Tumorigenic target cell regions in bone marrow studied by localized dosimetry of 239 Pu, 241 Am and 233 U in the mouse femur

Purpose : To study the temporal change in microdistribution of plutonium-239, americium-241 and uranium-233 in the mouse distal femur and to compare and combine calculated radiation doses with those obtained previously for the femoral shaft. Also, to relate doses to relative risks of osteosarcoma and acute myeloid leukaemia. Materials and methods : Computer-based image analysis of neutron-induced and α -track autoradiographs of sections of mouse femora was used to quantify the microdistribution of 239 Pu, 241 Am and 233 U from 1 to 448 days after intraperitoneal injection. Localized dose-rates and cumulative doses over this period were calculated for different regions of the marrow spaces in trabecular bone. The results were then combined with previous data for doses to the cortical marrow of the femoral shaft. A morphometric analysis of the distal femur was carried out. Results : Initial deposition on endosteal surfaces and dose-rates near to the trabecular surfaces at 1 day were two to four times greater than corresponding results for cortical bone. Burial was most rapid for 233 U, about twice the rate in cortical bone. As in cortical bone, subsequent uptake into the marrow was seen for 239 Pu and 241 Am but not 233 U. Cumulative doses to 448 days for different regions of trabecular marrow were greater than corresponding values for cortical marrow for each radionuclide. Combined doses reflected the greater overall volume of cortical marrow. Conclusions : Cumulative radiation doses to the 10 μ m thick band of marrow adjacent to all endosteal surfaces were in the ratio of ~7:3:1 for 239 Pu: 241 Am: 233 U. This ratio is not inconsistent with observed incidences of osteosarcoma induction by the three nuclides. Analysis of doses to different depths of marrow, however, showed that although ratios were probably not significantly different to that for a 10 μ m depth, better correlations with osteosarcomagenic risk were obtained with 20-40 μ m depths. For acute myeloid leukaemia, the closest relationship between relative risk and doses was obtained by considering only the central 5-10% of marrow, which gave a dose ratio of ~12:11:1 for 239 Pu: 241 Am: 233 U respectively.     

Tumorigenic target cell regions in bone marrow studied by localized dosimetry of 239Pu, 241Am and 233U in the mouse femur

PURPOSE: To study the temporal change in microdistribution of plutonium-239, americium-241 and uranium-233 in the mouse distal femur and to compare and combine calculated radiation doses with those obtained previously for the femoral shaft. Also, to relate doses to relative risks of osteosarcoma and acute myeloid leukaemia. MATERIALS AND METHODS: Computer-based image analysis of neutron-induced and alpha-track autoradiographs of sections of mouse femora was used to quantify the microdistribution of (239)Pu, (241)Am and (233)U from 1 to 448 days after intraperitoneal injection. Localized dose-rates and cumulative doses over this period were calculated for different regions of the marrow spaces in trabecular bone. The results were then combined with previous data for doses to the cortical marrow of the femoral shaft. A morphometric analysis of the distal femur was carried out. RESULTS: Initial deposition on endosteal surfaces and dose-rates near to the trabecular surfaces at 1 day were two to four times greater than corresponding results for cortical bone. Burial was most rapid for (233)U, about twice the rate in cortical bone. As in cortical bone, subsequent uptake into the marrow was seen for (239)Pu and (241)Am but not (233)U. Cumulative doses to 448 days for different regions of trabecular marrow were greater than corresponding values for cortical marrow for each radionuclide. Combined doses reflected the greater overall volume of cortical marrow. CONCLUSIONS: Cumulative radiation doses to the 10 microm thick band of marrow adjacent to all endosteal surfaces were in the ratio of approximately 7:3:1 for (239)Pu:(241)Am:(233)U. This ratio is not inconsistent with observed incidences of osteosarcoma induction by the three nuclides. Analysis of doses to different depths of marrow, however, showed that although ratios were probably not significantly different to that for a 10 microm depth, better correlations with osteosarcomagenic risk were obtained with 20-40 microm depths. For acute myeloid leukaemia, the closest relationship between relative risk and doses was obtained by considering only the central 5-10% of marrow, which gave a dose ratio of approximately 12:11:1 for (239)Pu:(241)Am:(233)U respectively.     

