The applicability of the concept of morpho-physiologic metabolic factors to the modification of the distribution of 239Pu deposited in the respiratory organs

At the stage of intensive resorption of plutonium from lungs to blood the competitive per os administration of an iron preparation increased plutonium excretion from blood. As a result, soft tissues were enriched with plutonium at an early stage of metabolism. However, at the end of the experiment (30 days) the radionuclide content of soft tissues dropped to control values. Simultaneously, the share of plutonium deposited in bone tissue decreased considerably and that of the radionuclide eliminated from the body increased throughout the entire period of observation.     

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.     

Plutonium(III) complexation by humic substances studied by X-ray absorption fine structure spectroscopy

We determined structural parameters for the near-neighbor surrounding of plutonium(III) in complexes with humic and fulvic acids at pH 1 and for the purpose of comparison also for the plutonium(III) aquo ion by means of X-ray absorption fine structure (XAFS) spectroscopy. It could be shown that in the complexes with humic substances as well as in the plutonium(III) aquo ion sample the trivalent oxidation state of plutonium was stable within the time of the experiment. In the humate and fulvate complexes, the plutonium(III) is surrounded by about eight oxygen atoms with an average Pu–O distance of 2.48 ± 0.02 Å. The structural parameters determined for plutonium(III)–humate and –fulvate complexes were compared to structural parameters of plutonium(III) and plutonium(IV) aquo ions.     

In vitro and in vivo assessment of plutonium speciation and decorporation in blood and target retention tissues after a systemic contamination followed by an early treatment with DTPA

This study identifies the main sources of systemic plutonium decorporated in the rat after DTPA i.v. at the dose recommended for humans (30 mumol kg(-1)). For this purpose, standard biokinetic approaches are combined to plasma ultrafiltration for separation of plutonium complexes according to their molecular weight. In vitro studies show that at the recommended DTPA dose, less than 5% of the plasma plutonium of contaminated rats can be displaced from high-molecular-weight ligands. After i.v. administration of Pu-DTPA, early ultrafiltrability of plutonium in plasma decreases with total DTPA dose, which is associated with an increase in plutonium bone retention. This demonstrates the instability of Pu-DTPA complexes, injected in vivo, below the minimal Ca-DTPA dose of 30 mumol kg(-1). Plutonium biokinetics is compared in rats contaminated by plutonium-citrate i.v. and treated or not with DTPA after 1 h. No significant decrease in plasma plutonium is observed for the first hour after treatment, and the fraction of low-molecular-weight plutonium in plasma is nearly constant [5.4% compared with 90% in Pu-DTPA i.v. (30 mumol kg(-1)) and 0.7% in controls]. Thus plutonium decorporation by DTPA is a slow process that mainly involves retention compartments other than the blood. Plutonium-ligand complexes formed during plutonium deposition in the retention organs appear to be the main source of decorporated plutonium.     

Decorporation Approach Following Rat Lung Contamination with a Moderately Soluble Compound of Plutonium Using Local and Systemic Ca-DTPA Combined Chelation

Decorporation efficacy of prompt pulmonary delivery of DTPA dry powder was assessed following lung contamination with plutonium nitrate and compared to an intravenous injection of DTPA solution and a combined administration of both DTPA compounds. In addition, efficacy of a delayed treatment was assessed. In case of either early or late administration, insufflated DTPA was more efficient than intravenously injected DTPA in reducing the plutonium lung burden due to its high local concentration. Prompt treatment with DTPA powder was also more effective in limiting extrapulmonary deposits by removing the early transportable fraction of plutonium from lungs prior its absorption into blood. Translocation of DTPA from lungs to blood may also contribute to the decrease in extrapulmonary retention, as shown by reduced liver deposit after delayed pulmonary administration of DTPA. Efficacy of DTPA dry powder was further increased by the combined intravenous administration of DTPA solution for reducing extrapulmonary deposits of plutonium and promoting its urinary excretion. According to our results, the most effective treatment protocol for plutonium decorporation was the early pulmonary delivery of DTPA powder supplemented by an intravenous injection of DTPA solution. Following inhalation of plutonium as nitrate chemical form, this combined chelation therapy should provide a more effective method of treatment than conventional intravenous injection alone. At later stages following lung contamination, pulmonary administration of DTPA should also be considered as the treatment of choice for decreasing the lung burden.     

Experimental studies of the translocation of plutonium from simulated wound sites in the rat.

