Self-renewal capacity of murine hemopoietic stem cells under internal contamination with239Pu and241Am

Summary The self-renewal capacity of murine pluripotent hemopoietic stem cells (CFU-S) of vertebral bone marrow was studied under conditions of short-term and long-term internal contamination with²³⁹Pu or²⁴¹Am in female mice. Measurement of the CFU-S self-renewal capacity was carried out using double transplantation assay. To evaluate the production of differentiated progeny of stem cells average erythroblast numbers/visible spleen colony and⁵⁹Fe-uptake/colony were computed. The marrow cellularity/vertebra and the number of CFU-S/vertebra were decreased and affected more by²³⁹Pu than by²⁴¹Am. The production of erythroblasts per a single CFU-S and the⁵⁹Fe-uptake/colony were reduced, similarly the numbers of secondary spleen colonies and of secondary CFU-S in primary colonies. The above changes resulting from impaired functions of surviving CFU-S were more serious with²⁴¹Am than with²³⁹Pu. The biological effects of plutonium and americium appeared independent of the phase of contamination.     

Long-term effects of low-level 239Pu contamination on murine bone-marrow stem cells and their progeny

The effects of long-term internal contamination with 13.3 kBq kg-1 239Pu injected intravenously were studied in 10-week-old ICR (SPF) female mice. Radiosensitivity of spleen colony-forming units (CFU-S) and 125IUdR incorporating into proliferating cells of vertebral bone marrow and spleens were determined in plutonium-treated and control animals one year after nuclide injection. The CFU-S in 239Pu-treated mice were more sensitive to X-rays (D0 = 0.52 +/- 0.01 Gy) than in controls (D0 = 0.84 +/- 0.02 Gy). 125IUdR incorporation into bone marrow and spleen cells was reduced after plutonium contamination. At one year following plutonium injection, the occurrence of chromosome aberrations was evaluated in metaphase figures of femoral bone marrow cells. The frequency of aberrations increased early after plutonium treatment, at later intervals it tended to decrease but not below the control level. While the relative numbers of vertebral marrow CFU-S decreased significantly, but only to 86 per cent of normal, cellularity of vertebral bone marrow, peripheral blood counts and survival of 239Pu-treated mice did not differ from the control data.     

Radiosensitivity of vertebral bone marrow CFU-S surviving in mice internally contaminated with239Pu or241Am

Summary The radiosensitivity of pluripotent hemopoietic stem cells was studied in ICR Swiss mice (28 g/mouse) given i.v. 198.6 kBq²³⁹Pu/kg as citrate complex or 208.6 kBq²⁴¹Am/kg as nitrate at the age of 10 weeks. The bone marrow cells were examined at the early and late phases of radionuclide contamination. To obtain data for survival curves andD ₀ of stem cells the CFU-S assay was used and the donor vertebral marrow cells were exposed to the complementary X-irradiation either early after injection to the heavily irradiated recipients or to the in vitro irradiation given before the transplantation. To determine the iron uptake in splenic erythroid progeny the recipients given marrow cells unexposed to the X-rays received 37 kBq⁵⁹Fe 6 h before they were killed and the relative activity per colony was calculated. The radiation effect of the used actinides on the bone marrow cells resulted in decreased cellularity and seriously altered both relative and absolute CFU-S numbers. The radiosensitivity of CFU-S increased in all intervals examined (D ₀ from 0.60 to 0.86 Gy, in controls 0.97 to 1.06 Gy) and was more expressed when the CFU-S were exposed to the X-rays immediately after the bone marrow cell transplantation to the heavily irradiated hosts. The stem cell pool appeared, especially at older age, to be affected also in its ability to produce erythrocytic progeny.     

Aminotransferase and lactate dehydrogenase activity in the blood of dogs exposed to the joint action of external gamma- and internal alpha-radiation

After the effect of external gamma-radiation (6.5 to 51.6 mC/kg) and inhaled 239Pu submicron oxide, containing 25% of 241Am, (approximately 7 to 10 kBq/kg) delivered separately and in a combination, activities of alanine-aspartate aminotransferase and lactate dehydrogenase changed in an undulatory manner tending to increase at later times; the change rating was a function of type and level of radiation as well as the time lapsed from the onset of exposure. The combined effect of gamma- and alpha-radiation did not exceed the additive effect of the two factors delivered separately.     