Induction of osteosarcoma and acute myeloid leukaemia in CBA/H mice by the alpha-emitting nuclides, uranium-233, plutonium-239 and amercium-241

PURPOSE: To compare tumour induction in CBA/H mice, principally osteosarcoma and acute myeloid leukaemia, resulting from exposure to the alpha-emitting nuclides, uranium-233, plutonium-239 and americium-241, and to relate differences between the three nuclides to the pattern of dose delivery within tissues. MATERIALS AND METHODS: Each nuclide was administered intraperitoneally in citrate solution to three groups of adult male CBA/H mice at levels of activity which gave estimated life-time average skeletal doses of about 0.25-0.3 Gy, 0.5-1 Gy and 1-2 Gy. Animals were carefully monitored and sacrificed as soon as they showed signs of ill health; tumours were identified by standard histopathological techniques. RESULTS: Statistical modelling by Cox regression showed that, considering all three nuclides together, there was a highly significant increase in risk of death from osteosarcoma or myeloid leukaemia with increasing dose rate. For osteosarcoma, the effect was significantly greater for 239Pu than 241Am, while separate analysis for 233U showed no significant increase with increasing dose rate. For example, the increase in relative risk of death from osteosarcoma for an increase in life-time average dose rate to bone of 1 mGyd(-1) was 4.2 (2.7-6.5) for 239Pu, 2.3 (1.4-3.4) for 241Am and 1.1 (0.4-3.1) for 233U. For myeloid leukaemia, there was no significant difference between 239Pu and 241Am in the effect of dose rate. The increase in relative risk from myeloid leukaemia for an increase in average dose rate of 1 mGyd(-1) was 1.8 (1.1-2.8) for 239Pu, 2.0 (1.4-2.9) for 241Am and 1.5 (0.8-2.7) for 233U. Significant increases in renal and hepatic carcinomas were also recorded in animals exposed to 233U and 241Am, respectively. Studies of the distribution of the nuclides within the skeleton, published separately, have shown differences in their retention in individual bones and within bone. The proportions of decays occurring near to endosteal bone surfaces and throughout bone marrow were in the order: 239Pu> 241Am>233U. CONCLUSIONS: For osteosarcoma, the relative effectiveness of the nuclides in terms of average bone dose, in the order 239Pu>241Am>233U, is consistent with the proportion of dose delivered near to endosteal surfaces. For myeloid leukaemia, the greater effectiveness of 239Pu and 241Am than 233U is consistent with their accumulation in marrow.     

Microdistribution of 239Pu in the rat skeleton. Part I. Dose dependency.

Sixty-day-old male and female rats were injected intravenously with one of three doses of monomeric 239Pu (1.11, 11.1 and 111 kBq kg-1 body weight) and were killed 1, 7, 14 or 32 days after injection. The macroscopic distribution in the skeleton as well as the microscopic distribution in the distal femur and the lumbar vertebra were studied. In general, no significant differences between the two sexes and the normalized three dose levels were found. The concentrations and dose-rates in hard tissue, marrow and near bone surfaces were lowest in the femur diaphysis and highest in the distal femur metaphysis. In each bone region the dose-rate increased in the order marrow, hard tissue, periosteal and endosteal bone surfaces. The initial dose-rates on the endosteal bone surfaces ranged from 130 mGy d-1 (femur diaphysis) up to 300 mGy d-1 (distal femur metaphysis), corresponding to an average cumulative monthly dose of 2.2 Gy (femur diaphysis) and 7 Gy (distal femur metaphysis) normalized to an injected dose of 37 kBq kg-1 body weight. After the injection of 111 kBq kg-1 body weight radiation, induced morphological changes occur to the distal femur metaphysis 32 days after injection.     

Alpha-particle-emission probabilities in the decay of 234U and photon-emission probabilities in the decays of 234U, 239Np and 243Am

Alpha-particle-emission probabilities in the decay of ²³⁴U and photon-emission probabilities in the decays of ²³⁴U, ²³⁹Np and ²⁴³Am have been measured. The α-particle-emission probabilities were measured using an ion-implanted silicon detector. The results were obtained from measurements in various solid angles and extrapolations to solid angle zero.The photon-emission probabilities were deduced from the photon-emission rates, measured with a calibrated high-purity-Ge detector, and the disintegration rates, determined by α-particle counting in well-defined solid angles.The present results improve appreciably the accuracy of the pertinent decay data.     

