Microdistribution and localized dosimetry of the alpha-emitting radionuclides 239Pu, 241Am and 233U in mouse femoral shaft

PURPOSE: To analyse the temporal change in microdistribution of 239Pu, 241Am and 233U in mouse femur and to compare the calculated radiation doses with regions of the bone marrow thought to contain target cells for osteosarcoma and leukaemia with relative risk for those diseases. MATERIALS AND METHODS: Neutron-induced and alpha-track autoradiographs were prepared from femora of the CBA/H mouse that had been injected with 40 kBq kg(-1) radionuclide between 1 and 448 days previously. Computer-based image analysis of the autoradiographs was performed and dosimetric methods applied to obtain radiation dose-rates to different regions of the marrow cavity. RESULTS: Initially each radionuclide deposited on endosteal and periosteal bone surfaces; 241Am was additionally deposited on vascular canal surfaces. Redistribution resulted in 233U being incorporated into bone, while 239Pu and 241Am showed transfer into both bone volume and marrow. Accumulation in the central marrow peaked at 112-224 days post-injection, but subsequently was cleared by 448 days. Cumulative doses to both osteosarcomagenic and myeloid leukaemogenic target cell regions showed the trend 239Pu > 241Am > 233U. CONCLUSIONS: Calculation of cumulative doses to a 10-microm layer of marrow adjacent to bone surfaces appears to be a suitable predictor for risk of osteosarcoma. Risks of myeloid leukaemia in the mouse are better predicted by considering the central marrow as the target region rather than average dose to all marrow.     

The Induction by 239Pu of Myeloid Leukaemia and Osteosarcoma in Female CBA Mice

Summary

Plutonium-239 was injected into 12-week-old female CBA/H mice in the range 1·85–18·5 kBq kg^?1 either as a single injection or as 16 injections spaced at 3·5 day intervals over eight weeks. There was a highly significant increase in the yield of fully developed osteosarcomas with increased amounts of ²³⁹Pu for both modes of injection. Osteosarcomas too small to be diagnosed radiographically were also seen in many bones and small but significant yields of myeloid leukaemia were seen in animals given plutonium. Although more myeloid leukaemia was seen in the mice given plutonium in divided amounts than in those given the plutonium in a single injection it could not be shown that multiple injection significantly affected the yield of either late effect.     

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.     

In utero haemopoietic sensitivity to alpha,beta or X-irradiation in CBA/H mice

Purpose : To assess in utero sensitivity to x-rays, α -emissions from plutonium-239 and β -emissions from tritium in terms of induction of chromosomal aberrations in bone marrow cells. Materials and methods : CBA/H mice were exposed to a single dose of X-rays (0.5Gy) on either day 7 or day 14 of pregnancy or given 239 Pu (100 kBq kg -1) by intraperitoneal injection on either day 6 or day 13. Tritium was administered to mice throughout pregnancy as either tritiated water, ad libitum in drinking water (total intake averaged 130 MBq), or as homogenized tritiated cress, administered by gastric intubation (total 60 MBq). Irradiated and unexposed control mice and their offspring were sacrificed at 2-8 weeks after birth. Direct metaphase preparations from femoral bone marrow cells from mothers and offspring were used for G-band analysis. Results : The incidence of stable aberrations was significantly and similarly increased in neonatal and maternal marrow samples after exposure to X-rays, 239 Pu or 3 H. The estimated average bone absorbed doses from 239 Pu in pregnant females were similar to the X-ray dose of 0.5 Gy, suggesting a low RBE for α -irradiation in adults. The similar levels of damage observed in neonates after X-irradiation and 239Pu exposure are indicative of greater in utero sensitivity to α -irradiation since the overall estimated in utero α -particle doses to haemopoietic tissue were much lower. In utero doses from 3 H and corresponding maternal doses were around 0.5Gy, showing no evidence of greater in utero sensitivity, no significant difference between the effects of the two forms of tritium, and were consistent with an RBE value of 1-2. Conclusions : Comparison of stable aberration yields in haemopoietic cells suggests a greater sensitivity to α -particles from 239 Pu than X-rays or β -particles from 3 H for irradiation in utero but a low RBE value in adults.     

Late effects of X-irradiation on haemopoietic stem cells in CBA/H mice

CBA/H male mice have been used to study the recovery of haemopoietic stem cells following 3 Gy whole-body X-irradiation. Despite significant proliferation haemopoietic stem cells (measured as spleen colony-forming units or CFU-S) did not recover to control values and their numbers remained sub-optimal at 600 days post-irradiation. At this time there were significant increases in both proliferation and self-renewal characteristics of the CFU-S but no impairment of the capacity of bone marrow cells to rescue and repopulate lethally irradiated transplant recipients.     