Effect of inhaled alpha-emitting nuclides on mouse alveolar macrophages

The effects of inhaled alpha emitters on the free cell population of the mouse lung were investigated up to 100 days after exposure. Groups of mice inhaled aerosols of 238PuO2, 239PuO2, or 241Am(NO3)3 to give alveolar deposits resulting in lung-averaged cumulative absorbed doses of about 20 Gy by the end of the study. Initially, with 238Pu most of the activity was associated with relatively few pulmonary alveolar macrophages (PAM), whereas with 241Am, all pulmonary alveolar macrophages were labeled and a substantial fraction was extracellular. The free cell population of the lung was sampled using bronchoalveolar lavage. The main parameters investigated were (a) the recovery and total numbers of free cells, including PAM, lymphocytes, and neutrophils; (b) the incidence of nuclear abnormalities in PAM (cells with more than one nucleus or with micronuclei); and (c) metabolic activation of PAM from measurements of their size and associated beta-glucuronidase activity. All three actinides produced depletions in total numbers of PAM, increased incidences of nuclear abnormalities, and metabolic activation of PAM, without a marked infiltration of inflammatory cells. Americium-241, which is distributed relatively uniformly in PAM, produced the most marked changes in that population and 238Pu, which gave the most inhomogeneous distribution of activity, produced the least.     

Removal of Pu and am from beagles and mice by 3,4,3-LICAM(C) or 3,4,3-LICAM(S)

Decorporation of Pu and Am by tetrameric catechoylamide (CAM) ligands has been investigated in beagles and mice. Eight dogs were injected intravenously (iv) with 237 + 239Pu(IV) + 241Am(III) citrate, and 30 min later, pairs of dogs were injected iv with 30 mumole/kg of 3,4,3-LICAM(C) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-5-sulfobenzoyl)tetr aazatetradecane, tetrasodium salt], 3,4,3-LICAM(S) [N1,N5,N10,N14-tetrakis(2,3-dihydroxy-4-carboxybenzoyl)te traazatetradecane, tetrasodium salt], CaNa3-DTPA, or each of the latter two ligands. Blood was sampled, and excreta were collected for 7 days, at which time the dogs were sacrificed and nuclide retention in liver and nonliver tissue was measured. Groups of five mice were each given 238Pu(IV) or 241Am(III) citrate iv; 3 min later 30 mumole/kg of a CAM ligand was injected intraperitoneally, mice were killed at 24 hr, and separated excreta and tissues were analyzed. In the dogs, average retention at 7 days of the injected Pu and Am, respectively, was as follows: 12 and 70% after treatment with a CAM ligand alone; 30 and 20% after DTPA; 12 and 20% after LICAM(S) plus DTPA; 90 and 89% without a ligand. In the mice, mean retention of the injected Pu and Am, respectively, was as follows: 14 and 66% after treatment with LICAM(C); 21 and 54% after LICAM(S); 91 and 87% without a ligand. In both species, about 99% of net Pu excretion (excretion with ligand - excretion without ligand) promoted in 24 hr by DTPA or LICAM(S) was in the urine, whereas about 10% of net Pu excretion promoted by the less hydrophilic LICAM(C) was in feces. Delayed excretion of both Am and Pu was significant in all ligand-treated dogs. Comparison of the nuclide content of tissues of ligand-treated mice with those of mice killed 3 min after nuclide injection indicated that the CAM ligands chelated circulating Pu and Am and prevented further deposition. In addition, the CAM ligands removed much of the presumably loosely bound Pu present in liver and skeleton at the time of ligand injection. LICAM(C) was more effective in removing Pu from liver and LICAM(S) was more effective in the skeleton. Moderate to severe uremia and histological evidence of cell killing in the distal tubules of the kidney were observed in the four dogs injected once with 30 mumole/kg of LICAM(S).(ABSTRACT TRUNCATED AT 400 WORDS)     