Wound contamination with plutonium was simulated in rats by injection into either muscle or subcutaneous tissue. The distribution after the injection of plutonium nitrate indicated that: (i) clearance from the contaminated tissue was due mainly to the movement of soluble complexes of plutonium, principally to the skeleton and liver, but also involved slower movement of polymerized, particulate plutonium to lymph nodes; (ii) clearance of soluble plutonium, and hence the overall state of clearance, was dependent on the tissue fluid flow through the contiminated tissue and the mass of plutonium deposited; (iii) lymphatic clearance of particulate plutonium resulted in the release of some particles into the circulation and subsequent uptake by the liver. Intramuscular deposition of small plutonium dioxide particles (approximately 1 nm in diameter) resulted in a greater rate of clearance of plutonium than deposition of the nitrate. Although the solubility of these particles was evident from the level of skeletal uptake of plutonium, a high level of excretion indicated that some plutonium was filtered into the urine in an undissolved form.     

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.     

A comparison of the distribution of 239-Pu and calcein in the illium of the female CBA mouse

Conclusions As a model for the behaviour of plutonium in bone, calcein data must be treated with some care. It does not label the same surfaces as plutonium which results in different distribution patterns at later times. However, it might be that if in man or a long lived animal, labelling occured over a period of weeks, so that most surfaces become labelled, the resultant distribution pattern at late times would more nearly model plutonium behaviour. The single biggest difference between the behaviour of the two substances is the build up of plutonium in the bone marrow, an effect seen only slightly with calcein. The other differences noted was the redeposition of plutonium, as a consequence of recycling of the radionuclide, maintaining a concentration of plutonium on endosteal surface.     

Past exposure to densely ionizing radiation leaves a unique permanent signature in the genome

Speculation has long surrounded the question of whether past exposure to ionizing radiation leaves a unique permanent signature in the genome. Intrachromosomal rearrangements or deletions are produced much more efficiently by densely ionizing radiation than by chemical mutagens, x-rays, or endogenous aging processes. Until recently, such stable intrachromosomal aberrations have been very hard to detect, but a new chromosome band painting technique has made their detection practical. We report the detection and quantification of stable intrachromosomal aberrations in lymphocytes of healthy former nuclear-weapons workers who were exposed to plutonium many years ago. Even many years after occupational exposure, more than half the blood cells of the healthy plutonium workers contain large (>6 Mb) intrachromosomal rearrangements. The yield of these aberrations was highly correlated with plutonium dose to the bone marrow. The control groups contained very few such intrachromosomal aberrations. Quantification of this large-scale chromosomal damage in human populations exposed many years earlier will lead to new insights into the mechanisms and risks of cytogenetic damage.     

Plutonium microdistribution in the lungs of Mayak workers

The degree of nonuniform distribution of plutonium in the human lung has not been determined; thus current dosimetric models do not account for nonuniform irradiation. A better scientific basis is needed for assessing the risk of developing radiation-induced disease from inhaled alpha-particle-emitting radionuclides. We measured the distribution of plutonium activity in the lung by autoradiography and related the activity to specific compartments of the lung. The study materials were lung specimens from deceased workers employed by the Mayak Production Association. The approach to analyzing these lung samples used contemporary stereological sampling and analysis techniques together with quantitative alpha-particle autoradiography. For the first time, plutonium distribution has been quantified in the human lung. The distribution of long-term retained plutonium is nonuniform, and a significant portion of plutonium was retained in pulmonary scars. In addition, a large fraction of plutonium was present in the parenchyma, where it was retained much longer than was estimated previously. The sequestration of plutonium particles in scars would greatly reduce the radiation exposure of the critical target cells and tissues for lung cancer. Thus the prolonged retention of plutonium in lung scars may not increase the dose or risk for lung cancer.     

Organic Constituents and Complexation of Nickel(II), Iron(III), Cadmium(II), and plutonium(IV) in Soybean Xylem Exudates

The xylem exudates of soybean (Glycine max cv Williams), provided with fixed N, were characterized as to their organic constituents and in vivo and in vitro complexation of plutonium, iron, cadmium, and nickel. Ion exchange fractionation of whole exudates into their compound classes (organic acid, neutral, amino acid, and polyphosphate), followed by thinlayer electrophoresis, permitted evaluation of the types of ligands which stabilize each element. The polyvalent elements plutonium(IV) and iron(III) are found primarily as organic acid complexes, while the divalent elements nickel(II) and cadmium(II) are associated primarily with components of the amino acid/peptide fraction. For plutonium and cadmium, it was not possible to fully duplicate complexes formed in vivo by back reaction with whole exudates or individual class fractions, indicating the possible importance of plant induction processes, reaction kinetics, and/or the formation of mixed ligand complexes. The number and distribution of specific iron- and nickel-containing complexes varies with plant age and appears to be related to the relative concentration of organic acids and amino acids/peptides being produced and transported in the xylem as the plant matures.     

