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Distributions of cell populations within alpha-particle range of plutonium deposits in the rat and beagle testis.

Plutonium is not uniformly distributed in testicular tissues; thus some cell populations may receive larger or smaller radiation exposures than would be expected if the nuclide were uniformly distributed. The distributions of cell populations within alpha-particle range of Pu deposits in rat and beagle testes were determined. The data were collected from autoradiographs of testicular tissues containing 241Pu. A cell distribution factor (CDF) was determined for each cell population and is defined as the average number of each cell type within alpha-particle range of each observed Pu deposit relative to the number of each cell type that would be expected within alpha-particle range of each Pu deposit, if the deposits were distributed uniformly. In addition, the percentage of the spermatogonial stem cell population within alpha-particle range of Pu deposits was determined. In rats, the CDF for the spermatogonial stem cells is about 2.2. This value is similar to other enhancement and inhomogeneity factors reported for rodents in the literature. In beagles the CDFs to all cells in the seminiferous epithelium were less than the rats. In addition, the percentage of spermatogonial cells within alpha-particle range of Pu concentrations in the interstitial tissues was a factor of about 3 less in the dog than in the rat. The largest CDFs seen in both species were in the interstitial tissues, particularly for Leydig cells. Because the organization of testicular tissues in the beagle is quite different from rodents but more similar to human, the results from this study suggest that extrapolations from rodents to humans may tend to overestimate the potential for radiation exposure to spermatogonial stem cells as well as the fraction of the spermatogonial stem cell population at risk to exposure from internally deposited 239Pu.

Alpha Particles↗

Failure of interferon to inhibit plutonium-induced osteosarcomas in mice.

The injection of murine interferon three times weekly in dose levels of 1,250, 5,000, or 20,000 U produced no significant antitumor effect against primary 239Pu-induced osteosarcomas in C57BL/6J mice. The interferon treatment was begun 94 days after the plutonium injection, which is well before the radiographic or microscopic appearance of neoplasia, and was continued until the moribund state or death. The average radiation dose accumulated by the skeleton at the time of first treatment was approximately 300 rad. The largest dose of interferon studied, 20,000 U/injection, was approximately 3 X 10(6) U/m2 of body surface, or 10(6) U/kg body weight.

Animals↗

[Method of determining the plutonium content of wounds].

The authors proposed a method for the determination of 239Pu in wounds based on the measurement of the intensity of UL-x-ray radiation with the mean energy of 17 kev and concomitant gamma-radiation of 241Am. The correlation of the intensity of the gamma-lines of 241Am with the energies of 26.4 and 59.6 key is used for the unequivocal determination of the depth of radionuclide deposit. The isolation in the range of the gamma-line with the energy of 26.4 kev was performed using differential x-ray filters made of silver and cadmium placed in turn in front of the scintillation detector while recording radiations from a studied wound. This method ensures the required accuracy (+/- 20%) of the operative determination of plutonium in wounds employing simple and easily handled equipment.

Humans↗

[Mechanism of distribution of neptunium and plutonium in rats].

Neptunium administered intravenously together with the high molecular weight protein fraction of blood serum was almost completely accumulated by the liver after 60 min. Then neptunium left the liver and was partially deposited in the skeleton. Plutonium, being a component of a nonprotein and a low molecular weight protein fractions, was mainly found in the skeleton where it had been accumulated throughout the entire period of observation (14 days, 52-58%); as to the nonprotein fraction, the value of accumulation was somewhat higher.

Animals↗

[Change in aminotransferase and alkaline phosphatase activity in rats exposed to plutonium-239 in combination with external gamma-radiation].

Activity of alanine- and aspartate aminotransferases and alkaline phosphatase in the liver and blood serum was studied during 17 months after the administration of plutonium-239 (92.5 kBq/kg) to rats preirradiated with gamma-rays (103.2 and 51.6 mC/kg). The dynamics of changes in the activity of the enzymes under study was undulatory; the changes observed in the enzymic activity under the combined effect of the two types of radiation exhibited certain distinctions from those caused by their separate action.

Alanine Transaminase↗

Plutonium in [99mTc] Pertechnetate for clinical use: concise communication.

