Disorders of hematopoiesis induced by plutonium-239 dioxide

A large-dispersed plutonium 239 dioxide intravenously administered to rats in doses of 92.5, 46.3, 23.2 kBq/kg of body mass was shown to impair haemopoiesis which was manifested by a more profound injury to erythropoiesis, a stable increase in the number of bone marrow lymphocytes, a remote development of lymph node hypoplasia, and reduction of functional neutrophil and lymphocyte pools.     

Structural chromosomal damages in myelokaryocytes exposed to plutonium-239 dioxide

Plutonium 239 dioxide, with particle sizes of 1-2 micron, injected to Wistar rats intravenously in doses of 92.5, 46.3, and 23.2 kBq/kg body mass, increased the frequency of chromosome aberrations in myelokaryocytes by 3.7, 2.3 and 1.7 times, respectively, compared to spontaneous levels.     

Factors affecting the mobility of plutonium-238 dioxide in the rat.

A major factor influencing the movement of plutonium-238 from the lungs to blood after the intubation of oxide suspensions is the presense of 0.001 micrometer diameter particles. In a polydisperse suspension of particles this fraction increases with time, due it is thought, to fragmentation of larger particles induced by alpha decay. The rate of this process could account for the greater transportability in vivo of plutonium-238 relative to plutonium-239 when the oxides are inhaled. In blood, 0.001 micrometer diameter plutonium-238 oxide particles undergo a rapid reaction to form a low molecular weight species before plutonium is complexed with transferrin and citrate ions. The filtration of this species through the kidneys may explain the observed enhanced urinary excretion of plutonium relative to administered plutonium citrate. The mechanism of urinary excretion and relationship between cumulative urinary excretion and body content for plutonium-238 is similar to that previously observed for plutonium-239, even though different methods of preparation of the oxides were used.     

The reactions of l nm particles of plutonium-238 dioxide and curium-244 dioxide with lung fluid

The reactions of 1 nm particles of plutonium-238 dioxide and curium-244 dioxide with rat lung fluid have been studied both in vitro and in vivo. The plutonium-238 particles are positively charged and combine by electrostatic attraction with the negative pulmonary surfactant which mediates the transfer of radioactivity to the blood. In contrast the curium-244 particles are negative and are assumed to diffuse passively through the alveolar walls. The results emphasise that electrostatic charge is an important factor governing the reaction of 1 nm actinide oxide particles with macromolecules.     

The association of inbreeding with lung fibrosis incidence in Beagle dogs that inhaled 238PuO2 or 239PuO2

Studies of health effects in animals after exposure to internally deposited radionuclides were intended to supplement observational studies in humans. Both nuclear workers and Beagle dogs have exhibited plutonium-associated lung fibrosis; however, the dogs' smaller gene pool may limit the applicability of findings to humans. Data on Beagles that inhaled either plutonium-238 dioxide ((238)PuO(2)) or plutonium-239 dioxide ((239)PuO(2)) were analyzed. Wright's Coefficient of Inbreeding was used to measure genetic or familial susceptibility and was assessed as an explanatory variable when modeling the association between lung fibrosis incidence and plutonium exposure. Lung fibrosis was diagnosed in approximately 80% of the exposed dogs compared with 23.7% of the control dogs. The maximum degree of inbreeding was 9.4%. Regardless of isotope, the addition of inbreeding significantly improved the model in female dogs but not in males. In female dogs, an increased inbreeding coefficient predicted decreased hazard of a lung fibrosis diagnosis. Lung fibrosis was common in these dogs with inbreeding affecting models of lung fibrosis incidence in females but not in males. The apparent protective effect in females predicted by these models of lung fibrosis incidence is likely to be minimal given the small degree of inbreeding in these groups.     

The reactions of 1.0 nanometre diameter plutonium-238 dioxide particles with rat lung fluid.

The reactions of 1.0 nm particles of plutonium-238 dioxide with rat lung fluid have been studied both in vivo and in vitro. In both cases two products have been identified, (i) plutonium-labelled pulmonary surfactant and (ii) a heterogeneous plutonium-labelled material isolated by column chromatography. The formation of plutonium-labelled pulmonary surfactant results in the rapid translocation of plutonium from lungs to blood and in a high urinary excretion relative to administered plutonium citrate.     

Biological action of plutonium-239 on Salmonella typhimurium

Salmonella typhimurium cells were exposed in a 239Pu citrate solution. Cell death and induction of gene mutations were an exponential function of gamma radiation dose. LD37 was 34.8 Gy; mutation doubling dose, 19 Gy.     