Testing of methyleneiminodiacetic-catechol and other aromatic chelating agents for decorporation of 238Pu and 241Am in rats

The removal of 238Pu and 241Am by five chelating agents prepared in China was compared in pilot experiments with removal by Ca-DTPA and LICAM(C). The most promising substance is quinamic acid (a methyliminodiacetic polyquinoline derivative, code name 811 or 703-73), especially in combination with Ca-DTPA. However, the best over-all reduction of both 238Pu and 241Am in all the organs studied was achieved by Ca-DTPA-administered at a ten-fold human equivalent dosage.     

Decay data evaluation project (DDEP): Updated evaluations of the 233Th and 241Am decay characteristics

The results of new decay data evaluations are presented for ²³³Th (β^?) decay to nuclear levels in ²³³Pa and ²⁴¹Am (α) decay to nuclear levels in ²³⁷Np. These evaluated data have been obtained within the Decay Data Evaluation Project using information published up to 2009.     

Determination of 241Pu in the environmental samples.

More than 70 soil samples were analysed in the last several years; results are in the range 0.10-3.74 Bq/kg dry soil, with a median of 0.49 and mean of 0.59 Bq/kg dry soil. From the analysis of more than 40 moss samples, the range of activity concentration was found to be 0.002-2.80 Bq/kg fresh mass with median 1.00 and mean value 0.30 Bq/kg fresh mass. In Hungary, the plutonium contamination comes from global fallout determined by the nuclear weapon tests, while is confirmed by plutonium isotope ratios.     

The applicability of MGA method for depleted and natural uranium isotopic analysis in the presence of actinides (232Th, 237Np, 233Pa and 241Am).

The multi-group analysis (MGA) method for the determination of uranium isotopic abundances in depleted uranium (DU) and natural uranium (NU) samples is applied in this study. A set of non-destructive gamma-ray measurements of DU and NU samples were performed using a planar Ge detector. The relative abundances of 235U and 238U isotopes were compared with the declared values of the standards. The relative abundance for 235U obtained by MGA for a "clean" DU or NU sample with a content of uranium>1wt% is determined with an accuracy of about +/-5%. However, when several actinides such as 232Th, 237Np, 233Pa and 241Am are present along with uranium isotopes simulating "dirty" DU or NU, it has been observed that MGA method gives erroneous results. The 235U abundance results for the samples were 6-25 times higher than the declared values in the presence of above-mentioned actinides, since MGA is utilized the X-ray and gamma-ray peaks in the 80-130 keV energy region, covering XKalpha and XKbeta regions. After the least-squares fitting of the spectra, it is found that the increases in the intensities of the X-ray and gamma-ray peaks of uranium are remarkably larger in the complex 80-130 keV region. On the other hand, it is observed that the interferences of the actinide peaks are relatively less dominant in the higher gamma-ray region of 130-300 keV. The results imply the need for dirty DU and NU samples that the MGA method should utilize the higher energy gamma-rays (up to 1001 keV of (234m)Pa) combined with lower energies of the spectra, which may be collected in a two detector mode (a planar Ge and a high efficient coaxial Ge).     

Activity of (239 + 240)Pu and 238Pu in atmospheric deposits.

Radioactive concentrations of (239 + 240)Pu and 238Pu were determined in rainwater samples collected at Badajoz (in a semi-arid zone in the south-west of Spain) from 1992 to 1996. Total plutonium deposition (including dry and wet deposition) was investigated during dry and wet periods. Anomalously high depositions of (239 + 240)Pu ((6.8 +/- 0.4) mBq/m2) and 238Pu ((2.2 +/- 0.2)mBq/m2) were found in the second-half of 1995. The 238Pu/(239 + 240)Pu activity ratio (0.32 +/- 0.04) obtained for that sample was higher than in global fallout.     