Role of biocomponents of the bile and excreta in the elimination of plutonium and americium from the body

A study was made of the role of biocomponents of bile, urine and feces in the elimination of plutonium and americium from the organism. Plutonium 239 and americium 241 were separated in bile due to higher tropism of plutonium to low molecular weight ligands, and of americium, to a protein-containing fraction. The status of plutonium excreted in feces was the same as the physicochemical status of americium. Plutonium 239 and americium 241 eliminated in urine were in a completely ultrafiltered state.     

The loss of transportable plutonium deposits from the macrophages of the rat femoral bone marrow

Conclusion The results showed that plutonium may be retained in bone marrow macrophages for a considerable time. Consequently, plutonium deposits in these cells may substantially irradiate components of the surrounding bone marrow and cells on bone surfaces. In red bone marrow these include the radiation sensitive cells which give rise to leukaemia. If follows that bone marrow deposits of plutonium resulting from the turnover of contaminated bone are likely to be important in radiation protection dosimetry. The period of plutonium retention in the bone marrow was found to exceed that in the liver.In addition to the above the results of this study suggest that the autoradiographic methods used to measure the plutonium content of the bone marrow are likely to be suitable for studying those factors which may affect the rate of loss of alpha-emitters from this tissue. These factors include the iron status, sex, and age of the animal and effects of drugs and radiation on the cells.     

Distribution of plutonium in the body of rats after its intratracheal administration in the form of a Pu(IV)-TBP complex

Tributyl phosphate intratracheally administered to rat body with a Pu(IV)-TBP complex does not increase the accumulation of plutonium in the skeleton and liver. Plutonium is excreted from the lungs more readily than Pu(IV) nitrate and its large amounts are resorbed in the blood early after the administration; its excretion in feces is approximately 100 times more intense than in urine.     

The specificity of the deposition of intratracheally administered plutonium in different skeletal bones with a change in iron homeostasis]

A study was made of the distribution of plutonium-239 injected intratracheally within different bones of the skeleton, the iron status in the blood being changed. The iron preparation caused a 2.5-3-fold decrease in the plutonium loading onto cancellous bone tissue that displayed, in ordinary conditions, a higher tropism to the radionuclide than a cortical highly mineralized bone did.     

The uptake and redistribution of 241pu within the gonads.

Male and female hamsters and a female rabbit were injected with 241Pu citrate. The hamsters were killed serially at 15 min, 2 hours, 1 day and 10 days after injection, and the rabbit 1 week after injection. The gonads were examined for 241Pu by tissue-section autoradiography. Soon after injection the plutonium was concentrated by the contents of atretic Graafian follicles and by thecal rings in the ovary, but was found to be dispersed throughout the testes. It is suggested that the disperse distribution in the testes which is only seen soon after injection may be an artefact of tissue processing. One day after injection, plutonium was accumulated by macrophages in both the follicles of the ovary and in the interstitial tissue of the testes. Macrophages containing plutonium later migrated away from the aretic ovarian follicles towards the ovarian medulla. This pattern of distribution and redistribution in the ovary is regarded as likely to lower the effective dose from a-emitting plutonium isotopes to the viable oocytes. No migration of macrophages was seen in the testes. Histochemical staining methods revealed the presence of acid protoglycans, including chondroitin sulphate, and glycoproteins at the sites of plutonium concentration in the ovary. These molecules are regarded as likely receptor sites for plutonium. In the testes no acidic carbohydrates were found, and it is suggested that the initial binding site for plutonium may be a compound lipid. This was deduced from the apparent inability of the interstitial tissue of the testes to bind plutonium in situ.     

Differences in the uptake of transferrin bound 239Pu and 59Fe into multicellular spheroids of hepatocytes from adult male rats

Hepatocytes were cultured as monolayers and multicellular spheroids, respectively. The uptake of both transferrin-bound metals, iron and plutonium, differed significantly between these two culture systems. The uptake into the multicellular spheroids for plutonium was about 30 times greater, and for iron about 4 times greater, than in monolayer-cultured hepatocytes, which is not a consequence of proliferation and/or de-differentiation of the hepatocytes in the multicellular spheroid culture system. A comparison of the iron and plutonium uptake showed that plutonium was delivered to the cells to an 8-fold greater extent than iron if the hepatocytes were cultured as spheroids. Additionally, the binding of plutonium was not inhibited by preincubation of the spheroids with the iron-transferrin complex. Therefore, we propose that there are two different binding sites for iron and plutonium on hepatocyte membranes.     

