Injection Of Plutonium Research Articles

A Method for Continuous (239)Pu Determinations in Arctic and Antarctic Ice Cores.

Atmospheric nuclear weapons testing (NWT) resulted in the injection of plutonium (Pu) into the atmosphere and subsequent global deposition. We present a new method for continuous semiquantitative measurement of (239)Pu in ice cores, which was used to develop annual records of fallout from NWT in ten ice cores from Greenland and Antarctica. The (239)Pu was measured directly using an inductively coupled plasma-sector field mass spectrometer, thereby reducing analysis time and increasing depth-resolution with respect to previous methods. To validate this method, we compared our one year averaged results to published (239)Pu records and other records of NWT. The (239)Pu profiles from the Arctic ice cores reflected global trends in NWT and were in agreement with discrete Pu profiles from lower latitude ice cores. The (239)Pu measurements in the Antarctic ice cores tracked low latitude NWT, consistent with previously published discrete records from Antarctica. Advantages of the continuous (239)Pu measurement method are (1) reduced sample preparation and analysis time; (2) no requirement for additional ice samples for NWT fallout determinations; (3) measurements are exactly coregistered with all other chemical, elemental, isotopic, and gas measurements from the continuous analytical system; and (4) the long half-life means the (239)Pu record is stable through time.

Anomalously high excretion of Pu in urine following inhalation of plutomium nitrate?

A study of the biokinetics of inhaled plutonium nitrate in two volunteers has been carried out. Low doses (approximately 80 microSv) were achievable because tracers of high isotopic purity were used: 237Pu (measurable by X ray spectrometry) and 244Pu (measurable by accelerator mass spectrometry). Lung retention, amount in blood, uptake to the liver and skeleton, and urinary and faecal excretion were measured. The measured urinary excretion rates are about a factor of three higher than those predicted from urine excretion data measured following intravenous injection of plutonium to the same volunteers. If similar biokinetic behaviour occurs in workers exposed to plutonium nitrate, intakes by inhalation and corresponding committed doses assessed by urine bioassay could be consistently overestimated by a similar factor.

Efficacies of Three Chelating Agents on Removal of Plutonium in Rats: Comparison of CBMIDA, 3,4,3-LIHOPO and Ca-DTPA

The effects of three chelating agents, CBMIDA, 3, 4, 3-LIHOPO, and Ca-DTPA, for removing Pu-239 in rats were compared. Forty female Wistar rats, 2 months old, were pre-injected intraperitoneally with 37, 000Bq/kg of plutonium nitrate and divided into four groups. Thereafter the rats of three groups were injected intraperitoneally with three chelating agents at a dose of 30μmol/kg, equivalent to a daily recommended human dose of Ca-DTPA, at intervals of 24hr for 3 days, beginning 30min after plutonium injection on the first day of treatment. Urine and feces were collected every 24hr. On day 4, the rats were sacrificed to obtain organs including the liver, kidney, and spleen, as well as the femur and serum. The amounts of excreted plutonium in urine of the CBMIDA and Ca-DTPA groups were increased significantly over that in the 3, 4, 3-LIHOPO and control groups, while those in the feces of the 3, 4, 3-LIHOPO group were increased significantly over the other groups on the first day. The total amount of excreted plutonium by 3 day-treatments was highest in the 3, 4, 3-LIHOPO group. The toxicity of each agent was discussed. It is concluded that at the same doses, the effect of 3, 4, 3-LIHOPO was superior to CBMIDA and Ca-DTPA for removing plutonium in rats.

Effects of Four CBMIDA Analogues on Removal of Plutonium in Rats.

We have previously reported that the injection of a newly developed chelating agent, catechol-3, 6-bis (methyleneiminodiacetic acid) (CBMIDA), removes plutonium particularly from the bones, more effectively than DTPA in rats. Nevertheless, the removed plutonium is later redistributed to the kidneys, an undesirable phenomenon, in chelation therapy. Therefore, it was considered of interest to survey the effects of four new analogues of CBMIDA (C-I-C-IV) on the removal of plutonium in rats and compared with the CBMIDA. After the intravenous injection of plutonium, CBMIDA and its analogues were administered daily, for 2 weeks by intraperitoneal injection or by oral administration. The gathered data indicated that the intraperitoneal administration of two analogues, C-II and C-III significantly decreased the amount of plutonium in the bones and liver (p<0.01), and that in the spleen, testis and kidney were also reduced. In conclusion, the results indicate that among the tested agents, these two chelating agents present useful characteristics for the chelation therapy in individuals contaminated with plutonium.