Estimation of rate constant for dissolution of radioactive fuel particles

Some theoretical of the experimental investigation of solubility of radioactive aerosols were examined. Filters, which were exposed during October-November 1987 in Pripyat town, were studied. Measurements on 22 November 1987 showed that an activity in the air was 12.1-20.8 mBq/m3 for 137Cs, 34.9-89.3 mBq/m-3 for 144Ce, 24.3-30.5 mBq/m-3 for 106Ru. Disperse structure of aerosol hot particles and the number of hot particles on each filter fragment was estimated by radiography. To determine a dissolution rate constant a static system with two 0.14 micron pore size membrane MFE filters (Dubna, Russia) enclosing fragments of Petryanov filters was selected. The composition was held in Gamble's solution lung fluid anf then in 0.1 mol/l HCl as dastic juice simulation. The activity of 90Sr, 238Pu, 239 + 240Pu, 241Am and 244Cm in aerosol filters and solutions was measured by radiochemical methods. It was shown that leaching of radionuclides from aerosol hot particles in lung fluid simulation decreases in line 137Cs > 90Sr > 239 + 240Pu > or = 241Am, depending om particle diameter and time. Dissolution constants were presented. Dissolution of aerosol particles in 0.1 mol/l HCl is also shown (dissolution time was 3 days). A radionuclide transition to HCl solution decreases in line 90Am 241Am > 137Cs > 239 + 240Pu. A transition degree reached 21% for 90Sr and extraction of 241Am was 3-17%.     

A comparison of the natural survival of beagle dogs injected intravenously with low levels of 239Pu, 226Ra, 228Ra, 228Th, or 90Sr

The natural survival, relative to properly chosen controls, of 26 beagle dogs injected once intravenously with an average of 0.58 +/- 0.04 kBq 239Pu/kg, 23 dogs injected with 2.31 +/- 0.43 kBq 226Ra/kg, 13 dogs injected with 1.84 +/- 0.26 kBq 228Ra/kg, 12 dogs injected with 0.56 +/- 0.030 kBq 228Th/kg, and 12 dogs injected with 21.13 +/- 1.74 kBq 90Sr/kg was evaluated statistically. The amounts of these radionuclides are related directly to the estimated maximum permissible body burdens for humans suggested in ICRP II (1959). They constitute a level of exposure that initially was assumed to cause no deleterious effects in dogs. This study had two objectives: (1) identification of homogeneous control groups against which to evaluate the survival of the irradiated groups and (2) comparison of the survival characteristics and estimation of mortality or hazard rate ratios for control dogs vs dogs injected with the baseline dosages given above. It was shown, by goodness-of-fit plots, that the Cox proportional hazards model was an appropriate method of analysis. Therefore, covariates that possibly could influence survival were tested for significance. Only the effects of grand mal seizure, which is caused in epileptic dogs by an external stimulus and can be fatal if untreated, were significant (P less than 0.0001). Consequently, in the final model, death from grand mal seizure was considered as accidental. After censoring the dogs dying from grand mal seizure, it was established that the data for the control groups from previous and contemporary experiments could be pooled. The change in hazard rates relative to controls resulting from exposure to the baseline radionuclide level was modest, 1.6 times for 239Pu (P = 0.033), 1.0(4) for 226Ra (P = 0.86), 1.9 for 228Ra (P = 0.035), 2.5 for 228Th (P less than 0.001), and 0.52 for 90Sr (P = 0.041). Bone tumor induction was clearly elevated in dogs injected with 239Pu and 228Th. When the effect of these bone tumors on survival was removed by censoring, the dogs injected with 239Pu were indistinguishable from the controls. In contrast, the effects of bone tumor on group survival of the 228Ra and 228Th dogs were not significant. Thus, no additional life-shortening effects beyond those attributable to bone tumor were suggested by these data for 239Pu, but other, as yet unspecified, confounders are suggested for 228Ra and 228Th.     