Pertechnetate from 31 different Tc-99m generators was analyzed to determine if alpha-emitting radionuclides were present. Significant amounts of Pu(239 + 240) were found in the pertechnetate eluted from neutron-activated molybdenum distributed by one manufacturer. The Pu(239 + 240)/Tc-99m activity ratio in the first eluate from these generators varied between 1.3 . 10(-12) and 1.4 . 10(-11). The Pu(239 + 240) contamination is believed to originate from uranium impurities in the molybdenum batch. The build-up of Am-241, the daughter decay product of Pu-241, has also been demonstrated. The estimated Pu-241/Pu(239 + 240) activity ratio at the reference time was 8:1. It is strongly recommended that upper limits for the plutonium content of eluates from nonfission-produced molybdenum should be included in the various pharmacopoeias and that restrictions be placed on the uranium content of molybdenum used for the production of Mo-99 by neutron activation.

Americium↗

Incidence of plutonium-induced bone cancer in neutered mice.

The incidence of bone cancer, after a single i.p. injection of monomeric 239Pu citrate, is significantly higher in female than in male mice. To evaluate the role of the gonads in this sex-related difference, male and female C57BL/Do (albino) mice were castrated at 40 days of age. Fifty days later, they were given injections of 239Pu. After castration, the frequency of bone sarcomas in the two sexes was approximately equal. This resulted from an increased incidence in the castrated males and a decreased incidence in the ovariectomized females as compared to the intact plutonium-treated mice.

Animals↗

Pulmonary carcinogenesis in the F344 and Wistar rat after inhalation of plutonium dioxide.

Pulmonary carcinogenesis was compared in female F344 and Wistar rats after inhalation of high-fired 239PuO2. Plutonium particle aggregation, as determined by quantitative light and scanning electron microscopic autoradiography, was greater for the F344 strain than for the Wistar strain. The median survival times were similar in control and low-dose (0.8-1.0 Gy) groups of both strains, but were significantly decreased in the high-dose (34-37 Gy) groups of both strains. Squamous metaplasia was not found in control or low-dose groups of either strain, but was found in 62-65% of high-dose groups of both strains. Adenomatous metaplasia was considerably higher in control and low-dose groups of F344 rats than in Wistar rats. A total of 87 lung tumors were found in 140 exposed F344 rats and 46 lung tumors in 176 exposed Wistar rats. The incidence of lung tumors in F344 rats was 1.7% in controls, 20% in the low-dose group and 82% in the high-dose group. The incidence of lung tumors in Wistar rats was 0.1% in controls, nil in the low-dose group and 68% in the high-dose group. About half of all lung tumors in both strains were considered to be the primary cause of death. The median survival times of rats of both strains in the high-dose groups that died with lung tumors were greater compared with rats in these groups that died without lung tumors. In contrast, these differences did not occur among rats in the low-dose groups. The absolute risk was 1900 lung tumors per 10(4) Rat-Gy for F344 rats receiving low doses and nil for Wistar rats receiving low doses, but about 210 lung tumors per 10(4) Rat-Gy for high-dose groups of both strains. The adenomatous tumor phenotype predominated in the F344 strain, while the squamous tumor phenotype predominated in the Wistar strain. Risk of squamous tumors was similar for both strains. Overall, the F344 strain appears to be more "sensitive" than the Wistar strain to formation of lung tumors at low to moderate doses from inhaled 239PuO2 due mostly to an increased incidence of adenomatous phenotype tumors.

Aerosols↗

Hepatic effects of inhaled plutonium dioxide in beagles.

The effects of inhaled 238PuO2 deposited in the liver of dogs were studied in beagles exposed to initial lung depositions ranging from 5.7 to 2979.7 Bq/g lung. Approximately 20% of the initial lung deposition was translocated to the liver by 1500 days after exposure. Life-span observations revealed that the liver contained 40% of the final body burden of plutonium, second only to the skeleton. Elevated serum liver enzyme activities were observed in dogs with final liver depositions of > or = 0.4 Bq/g, cumulative dose to the liver of > or = 0.18 Gy and annual dose rate > or = 0.02 Gy/year. Enzyme elevations were seen at one dose level lower than that in which bone or lung tumors were observed. Linear regression analysis revealed strong to moderate correlation between cumulative dose and dose rate and time to observed increases in liver enzyme activities. Liver tumors were late-occurring neoplasms observed at lower exposure levels where life span was not shortened by lung and bone tumors.