In utero haemopoietic sensitivity to alpha, beta or X-irradiation in CBA/H mice.

PURPOSE: To assess in utero sensitivity to x-rays, alpha-emissions from plutonium-239 and beta-emissions from tritium in terms of induction of chromosomal aberrations in bone marrow cells. MATERIALS AND METHODS: CBA/H mice were exposed to a single dose of X-rays (0.5Gy) on either day 7 or day 14 of pregnancy or given (239)Pu (100 kBq kg(-1)) by intraperitoneal injection on either day 6 or day 13. Tritium was administered to mice throughout pregnancy as either tritiated water, ad libitum in drinking water (total intake averaged 130 MBq), or as homogenized tritiated cress, administered by gastric intubation (total 60 MBq). Irradiated and unexposed control mice and their offspring were sacrificed at 2-8 weeks after birth. Direct metaphase preparations from femoral bone marrow cells from mothers and offspring were used for G-band analysis. RESULTS: The incidence of stable aberrations was significantly and similarly increased in neonatal and maternal marrow samples after exposure to X-rays, (239)Pu or (3)H. The estimated average bone absorbed doses from (239)Pu in pregnant females were similar to the X-ray dose of 0.5 Gy, suggesting a low RBE for alpha-irradiation in adults. The similar levels of damage observed in neonates after X-irradiation and 239Pu exposure are indicative of greater in utero sensitivity to alpha-irradiation since the overall estimated in utero alpha-particle doses to haemopoietic tissue were much lower. In utero doses from (3)H and corresponding maternal doses were around 0.5Gy, showing no evidence of greater in utero sensitivity, no significant difference between the effects of the two forms of tritium, and were consistent with an RBE value of 1-2. CONCLUSIONS: Comparison of stable aberration yields in haemopoietic cells suggests a greater sensitivity to alpha-particles from (239)Pu than X-rays or beta-particles from (3)H for irradiation in utero but a low RBE value in adults.     

Alpha-particle irradiation of haemopoietic tissue in pre- and postnatal mice. 1: Distribution of plutonium-239 after mid-term contamination.

Pregnant mice (at 13 days gestation) and age-matched controls were injected with 30 kBq 239Pu/kg and the distribution of plutonium in maternal and foetal tissues measured. Approximately 2% of the activity injected into the mother reached each foetus in 24 h, 95% of which was contained in membranes and placenta. The concentration of plutonium in foetal liver was 3 times the average foetal body concentration; both liver and body concentrations in the foetus increased by the end of gestation. Each pup accumulated only 0.01% extra injected activity after 9 days lactation and, as the resulting concentrations in the neonatal skeleton were low, we conclude that the greatest haemopoietic risk to the offspring from mid-term contamination in utero is in the foetal liver (which received an average dose of 10-14 mGy between the time of mid-term contamination and birth). By the end of gestation about one-quarter of the original activity was transferred to foetal tissues from the maternal liver and skeleton. No significant changes in maternal distribution were detected as a result of lactation. The results of this study are discussed, along with a compilation of previously published data.     

Absence of the effects of 50 Hz magnetic fields on the progression of acute myeloid leukaemia in rats

PURPOSE: As the most recent epidemiological studies provide no definite conclusions about the effects of 50/60 Hz magnetic fields (MFs) on the incidence of leukaemia in humans, animal models in a well-controlled environment are useful for evaluating the possibility of an association between MFs and leukaemia. The present study was designed to determine whether 50 Hz magnetic fields can alter the progression of leukaemia. MATERIALS AND METHODS: A well-characterized model of transplantable acute myeloid leukaemia in rats was used for the first time. This model is closely related to human acute myeloid leukaemia, the type most frequently reported in epidemiological studies of adults. After leukaemic cell implantation, rats were exposed to a sinusoidal 50 Hz MF of 100 microT for 18 h a day, 7 days a week, throughout leukaemia progression. The parameters investigated were: survival time, body weight, haematologic parameters, infiltration of blood, bone marrow, spleen and liver by leukaemic cells. RESULTS: The results showed no significant changes (p > 0.05) in leukaemic MF-exposed versus unexposed rats for any of the parameters involved in leukaemia progression. CONCLUSION: These data do not support the hypothesis that 50 Hz magnetic fields influence leukaemia progression in humans.     

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).     

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.     