Spectrometry and dosimetric evaluation of the gamma-ray emissions of 241Am

New, detailed measurements have been made of the photon spectrum of the radionuclide ²⁴¹Am. Observations, recorded for a 95% confidence level over local background, provide affirmation of a number of lines previously considered to be of equivocal existence. A number of hitherto unreported emissions are similarly observed. Peak areas, expressed as a percentage of that for the 59.54 keV emission, have been ascribed to all lines of the detailed spectrum. This leads to an estimated increase in the value of exposure calculated from the measured fluence spectrum, relative to that from the 59.54 keV line, of (3.1 ± 0.8)%, taking into account all emissions beyond the predominating 59.54 keV gamma-ray emission.     

Distribution of 241Am in offspring from BALB/c mice injected with 241Am at 14 days of gestation: relation to calcium and iron metabolism and comparison with distribution of 241Am after injection of adults

Pregnant mice were given intravenous injections of 241Am citrate at 14 days of gestation. The fetal skeleton had a higher or similar uptake of 241Am per gram of fresh tissue than the liver. In comparison, the liver in adults concentrated 5 to 20 times more 241Am per gram of fresh tissue than the bones. Measurement of changes in calcium and iron content and concentration with time, showed that in the developing mice intensive calcification of bones determined the uptake of 241Am. The 241Am uptake was related to the calcium concentration of the fetal bones, which was greater at 14 days of gestation in the anterior bones, the mandibles and calvaria, than in the ribs and femurs. Transfer of 241Am to pups via milk resulted in further accumulation of 241Am in the skeleton and liver. The incorporation in the skeleton persisted after weaning and contributed to the lifetime body burden. The 241Am concentration decreased rapidly with time after injection in relation to the growth of the organs. Radiation dose rates and cumulative radiation doses were calculated for liver and bones of contaminated offspring.     

Competence of alpha spectrometry analysis algorithms used to resolve the 241Am and 243Am alpha peak overlap.

Five alpha spectrometry analysis algorithms were evaluated for their ability to resolve the 241Am and 243Am peak overlap present under typical low-level counting conditions. The major factors affecting the performance of the algorithms were identified using design-of-experiment combined with statistical analysis of the results. The study showed that the accuracy of the 241Am/243Am ratios calculated by the algorithms depends greatly on the degree of peak deformation and tailing. Despite the improved data quality obtained using an algorithm that may include peak addition and tail estimation, the accurate determination of 241Am by alpha spectrometry relies primarily on reduction of peak overlap rather than on algorithm selection.     

Accelerator mass spectrometry measurement of 240Pu/239Pu isotope ratios in Novaya Zemlya and Kara Sea sediments.

Generally low levels of plutonium in environmental samples, often combined with limited sample sizes, necessitate reliable low-level techniques for determination of Pu isotopes. Accelerator mass spectrometry (AMS) has proved to be a powerful method for measuring low-level Pu activity concentrations and Pu isotope ratios. Based on procedural blanks, detection limits for AMS were below 1 fg Pu (equivalent to ca. 2 microBq 139Pu), which can compete with both TIMS, high sensitivity ICP-MS, and certainly alpha-spectrometry, while showing less interference, memory and matrix effects as compared to routine ICP-MS techniques. In addition to low detection limits, the technique offers the advantage of giving information on Pu isotope ratios. Measurements of sediments collected from dumping sites at Novaya Zemlya showed deviation from global fallout 240Pu/239Pu ratios.     

Simulation of radionuclides 99Tc and 243Am migration in compacted bentonite.

The distribution coefficients of radionuclides derived from batch experiments are used to evaluate the migration behavior of radionuclides (99)Tc and (243)Am in compacted bentonite after different times. The effects of times, dispersion coefficient, distribution coefficient and pore water velocity on the concentration distribution of (99)Tc and (243)Am in the environment are also calculated from the theoretical migration equation. (99)Tc is poorly sorbed to bentonite and moves quickly into the environment. Migration of radionuclide increases with increasing dispersion coefficient and decreasing distribution coefficient. The effects of water velocity on the migration of Tc and Am are obvious. Most (243)Am is retained in the first several meters, and 20 m of the backfill-compacted bentonites are sufficient to prevent the migration of radionuclide Am from the repository to the environment.