Administration, Inhalation↗

Expression of transforming growth factor alpha and epidermal growth factor receptor in rat lung neoplasms induced by plutonium-239.

Ninety-two rat lung proliferative lesions and neoplasms induced by inhaled 239PuO2 were evaluated for aberrant expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR). Expression of TGF-alpha protein, measured by immunohistochemistry, was higher in 94% of the squamous cell carcinomas and 87% of the foci of alveolar epithelial squamous metaplasia than that exhibited by the normal-appearing, adjacent lung parenchyma. In contrast, only 20% of adenocarcinomas and foci of epithelial hyperplasia expressed elevated levels of TGF-alpha. Many neoplasms expressing TGF-alpha also expressed excessive levels of EGFR mRNA. Southern and DNA slot blot analyses showed that the elevated EGFR expression was not due to amplification of the EGFR gene. These data suggest that increased amounts of TGF-alpha were early alterations in the progression of plutonium-induced squamous cell carcinoma, and these increases may occur in parallel with overexpression of the receptor for this growth factor. Together, these alterations create a potential autocrine loop for sustaining clonal expansion of cells initiated by high-LET radiation.

Animals↗

[Functional study of metal and radiation in the mechanism of toxic action of plutonium injected in its elemental form].

A ponderal variations study of rats contaminated either with the same metal mass of two isotopes 238Pu and 239Pu or with an equal activity level entitles us to conclude that plutonium toxicity for below 50 muCi/kg levels arises from particles alpha. For higher levels, about 120 muCi/kg, the quantity effect of metal has an influence on localisation and repartition of toxicity. Beneficial effect of oxygenotherapy for 120 muCi/kg appears only after a delay of several days, the time required for toxic manifestation, confirming in acute intoxication, the function of ionising radiation emitted by the metal.

Alpha Particles↗

p53, erbB-2 and K-ras gene alterations are rare in spontaneous and plutonium-239-induced canine lung neoplasia.

Inhalation of high-linear energy transfer radiation in the form of radon progeny is a suspected cause of human lung cancer. To gain insight into the types of genetic derangement(s) caused by this type of radiation, lung tumors from beagle dogs exposed to 239PuO2 and those arising in animals with no known carcinogen exposure were examined for evidence of aberrations in genes known to be altered in lung tumors. Altered expression of the p53 tumor suppressor gene and proto-oncogene erbB-2 proteins (p185erbB2) was evaluated by immunohistochemical analysis of 117 tumors representing different histological types in exposed (n = 80) and unexposed (n = 37) animals. Twenty-eight tumors were analyzed for K-ras proto-oncogene mutations by polymerase chain reaction amplification and direct sequencing. Fourteen percent (16/116) of all lung neoplasms showed elevated nuclear accumulation of p53 protein. Regardless of exposure history, adenosquamous and squamous cell cancers comprised 94% of all tumors with p53 abnormalities. Eighteen percent (21/117) of all tumors had evidence in codons 12, 13 or 61 tumors from unexposed (n = 9) or plutonium-exposed dogs (n = 19). These data indicate that p53 and K-ras gene abnormalities as a result of missense mutation are infrequent events in spontaneous and 239PuO2-induced lung neoplasia in this colony of beagle dogs. Alternative mechanisms of gene alteration may be involved in canine pulmonary carcinogenesis.

Alpha Particles↗

Lung cancer risk due to exposure to incorporated plutonium.

An epidemiological study has been carried out among 1,479 male workers who started working at the "Mayak" Production Association in 1948-1958 and were exposed to external gamma radiation and plutonium aerosols. Lung cancer mortality for the follow-up period 1948-1993 has been analyzed. No statistically significant association of lung cancer mortality and external gamma-ray dose has been revealed in the range of accumulated doses of 0.2-5.5 Gy. Association of lung cancer mortality and the dose of alpha-particle radiation to the lung is statistically significant. In the dose range below 30 Sv, this association can be described in terms of a linear nonthreshold function. Lifetime lung cancer risk in the dose range below 30 Sv is 1.21 x 10(-2)Sv(-1).