蛋白聚糖Versican V1区诱导小鼠脊柱炎和骶髂关节炎模型的建立

目的 建立自身免疫性强直性脊柱炎(AS)实验动物模型,并探讨重组人蛋白聚糖Versican的G1区多肽(VG1)在其脊柱和骶髂关节炎发病中的作用。方法 用自然折叠的VG1和完全弗氏佐剂免疫BALB／c小鼠,诱导产生脊柱炎和骶髂关节炎,建立自身免疫性AS实验动物模型。采用组织病理学方法显示脊柱炎小鼠的发病程度和病理学特征。结果 用VG1和完全弗氏佐剂免疫的实验组小鼠脊柱炎和骶髂关节炎的发病率分别为35．0％和12．5％,未出现外周炎的临床症状。组织病理学结果显示,脊柱韧带与椎间盘连接处、椎间盘和骶髂关节有大量的单个核细胞浸润。结论 成功建立了VGl诱导的小鼠脊柱炎模型,并发现针对蛋白聚糖Versican的免疫反应参与了BALB／c小鼠脊柱炎和骶髂关节炎的发病,为进一步深入研究人类AS的发病机制及其临床治疗提供了有价值的实验材料。     

The efficacies of pure LICAM(C) and DTPA on the retention of plutonium-238 and americium-241 in rats after their inhalation as nitrate and intravenous injection as citrate

The pure carboxylated catechoyl amide LICAM(C) and the calcium and zinc salts of diethylenetriaminepenta-acetic acid (DTPA), were tested for efficacy for removing 238Pu and 241Am from rats after inhalation of the nitrate or intravenous injection of the citrate. The results were compared with the efficacy of methylated LICAM(C) used in previous experiments. It was shown that: (1) after inhalation of 238Pu nitrate, DTPA was far superior to pure LICAM(C); (2) after intravenous injection of 238Pu citrate, the infusion of DTPA plus LICAM(C) was only marginally more effective than DTPA alone; and (3) after inhalation or intravenous injection of 238Pu plus 241Am, the efficacy of pure LICAM(C) was only marginally more effective than the methylated form and neither form was effective for the decorporation of 241Am. It was concluded that DTPA, at present, remains the chelating agent of choice for treating persons accidentally contaminated with transportable forms of Pu and Am.     

Standardization and photon emission probabilities in the decay of 237Np/233Pa

The activity concentration of a ²³⁷Np solution was determined by 4πα counting, by alpha particle spectroscopy with defined solid angle and by liquid scintillation counting (LSC). These methods yielded results which differ by less than 0.1% from the mean, the relative standard uncertainties being 0.23% (4πα), 0.27% (LSC) and 0.5% (solid angle). X-ray and gamma-ray emission probabilities of several transitions were measured using semiconductor detectors.     

Chromosomal instability in haemopoietic cells of the foetus, mother and offspring after in utero irradiation of the CBA/Ca mouse.

PURPOSE: The present study was conducted to test the susceptibility of the mouse foetus to transmit chromosomal instability to the haemopoietic stem cells of offspring after in utero X-or plutonium-239-irradiation. MATERIALS AND METHODS: Pregnant CBA/Ca-mice were injected with 80 kBq/kg 239Pu or X-irradiated with 1 Gy X-rays on days 13 or 14 of gestation. CFU-A cultures were grown from haemopoietic stem cells sampled from foetal liver and the bone marrow from the offspring and from the mother. Non-clonal, unstable chromosomal aberrations were scored in metaphases from individual stem cell colonies. RESULTS: The relative excess (RE) of unstable chromosomal aberrations in foetal liver cells irradiated with 1 Gy X-rays increased from 1.6 at day 2 up to 2.7 at day 4 after irradiation. In the bone marrow cells from the mother, this value was 1.8 (average from cells sampled at days 3 and 14 after irradiation). After injection of the pregnant mice with 235Pu, the yield of unstable chromosomal aberrations per cell was 0.14+/-0.03 (RE approximately 10) in descendants of bone marrow cells from the mother, 0.11+/-0.02 (RE = 10) in descendants of foetal liver cells and 0.16+/-0.05 (RE = 10) in descendants of bone marrow cells from the offspring. CONCLUSIONS: From the numerical analysis of non-clonal, unstable aberrations in haemopoietic cells from the foetus, the mother and the offspring after in utero irradiation, it was concluded that in utero irradiation of the CBA/Ca mouse was not more efficient in inducing chromosomal instability in the offspring than in the foetus or the mother. All three cell populations exhibited a similar degree of unstable aberrations, both in terms of the absolute numbers of non-clonal aberrations and in terms of relative excess compared with unexposed controls.