 0.14+/-0.03 (RE approximately 10) in descendants of bone marrow cells from the mother, 0.11+/-0.02 (RE = 10) in descendants of foetal liver cells and 0.16+/-0.05 (RE = 10) in descendants of bone marrow cells from the offspring. CONCLUSIONS: From the numerical analysis of non-clonal, unstable aberrations in haemopoietic cells from the foetus, the mother and the offspring after in utero irradiation, it was concluded that in utero irradiation of the CBA/Ca mouse was not more efficient in inducing chromosomal instability in the offspring than in the foetus or the mother. All three cell populations exhibited a similar degree of unstable aberrations, both in terms of the absolute numbers of non-clonal aberrations and in terms of relative excess compared with unexposed controls.

Animals↗
PubMed1994

Interleukin 7-dependent B lymphocyte precursor cells are ultrasensitive to apoptosis.

We have compared the sensitivity of clonogenic interleukin 7 (IL-7)-dependent murine B cell precursors with that of clonogenic mature B cells and myeloid precursors to alpha-particles from plutonium-238 and X radiation. All three populations are relatively sensitive, but B cell precursors are ultrasensitive. This differential sensitivity is also observed with corticosteroid, etoposide, and cisplatin, all apoptosis-inducing drugs used in the treatment of leukemia and other cancers. Further, we show that x-rays and drugs induce the bulk of the B cell precursor population to undergo rapid apoptosis, despite the continued presence of IL-7. B cell precursors were found to express very low levels of BCL-2 protein compared with mature splenic B cells and their resistance to x-rays and corticosteroid could be enhanced by expression of a BCL-2 transgene. These data have important implications for normal lymphopoiesis and for the behavior of leukemic lymphoid precursor cells.

Alpha Particles↗
PubMed2003

An analysis of a puncture wound case with medical intervention.

A worker noted a small wound to his thumb when leaving a work site that was undergoing decontamination because of past operations with plutonium (Pu) and americium (Am). Direct surveys of the wound site confirmed the presence of contamination. The chelating agent Ca-DTPA was administered via a nebuliser within an hour after discovery of the wound. External measurements were made of the wound site and wound dressings; 24-h urinary excretion data were collected periodically and the Pu and Am urine content was determined. Zn-DTPA was administered on three occasions. The ICRP Pu systemic model was modified to consider the enhanced urinary excretion following administration of the chelating agents. The analysis indicated that the wound resulted in an initial deposition of 400 Bq 238Pu, 2240 Bq (239/240)Pu and 1060 Bq 241Am. About 70% of the initial wound activity was removed by surgical procedures and less than 1% of the wound activity was removed by chelation therapy. This paper compares the observed urinary excretion data with that indicated by a simulation of the kinetics of the transfer from the wound site and the kinetics of the chelating agent and Pu.

Administration, Inhalation↗
PubMed2003

Efficacy of 3,4,3-LI(1,2-HOPO) for decorporation of Pu, Am and U from rats injected intramuscularly with high-fired particles of MOX.

This study aimed to assess the efficacy of 3,4,3-LI(1,2-HOPO) for reducing uranium, plutonium and americium in rats after intramuscular injection of (U-Pu)O2 particles (MOX). Sixteen rats were contaminated by intramuscular injection of a 1 mg MOX suspension and then treated daily for 7 d with LIHOPO (30 or 200 micromol kg(-1)) or DTPA (30 micromol kg(-1)). LIHOPO was inefficient for removing Pu, Am and U from the wound site. However, it reduced Pu retention in carcass and liver by factors of 2 and 6 respectively, and Am retention in carcass and liver by factors of 10 and 30. In contrast, the effect of LIHOPO on U was to decrease the retention in kidneys by a factor of 75. These results confirm that LIHOPO is a good candidate for use after contamination with MOX, in combination with localised wound lavage or surgical treatment aimed at removing most of the contaminant at the wound site.

Americium↗
PubMed2001

Distribution of natural thorium in the tissues of a whole body.