High frequency of leukemic lymphomas with osteosarcomas but no myeloid leukemias in C3H mice after 239Pu citrate injection.

Female C3H strain mice, which do not spontaneously exhibit frequent bone tumors and myeloid leukemias, were injected intraperitoneally with various doses of 10 to 12,000 Bq/animal of monomeric 239Pu citrate to clarify lifetime carcinogenesis caused by alpha-particles distributed mainly in the skeleton. Survival time was reduced significantly at mean skeletal doses of more than 2.93 Gy and was accompanied by marked life-shortening as compared to the controls due to an earlier increase in neoplastic or non-neoplastic death. Bone tumors, almost all of which were osteosarcomas, were not found in the controls, whereas their incidence increased sharply to a maximum of 96% at 6.92 Gy, then dropped at higher doses (20% at 42.4 Gy). Although lymphoid tumors were present in 20% of the control animals, their incidence dropped to zero at 6.92 Gy, then increased at higher doses (36% at 25.5 Gy). Non-thymic, mostly pre-B cell type, leukemic lymphomas mainly occurred at early time after 239Pu-injection; whereas, in the controls thymic, lymphocytic or histiocytic lymphomas occurred only at a later time. Of the other soft tissue tumors, neither myeloid leukemias nor myelogenous neoplasms were found in the controls or the 239Pu-injected animals. Tumors affecting the lungs, liver, ovaries, and skin were much fewer or not found at mean doses of more than 2.93 Gy. These results indicate dose-dependent, differential tumor induction resulting from bone and lymphoid tumor competition after an injection of plutonium.

Effects of CBMIDA and Zn-DTPA in Drinking Water on Removal of Plutonium in Rats.

The effects of the oral administration of CBMIDA [catechol-3, 6-bis (methyleiminodiacetic acid)], given in drinking water, on the removal of plutonium in rats were compared to those of Zn-DTPA. Male Wistar rats received a daily dose of 120μmol/kg or 1, 200μmol/kg of CBMIDA or Zn-DTPA, given in drinking water, for 4 weeks after plutonium injection. The content of plutonium in bone, liver, kidney, spleen, and testis was measured by a liquid scintillation spectrometry after treatment of the organs by a wet ash method. The plutonium content of each organ in the 120μmol/kg groups of CBMIDA and Zn-DTPA was not significantly reduced. The content of plutonium in the 1, 200μmol/kg groups of both CBMIDA and Zn-DTPA was, however, significantly reduced, to 65.7% (p<0.001) and 76.8% (p<0.05), respectively of the control in bone, and to 66.6% (p<0.05) and 44.0% (p<0.01), respectively, in liver. There were no significant decreases in kidney, spleen, and testis in the 1, 200μmol/kg dose CBMIDA group, but there were significant decreases in these organs in the 1, 200μcmol/kg dose Zn-DTPA group. These results showed that, when given orally, CBMIDA was more effective in removing plutonium from bone than Zn-DTPA, a finding similar to the results were achieved with the intravenous injection of both agents in our previous study.

Differential induction of bone and hematopoietic tumors in C3H mice after the injection of 239Pu citrate.

Although alpha-emitting plutonium is easily distributed in the skeleton via circulation and subsequently induces bone tumors, there is little evidence that hematopoietic neoplasias are highly induced even though bone marrow stem cells are irradiated internally by alpha particles. We injected groups of female C3H strain mice with doses of 239Pu citrate from 500 to 10000 Bq to investigate the dose-related spectrum of tumor types induced during a lifetime. Survival time was reduced strikingly in all the injected mice due to much earlier induction of bone and lymphoid tumors as compared to the control animals that showed a variety of soft tissue tumors after a longer period of survival. Induction of osterosarcomas was dose-dependent, being maximal in 70% of the animals that received a mean skeletal dose of 10 Gy or less, but was 48% or less at 20 Gy or more. Non-thymic lymphomas accompanied by lymphocytic leukemia were observed in only 4-6% of the animals that received a dose of 10 Gy or less whereas it was maximal in 17-19% at 20 Gy or more. In contrast, there were no bone tumors in the control animals, rather thymic lymphomas or histiocytic lymphomas were found very late in 20% and other soft tissue tumors, including lung, liver and ovary tumors, were noted in 60%. Neither myeloid leukemia nor other myelogenous neoplasias were found in the control and 239Pu-injected animals that received a mean skeletal dose of 3 Gy or more. These results indicate that the differential induction of bone tumors and hematopoietic tumors in mice depends on the dose range and the time after the injection of plutonium.