骨髓基质细胞的辐射效应及其临床意义

小鼠骨髓基质细胞团在γ线照射后的Do值为2.40Gy,但其成灶能力损伤后持续时间较久。正常骨髓基质细胞能促进骨髓GM-CFU-C的生长;照射10-80Gy后的骨髓基质细胞失去这种促进作用。文中讨论了骨髓基质细胞的辐射效应及其临床意义,提出了谨慎选择放射治疗剂量的必要性。     

Microdistribution and localized dosimetry of 241Am in bones of beagle dogs

The microdistribution of 241Am in selected bones of seven beagle dogs was analysed using a computer controlled microscope photometer. Four of the animals receiving between 102.5 and 165 kBq/kg were killed between 7 and 20 days after injection, and three animals receiving 32.9-34.0 kBq/kg were killed between 1300 and 1569 days. Using the photometric scanning technique, the concentrations of 241Am in several anatomical regions, as well as the specific surface activities and their variations, dose rates, accumulated radiation doses, burial depths and morphometric parameters, were derived. Dose rates to the 0-10 micron marrow band adjacent to surfaces were found to be between 8.6 and 15.7 times higher than the average skeletal dose. Accumulated radiation doses from initial deposits to lining cells were estimated to be between 87 and 252 Gy. The average burial depth in the animals killed at later times was around 8 micron. Morphometric parameters showed that radiation damage occurred in these animals, resulting in abnormal trabecular architecture. A positive correlation between specific surface activity and local turnover rates was established.     

Functional state of the thyroid gland in sheep at a remote period after single administration of Sr-90, Pu-239 and their mixture

Five years after single intravenous injection of a mixture of 239Pu and 90Sr to semifine-wool sheep (7.4 kBq/kg + 185 kBq/kg) the iodine-fixing and hormone secreting functions of the thyroid gland were inhibited; where 90Sr alone was injected in the above dose inhibited was the hormone-secreting function only. Since 239Pu alone did not cause such alterations, the observed remote effect was attributed to the effect of the incorporated 90Sr.     

Comparative studies on the lysosomal association of monomeric 239Pu and 241Am in rat and Chinese hamster liver: analysis with sucrose, metrizamide, and Percoll density gradients of subcellular binding as dependent on time

The binding of 239Pu and 241Am in the livers of Chinese hamsters and rats was analyzed by centrifugation of a mitochondrial-lysosomal fraction in sucrose, metrizamide, and Percoll density gradients at intervals between 4 and 70 days after nuclide injection. The behavior of 239Pu and 241Am during the centrifugation experiments was very similar. In contrast to the results for rats, the median densities of the nuclide profiles from hamsters decrease with time in hyperosmolar sucrose gradients, as does the nuclide fraction liberated by addition of Triton X-100, and the nuclide profiles do not respond typically to Triton WR 1339 treatment of the animals. The results with nearly iso- osmolar metrizamide gradients, together with those for Percoll, agree with the assumption that there is an initial lysosomal association of the transuranium elements. It was concluded from the results that the major fraction of 239Pu and 241Am remained bound to typical lysosomes in rat liver, whereas those in hamster liver may be transformed into telolysosomes . Possibly, a vesicular biliary transport system for certain heavy metals, for which evidence exists in rat liver, does not occur in Chinese hamster liver.     

Plutonium,241Am,90sr,and137cs concentrations in some antarctic matrices

A radioecological survey in Antarctica shows that the^239+240Pu,²³⁸Pu,²⁴¹Am,⁹⁰Sr, and¹³⁷Cs activities were detectable in nearly all the samples. The activity level of^239+240Pu,²⁴¹Am, and¹³⁷Cs in antarctic sediments was about 5–20 times lower than in the northern Adriatic Sea sediments, but the²³⁸Pu activities were relatively high. It was interesting to note that the⁹⁰Sr concentrations in all the sediments tended to be low, which could be the result of the easier exchangeable behavior of⁹⁰Sr in water. High concentrations were detected in mosses and lichens and their activity levels were comparable to those in central Italy. The radionuclide ratio analyses show that the major part of^239+240Pu,²⁴¹Am,⁹⁰Sr, and¹³⁷Cs was a result of nuclear weapon tests. The higher²⁴¹Am/^239+240Pu ratio was observed and it could perhaps be the result of fallout of nuclear weapon tests prior to 1962. The²³⁸Pu/^239+240Pu ratio in the antarctic matrices was about seven times higher than in the Northern hemisphere and it could be inferred that the major part of²³⁸Pu was originating from the SNAP-9A satellite accident.     