The distribution of thorium in the tissues of a whole body donor to the United States Transuranium and Uranium Registries is described. This case, identified by the USTUR as Case 0212, had two documented intakes of plutonium and americium from occupational accidents while employed at Hanford but no known occupational exposure to thorium. Concentrations of 239+240Pu, 241Am, and 232Th in the tissues are compared and the distribution of these isotopes in this case is evaluated. The distribution data for 232Th are compared to those from previous studies of thorium in human tissues resulting from environmental exposure and to an individual exposed to Thorotrast (colloidal ThO2) in a medical diagnostic procedure. The 232Th distribution data from this work are also compared against ICRP 30 and ICRP 69 models for the behaviour of thorium in the human body.

Americium↗
PubMed1998

Retrospective dosimetry related to chronic environmental exposure.

Radioactive contamination of the environment occurred in the early fifties as a result of the releases from the Mayak plutonium production complex (Southern Urals, Russia). The releases of liquid wastes into the Techa river resulted in chronic exposure of 30,000 residents of the riverside communities. Since 1951 90Sr body burdens have been measured for over half of this cohort. This paper presents the analysis of data on 90Sr in humans and describes the reconstruction of internal doses for these people.

Autopsy↗
PubMed2004

Chromosomal aberrations in lymphocytes of peripheral blood among Mayak facility workers who inhaled insoluble forms of 239PU.

A cytogenetic study was performed on 79 plutonium (Pu) workers chronically exposed to alpha radiation from inhaled, low-transportable (insoluble) compounds of airborne 239Pu and to external gamma rays. Body burden estimates for 239Pu ranged from 0 to 15.5 kBq. Chromosomal aberrations (CAs) (stable and unstable) among peripheral blood lymphocytes and cumulative alpha radiation doses were evaluated approximately 25 y after first contact with 239Pu. For the cytogenetic analyses, a standard two-day peripheral blood lymphocyte culture technique was applied. While alpha radiation doses continually increase up to the time of cytogenetic measurements, significant gamma ray exposures essentially ceased long before the time of measurement, so that alpha and gamma doses were not correlated. For the exposed workers, the mean 239Pu body burden (estimate), evaluated at the time of the cytogenetic measurement, was 1.23 +/- 0.26 kBq and the corresponding mean absorbed external gamma ray dose (estimate) to the total body was 0.076 +/- 0.009 Gy. Single and multivariate regression analyses were performed on the CA data. Stable, unstable and total aberrations increased as the 239Pu body burden increased over the range 0-4.5 kBq. However, above this range little additional increase was observed. CAs were weakly correlated with time since the first intake of 239Pu. No relationship between chromatid aberrations and 239Pu incorporation was found. Unstable (but not stable) aberrations were correlated with gamma radiation dose. No significant relationship of CA and smoking was found.

Adult↗
PubMed1983

The relative importance of uptake and surface adherence in determining the radionuclide contents of subterranean crops.

The adherence of Pu-bearing particles to external surfaces of carrots, turnips, red potatoes, and sweet potatoes accounted for greater than or equal to 93% of their total Pu content. Uptake, which was measured as Pu content in peeled crops, accounted for less than or equal to 7%. Plutonium concentrations in most peeled crops were below background, and consequently, uptake could not be conclusively demonstrated. However, uptake accounted for most of the 137Cs, 40K, and 226Ra contents of subterranean crops. Concentration ratios for total radionuclide contents (i.e. surface adherence plus uptake) ranged from 3.9 X 10(1) for 40K, to 1.1 X 10(-2) for 239, 240Pu. Approximately 1.5 X 10(-3) pCi 239, 240Pu adhered per cm2 of subterranean crop surface per 1 pCi Pu/g of soil.

Cesium Radioisotopes↗
PubMed1983

Fragmentation of inhaled 238PuO2 particles in lung.

Beagle dogs were exposed by inhalation to monodisperse aerosols of 238PuO2. Autoradiographs of lung sections were studied for nine dogs sacrificed from 4 to 730 days after exposure. Fragmentation of particles in lung was observed autoradiographically. A simple mathematical model fitted to the fragmentation and lung retention data for dogs suggests that lung clearance from intact particles (65%) and particle fragments (32%) were important to the removal of 238PuO2 deposited in the lung by inhalation. The increased surface area resulting from fragmentation should increase dissolution and risk to other organs from irradiation by translocated plutonium.

Aerosols↗
PubMed1983

Measurement techniques for radium and the actinides in man at the Center for Human Radiobiology.