Characteristics of the cohort of workers at the Mayak nuclear complex.

At Branch No. 1 of the Russian State Research Center "Biophysics Institute", a registry has been created of workers at the "Mayak" Production Association, the first nuclear complex in Russia. This registry includes 18,830 persons hired at Mayak's nuclear reactors and radiochemical and plutonium production plant between 1948 and 1972. Twenty-five percent of these workers are women. As of December 31, 1994, the vital status is known for approximately 90% of the cohort members. A total of 5,118 persons have died. The cause for 97% of total deaths has been ascertained. The cohort members were exposed to both external gamma radiation and internal radiation from incorporated plutonium. The plutonium body burden has been measured in 30% of the cohort members with potential for plutonium exposure. External gamma-ray doses were in the range from tenths of milligrays to about 10 Gy, and plutonium body burdens were up to about 260 kBq. In view of the nature of the Mayak worker cohort, it has the potential to provide reasonably precise, quantitative estimates of the long-term health effects associated with chronic low-dose-rate exposure to external gamma radiation as well as internal radiation from plutonium. However, a number of issues must be addressed before credible risk estimates can be obtained from this cohort. These issues include the development of an appropriate internal comparison group and/or external rates and separating of the effects of internal and external exposures on risk estimates.     

Methodology Using a Portable X-Ray Fluorescence Device for On-Site and Rapid Evaluation of Heavy-Atom Contamination in Wounds: A Model Study for Application to Plutonium Contamination

Workers decommissioning the Fukushima-Daiichi nuclear power plant damaged from the Great East Japan Earthquake and resulting tsunami are at risk of injury with possible contamination from radioactive heavy atoms including actinides, such as plutonium. We propose a new methodology for on-site and rapid evaluation of heavy-atom contamination in wounds using a portable X-ray fluorescence (XRF) device. In the present study, stable lead was used as the model contaminant substitute for radioactive heavy atoms. First, the wound model was developed by placing a liquid blood phantom on an epoxy resin wound phantom contaminated with lead. Next, the correlation between the concentration of contaminant and the XRF peak intensity was formulated considering the thickness of blood exiting the wound. Methods to determine the minimum detection limit (MDL) of contaminants at any maximal equivalent dose to the wound by XRF measurement were also established. For example, in this system, at a maximal equivalent dose of 16.5 mSv to the wound and blood thickness of 0.5 mm, the MDL value for lead was 1.2 ppm (3.1 nmol). The radioactivity of ²³⁹Pu corresponding to 3.1 nmol is 1.7 kBq, which is lower than the radioactivity of ²³⁹Pu contaminating puncture wounds in previous severe accidents. In conclusion, the established methodology could be beneficial for future development of a method to evaluate plutonium contamination in wounds. Highlights: Methodology for evaluation of heavy-atom contamination in a wound was established. A portable X-ray fluorescence device enables on-site, rapid and direct evaluation. This method is expected to be used for evaluation of plutonium contamination in wounds.     

Stable intrachromosomal biomarkers of past exposure to densely ionizing radiation in several chromosomes of exposed individuals

A multicolor banding (mBAND) fluorescence in situ hybridization technique was used to investigate the presence inhuman populations of a stable biomarker-intrachromosomal chromosome aberrations-of past exposure to high-LET radiation. Peripheral blood lymphocytes were taken from healthy Russian nuclear workers occupationally exposed from 1949 onward to either plutonium, gamma rays or both. Metaphase spreads were produced and chromosomes 1 and 2 were hybridized with mBAND FISH probes and scored for intra-chromosomal aberrations. A large yield of intrachromosomal aberrations was observed in both chromosomes of the individuals exposed to high doses of plutonium, whereas there was no significant increase over the (low) background control rate in the population who were exposed to high doses of gamma rays.Interchromosome aberration yields were similar in both the high plutonium and the high gamma-ray groups. These results for chromosome 1 and 2 confirm and extend data published previously for chromosome 5. Intrachromosomal aberrations thus represent a potential biomarker for past exposure to high-LET radiations such as alpha particles and neutrons and could possibly be used as a biodosimeter to estimate both the dose and type of radiation exposure in previously exposed populations.