243,244Cm studies in C57BL/Do mice

Three groups of C57BL/Do mice were injected with different activities of 243,244Cm so that the long-term biological effects could be evaluated. The biological retention, R, of injected curium in the skeleton at t days after injection could be represented by the equations R = 0.245e-0.000379t and R = 0.208e-0.000494t for male and female mice, respectively. Effective skeletal retention equations were used to calculate the cumulative mean skeletal dose in rad at 140 days before death in each group of mice. The primary objective of this study was to determine the relative biological effectiveness (RBE) of 243,244Cm compared to 226Ra, using bone sarcoma induction as the end point. Combined data (bone sarcomas per 10(6) mouse-rad) for male and female mice permitted the RBE value +/- SD for 243,244Cm to be calculated as 4.4 +/- 1.8 compared to 1.0 for 226Ra. A comparison of RBE values form a previous study in this mouse strain and the value for 243,244Cm from this study suggests that the trivalent actinides 241Am, 243,244Cm, and 249Cf are about three times less effective for bone sarcoma induction than 239Pu.     

Biosorption of radionuclides by Rhizopus arrhizus

The sorption of various radionuclides viz. 233U, 239Pu, 241Am, 144Ce, 147Pm, 152+154Eu and 95Zr from aqueous nitrate medium has been studied using biomass Rhizopus arrhizus. The biosorption of 233U and 239Pu was found to be maximum at pH 6-7 whereas for other trivalent actinides and fission products viz. 241Am, 144Ce, 147Pm, 152+154Eu and tetravalent 95Zr, it was more effective at pH 2. This biomass is a promising sorbant for the treatment of radioactive effluents from nuclear industry. © Rapid Science Ltd. 1998     

Influence of clay mineral type and organic matter content on the uptake of239Pu and241Am by plants

Summary The uptake of²³⁹Pu and²⁴¹Am from different clay mineral-organic matter-sand mixtures simulating contrasting soil types was examined in growth chamber experiments. The mixtures represented various combinations of organic matter (0, 5 and 10%), kaolinite (11 type) and montomorillonite (21 type) clay minerals, each at the levels of 5, 10 and 25%, and purified quartz sand (as filler).Results indicated a marked reduction in uptake of both²³⁹Pu and²⁴¹Am with increase in organic matter as well as clay content of the mixtures. The Pu Concentration Ratios (CRs) ranged from (2.5–7.0)×10^–3 in the case of kaolinite-organic matter mixtures, and from (0.9–5.5)×10^–3 in the case of montmorillonite-organic matter mixtures. The corresponding values of Am Concentration Ratios (CRs) obtained were (1.9–725.4)×10^–3 in the case of kaolinite-organic matter mixtures, and between (0.7–3.5)×10^–3 for the montmorillonite-organic matter mixtures.Reduction in the uptake of²⁴¹Am with increasing clay content was more pronounced in the montmorillonite clay-organic matter mixtures as compared to that in the case of kaolinite-organic matter mixtures. While similar qualitative reduction in²³⁹Pu CRs with increasing clay content was observed, the reduction was less marked than in the case of²⁴¹Am. The values for Am CRs were higher than the corresponding Pu CRs in kaolinite based mixtures whereas in the case of montmorillonite-organic matter mixtures Pu CRs exceeded the Am CRs.Increasing organic matter content and its interaction with both kaolinite and montmorillonite clay minerals were found to be equally effective in reducing the uptake of²³⁹Pu as well as²⁴¹Am by plants.     