Various techniques are employed to determine the amounts, retention, and distribution of radioactivity in human subjects in vivo. The principal method is gamma-ray spectrometry with large NaI(Tl) scintillation crystals ("whole-body counting"). The geometries used include an arc of 1.5-m radius in which all parts of the body are roughly equidistant from the detector, a reclining chair and a flat bed with detectors placed above and below the subject. When a sufficient amount of radioactivity is present in a subject, scanning techniques assist in determining its distribution in the body. Specialized instruments such as a xenon-filled proportional counter and a dual-crystal (phoswich) detector are used to measure low-energy photon emitters, primarily plutonium and americium. americium. There are three primary methods of calibrating the detectors. The first is analytical, in which a rigorous mathematical treatment is employed; the second involves the administration of tracer amounts of radioactivity to human volunteers; the third consists of determining detector response to known amounts of radioactivity in a phantom. All three methods can be intercompared, and further evaluated by comparing the results of measurements in vivo with those of postmortem analyses. For both radium and thorium cases measured in vivo, the interpretation of the results is complicated by the fact that neither radium nor thorium emit gamma rays of any consequence. Instead, the observed gamma rays result from the decay of 214Bi (RaC) and 208Tl (ThC"), respectively. Since each of these nuclides is preceded in the decay chain by an isotope of the noble gas radon, some of which is exhaled, its activity is not equal to that of the parent radium or thorium. Therefore, breath samples are collected to determine the exhalation rate of the precursor isotope, 222Rn (radon) or 220Rn (thoron). The total body content is then the sum of the gamma activity and the exhaled radioactivity, referred to as the retained and emanating fractions, respectively.

Actinoid Series Elements↗
PubMed1983

A melanoma case-control study at the Los Alamos National Laboratory.

We conducted a melanoma case-control study at the Los Alamos National Laboratory to investigate whether related occupational exposures or personal characteristics of employees could be identified. This study was prompted by a recent report from the Lawrence Livermore National Laboratory that melanoma was much more frequent than expected among employees and that persons suffering from melanoma more often worked as chemists. Our investigation did not uncover an association with plutonium body burden, cumulative external radiation exposure, or employment as a chemist or a physicist. The major finding was that cases were more educated than controls. Melanoma risk was 2.11 among college-educated employees and increased to 3.17 among those with graduate degrees (Mantel-extension linear trend probability = 0.038). This finding is consistent with the often reported increased melanoma incidence among persons of higher social class. It points to personal characteristics, particular to persons of higher educational attainment, as risk factors for melanoma at the Los Alamos National Laboratory.

Adult↗
PubMed1984

Systemic burden and body burden of Pu in man: comparison of results from bioassay and autopsy.

A case of plutonium deposition in man within the range of 190 Bq by inhalation from about 12 yr ago is reported. An estimate of systemic burden was made based on analyses of urine and faeces and the models of Langham, Beach/Dolphin, and Durbin while the individual was alive. This estimate was compared with autopsy findings (spleen, thyroid, blood, lung, pulmonary and tracheobronchial lymph nodes, liver, skeleton). According to autopsy findings, the systemic burden (mainly liver and skeleton) had been overestimated by a factor of 11-16, the body burden (whole body) by a factor of 6-9.

Body Burden↗
PubMed1986

Determination of 241Pu in low-level radioactive wastes from reactors.

Plutonium-241 is unique in low-level radioactive wastes (LLW) from nuclear power plants because it is the only significant beta-emitting transuranic nuclide in LLW, has a relatively short half-life of 14.4 y, and has a fairly high allowable concentration for shallow land burial. Radiochemical separation of Pu followed by liquid scintillation analysis was used to quantitate 241Pu in a wide range of solid, semi-solid, and liquid LLW samples from two nuclear plants in Michigan. The 241Pu concentrations varied considerably by sample type and reactor operational period as did their correlation with 137Cs, 144Ce, 239Pu and 240Pu concentrations in the same sample. These patterns were also found in reported data for 241Pu in LLW from other reactors, raising the difficulty of accurately determining the inventory (or source term) in a LLW shallow land burial site and its implications for predicting and controlling the future environmental and public health impacts of such disposal.

Cerium Radioisotopes↗