Effect of liposome-encapsulated pentacin on plutonium-239 excretion

A study was made of the influence of pentacin, encapsulated in liposomes, on the excretion of monomeric plutonium-239 from dogs and albino rats. Pentacin in a liposomal form, in comparison with free pentacin, increased the excretion of plutonium in urine from a dog body by 23.5% when administered in 24 h, and by 28% when administered in 20 days; in rats, the excretion increase made 40% after the administration in 30 or 45 days.     

Absorbed doses and hematological shifts in dogs inhaling submicron 239Pu dioxide

In dogs breathing submicron 239Pu dioxide, the absorbed doses were determined in 12 organs and tissues where the radionuclide was deposited; the integral doses to a whole body were also determined by the sum of the exposed organs. The relationship of the hematologic changes not only with the doses for "critical" tissues but also with the integral dose was studied.     

Determination of the plutonium-239 content of the body

In order to increase the informativeness of the indirect dosimetric estimates of plutonium-239 body levels complex makers are widely used to enhance natural excretion of the radionuclide in urine, the ratio between 239Pu levels in urine and skeleton being measured. However, as the onset of chelate application is postponed its efficacy, with respect to the skeleton, sharply decreases making it impossible to obtain reliable information concerning plutonium 239 levels in bone tissues at later times.     

Cytogenetic effects of extremely low doses of plutonium-238 alpha-particle irradiation in CHO K-1 cells

CHO K-1 cells were irradiated during the G1 phase with 0.5-6 rad of alpha particles. There was no appreciable cell killing in this low dose range. Significantly increased frequencies of sister-chromatid exchanges were induced by doses as low as 0.5 rad of alpha-particle irradiation, whereas increased numbers of chromosomal aberrations were observed following exposure to 2 rad. These results suggest that very low doses of alpha radiation may lead to radiation-induced genetic alterations.     

Early endosteal bone response to incorporated plutonium-238 in mice

Ten Swiss albino ICR SPF female mice 110 days old (weight about 30 g) were exposed for 48 hours to a solution of plutonium-238 nitrate (spec. act. 5 MBq/1 m1, pH 2.7) injected in amounts of 0.01 ml into the popliteal area of the right femur, each thus receiving about 500 kBq per 30 g body weight. Of the injected activity, 50% was retained in the right femur, 2% in the left femur and approximately 2-3% in the excrements collected separately from each animal during the whole exposure period. Ultrastructurally, electron micrographs revealed a variety of changes, including hypertrophy and destruction of endosteal cell organelles (primary damage), deformation and hypertrophy of osteocytes (secondary damage) and the irregularities in the osteocyte self-burial process leading to an abnormal formation of bone tissue structure (tertiary damage). Qualitatively, these changes in the irradiated bone ultrastructure were analogous to those occurring with age. This was confirmed by comparing two groups of control mice 110 and 330 days old. Assessed quantitatively, changes due to irradiation were more pronounced than those associated with aging.     

Expression of transforming growth factor alpha in plutonium-239-induced lung neoplasms in dogs: investigations of autocrine mechanisms of growth

We have previously shown that 47% of radiation-induced lung neoplasms in dogs exhibit increased expression of epidermal growth factor receptor (EGFR). In this study, we investigated the expression of transforming growth factor alpha (TGF-alpha), a ligand for EGFR, to determine if an autocrine mechanism for growth stimulation was present in these tumors. As determined by immunohistochemistry, 59% (26/44) of the lung neoplasms examined had increased expression of TGF-alpha. Expression of TGF-alpha was not related to the etiology of the tumor, e.g., spontaneous or plutonium-induced; however, it was related to the phenotype of the tumor. Statistical analysis of the correlation of EGFR and TGF-alpha expression within the same tumor did not show a positive association; however, specific phenotypes did have statistically significant expression of EGFR or TGF-alpha, suggesting that overexpression of either the ligand or its receptor conferred a growth advantage to the neoplasm. Twenty-seven percent (32/117) of radiation-induced proliferative epithelial foci expressed TGF-alpha, and a portion of those foci (8/32) expressed both EGFR and TGF-alpha. This supports the hypothesis that these foci represent preneoplastic lesions, and suggests that those foci exhibiting increased expression of the growth factor or its receptor are at greater risk for progressing to neoplasia.     

Longevity of animals in combined exposure to total gamma irradiation and incorporated plutonium-239

The paper presents the functions and nomograms permitting to estimate the expected consequences of the combined effect of alpha-radiation from incorporated plutonium 239 and external gamma-rays at random doses on the lifetime of animals.