Effective and non-effective levels of the inhalation action of transuranium radionuclides estimated by changes in the parameters of cardiac mass in dogs

Effective and noneffective levels of inhalation of 239Pu and 241Am transuranium radionuclides were estimated by changes in heart mass parameters of 143 mongrel dogs.     

Organic forms of artificial radionuclide compounds in soil solutions from natural biogeocenosis

The date on the distribution of the main radiologicaly important polutants of biosphera (90Sr, 137Cs, 239 + 240Pu, 238Pu, 241Am) over the molecular mass fractions of organic matter in the soil solutions of natural environments are presented. Molecular mass constitution and radionuclide content in the fractions are dependent on radionuclide nature and type of soil and change along the soil profile. The major portion of 238Pu, 239 + 240Pu and 241Am (72-98%) was bound with organic matter in the soil solutions. In the case of organic horizons, these radionuclides were selectively connected with the fractions of high molecular masses (MMw > or = 2000). Radiostrontium is present principally in the fraction of inorganic compounds (19-100%) and in the low molecular mass fraction of organic matter (MMw = 350-500). A selective interaction of 137Cs with organic matter of definite molecular masses was not observed. The radionuclide was found in the "organic" fractions of a wide range of molecular masses (MMw from 350-500 to > or = 18,000) (34-97%) as well as in the fraction of inorganic compounds. The data obtained can provide the theoretical basis for explanation of higher mobility of 90Sr in soil profiles compared to other radionuclides.     

Effect of239Pu on mouse hemopoietic stem cells in different types of bone marrow cavities

Summary Repopulative activity of hemopoietic stem cells of mice given i.v. 5 kBq²³⁹Pu/mouse (166.5 kBq/kg) was followed. The activity retained was measured in the whole mouse, the skeleton and the liver. Simultaneously average cumulative skeletal dose was calculated. Quantitative parameters of the stem cell compartment and the marrow cellularity were studied in variously arranged bones (femur, pelvis, lumbar vertebra) using the exocolonizing test and cytological techniques. The effects of radiation were most marked in lumbar vertebra, less serious changes were found in pelvis and only a moderate response was present in femur. The bone marrow hemopoiesis is damaged in various bone sites to different degrees and the percentage of cells at risk appears higher in trabecular than in cortical bone.     

Distribution and biological effects of inhaled 239Pu(NO3)4 in cynomolgus monkeys.

Twenty male cynomolgus monkeys were exposed by inhalation either to an aerosol of 239Pu(NO3)4 to produce projected initial lung burdens of either 40, 10, or 4 kBq or to a carrier aerosol as a control. Animals died or were sacrificed at 0.01, 1, 3, 6, 12, 24, 40, and 99 months after inhalation, and the distribution and biological effects of the 239Pu were determined. The 239Pu cleared efficiently from the lungs so that less than 0.05 kBq remained at 99 months after exposure to 40 kBq. Total skeletal 239Pu activity was nearly constant after the first year, but the fraction of the body burden in skeleton at sacrifice increased with time up to 99 months because of clearance from other organs. Plutonium in the liver increased to a peak at 1 year and then decreased to about 10% of the peak value at 99 months. Plutonium in the testes was localized in the interstitial tissue with only 0.01 to 0.002% of the projected lung burden remaining in testes at 99 months after inhalation. Three animals exposed to 40 kBq of 239Pu died of radiation-related pulmonary pneumonitis and fibrosis. A primary papillary adenocarcinoma of the lung was identified in one animal exposed to 40 kBq initial lung burden and sacrificed 99 months after inhalation. The frequency of chromosome aberrations in blood lymphocytes was significantly elevated only in monkeys with projected deposits of 40 kBq of 239Pu. There was no change in aberration frequency in other exposure groups as a function of inhaled activity, time after exposure, or calculated total dose to the lungs. Only in monkeys that had marked radiation-induced pathological changes in the lung did the frequency of chromosome-type aberrations increase significantly, to a value about twice the control level. In cynomolgus monkeys, chromosome aberration frequency in blood lymphocytes is not a good indicator of radiation dose or damage from inhaled soluble plutonium.