Adult↗

The inhibitor of DNA replication encoded by the Drosophila gene plutonium is a small, ankyrin repeat protein.

The plutonium (plu) gene product controls DNA replication early in Drosophila development. plu mutant females lay unfertilized eggs that have undergone extensive DNA synthesis. In fertilized embryos from plu mutant mothers, S-phase is uncoupled from mitosis. The gene is expressed only in ovaries and embryos, null alleles are strict maternal effect mutations, and the phenotype of inappropriate DNA replication is the consequence of loss-of-gene function. plu therefore negatively regulates S-phase at a time in early development when commitment to S-phase does not depend on cyclic transcription. plu encodes a protein with two ankyrin-like repeats, a domain for protein-protein interaction. plu is immediately adjacent to, but distinct from, the PCNA gene.

Amino Acid Sequence↗

The Drosophila plutonium and pan gu genes regulate entry into S phase at fertilization.

Mutations in the Drosophila maternal genes plutonium (plu) and pan gu (png) have the striking phenotype that DNA replication initiates in unfertilized eggs. Fertilized eggs from plu or png mutant mothers also have a mutant phenotype; DNA replication is uncoupled from nuclear division, resulting in giant, polyploid nuclei. Analysis of multiple alleles of these genes indicates that their wild-type function is required to maintain repression of DNA replication until fertilization. The phenotype of two png alleles suggests that this gene also may play a direct role in coupling S phase and mitosis during the early cleavage divisions. We describe genetic interactions among png, plu, and the previously identified gene gnu that demonstrate these three genes regulate the same process.

Alleles↗

Sequential isotopic determination of plutonium, thorium, americium, strontium and uranium in environmental and bioassay samples.

A procedure has been developed to provide sequential analysis of 238Pu, 230Th, 241Am, 238U, and 90Sr in environmental and bioassay samples. Tracers and/or carriers (242Pu, 243Am, 232U, and stable strontium) are added into the sample as chemical yield monitors, and then, plutonium, thorium, strontium, americium, and uranium are sequentially separated and purified by Dowex ion-exchange resin, EiChroM Sr-resin, EiChroM TRU-resin, and Chelate-100 resin, respectively. The radioactivities of 90Sr and the actinides are measured using the liquid scintillation counter and alpha-particle spectrometer, respectively. Acidified water, glass-fiber air filter, soil, synthetic urine and synthetic feces samples of US National Institute of Standard and Technology Radiochemical Intercomparison Program(NRIP) were analyzed to verify this method. All the analytical results of 238Pu, 230Th, 90Sr, 241Am and 238U meet the traceability limit per ANSI N42.22, and when appropriate, evaluation of radiobioassay measurement bias and precision per ANSI N13.30.

Chromatography, Ion Exchange↗

Plutonium oxide benchmark problems for the SOURCES code.

Neutron yields and spectra for nine plutonium oxide (PuO(2)) compositions were calculated with the SOURCES 4C computer code. In addition to five experimental measurements serving as benchmarks for the SOURCES homogenous option, neutron production information for three postulated oxide compositions is also presented. Spectral information for neutrons originating from spontaneous fission and (alpha,n) reactions with light targets is presented in tabular format for further manipulation.

Journal Article↗

Electron energy-loss spectroscopy of anomalous plutonium behavior in nuclear waste materials.

Plutonium-enriched layer has been observed in corroded spent uranium oxide fuel (CSNF). These Pu-enriched regions were examined with analytical transmission electron microscopy combined with electron energy-loss spectroscopy (EELS). The enriched region also contained U, Am, Ru, Zr, but only minor enrichment of rare earth elements. The Pu, possibly as Pu(V) according to EELS measurements, was dispersed within re-precipitated uranium oxide (identified as U3O8) nano-crystals between U(VI) secondary phases and the CSNF surface. The U, Pu, and Am enrichment was observed in the corrosion products with tests on different nuclear fuels. This may have implications for the long-term behavior of CSNF under storage in a geologic waste repository. Furthermore, there may be an increased potential for the generation of Pu-bearing colloids from this type of weathered CSNF.

Journal Article↗