Removal of Plutonium by a New Type Calcium and Combination of the Calcium and Ca-DTPA in Rats.

Effects of a new type of calcium product (Seaweed-calcium complex: SWCa) and combination of SWCa and Ca-DTPA on removal of injected 239Pu were examined in rats. SWCa is a natural product consisting of mixed calcined oyster shell (COS) which is composed of calcium salt probably in the form of calcium oxide and a natural material extracted from seaweed to transport calcium actively throughout the small intestine. In experiment I, a 2% solution of SWCa, COS, CaO, CaCl2 or CaCO3 was injected into the small intestinal loops of rats to compare the intestinal absorption rate of each calcium salt. In experiment II, 25 male Wistar rats, 3 months of age, were divided into five groups given; a control diet with 1% CaCO3 (group A), a SWCa diet with 1% SWCa to replace the 1% CaCO3 after plutonium injection (group B), a SWCa diet 1 week before plutonium injection until the end of the experiment (group C), a SWCa diet and intraperitoneal injections of a daily dose of 150μmol/kg of Ca-DTPA (group D), and a control diet and intraperitoneal injections of the same dose of Ca-DTPA as group D (group E). The rats were injected intravenously with plutonium, 1.85×104Bq/kg, and killed 14 days later and the femur and liver were excised. All excreta were collected at 24-h intervals during the experimental period. The plutonium concentration was measured by a liquid scintillation spectrometry after a wet ashing treatment.The levels of serum total and ionic calcium were elevated more rapidly and were higher after the injection of SWCa than after those of COS, CaO and CaCO3. The percent of plutonium content to administered dose in the skeleton was 69.3, 63.6, 58.8, 10.4 and 19.0%, and that in the liver was 7.74, 6.93, 6.43, 0.22 and 0.35% for groups A, B, C, D and E, respectively. The plutonium contents in the urine and feces were increased during the first 2-3 days after plutonium injection in the SWCa groups. The results indicated that the elevation of serum calcium by the oral administration of SWCa could lower the plutonium content in the skeleton and liver both before and after plutonium injection and the effects were increased by the combination of SWCa and Ca-DTPA. In conclusion, SWCa not only lowered the plutonium content after exposure but also prevented plutonium deposition in the bones and liver.

Effects of CBMIDA(Catechol-3,6-bis(methyleiminodiacetic acid)) on Removal of Plutonium in Rats.

Effects of CBMIDA [catechol-3, 6-bis(methyleiminodiacetic acid)] on injected 239Pu were examined in rats; in our previous studies, CBMIDA had almost the same toxicity as those of DTPA and EDTA. Rats were injected intravenously with 239Pu (1.85×104Bq/kg) and divided into four groups of five rats each. Three groups were each injected intraperitoneally with a daily dose of 150μmol/kg of CBMIDA, Ca-DTPA or Zn-DTPA for 2 weeks, beginning at about 1h after plutonium injection. Rats were sacrificed 14 days later and the femur and liver were removed. All excreta were collected at 24-h intervals during the experimental period. Plutonium contents of the femur, liver, feces and urine treated by a wet ashing method were measured by a liquid scintilation spectrometry.The plutonium contents in the skeleton of administered dose were 11.5% for CBMIDA group, 19.0% for Ca-DTPA group, and 26.9% for Zn-DTPA group, whereas that was 63.9% for the control; those in the liver were 0.62% for CBMIDA group, 0.35% for Ca-DTPA group and 0.54% for Zn-DTPA group, whereas that was 7.74% for the control. The data obtained indicate that CBMIDA is superior to Ca-DTPA and Zn-DTPA on removing plutonium from bone, and also has almost the same effectiveness on removing it from liver as those of both Ca-DTPA and Zn-DTPA. The higher effectiveness of CBMIDA on removal of plutonium from the skeleton might be, besides the stronger chelating action, due to the inhibition of plutonium deposition into bone, judging from the results of our previous study wherein the effects of CBMIDA on bone metabolism were examined in beagle dogs.In conclusion, taking together the results obtained in this study and those from our previous studies on the toxicity, it was demonstrated that CBMIDA could be utilized, as a new chelating agent, to remove plutonium from human body.

Effect of plutonium-239 on the mitotic activity of mouse bone marrow cells.

Mitotic index of the bone marrow cells was studied in femoral bone marrow of mice given 313 kBq 239Pu kg-1. The attention was turned to the femoral midshaft and the mitosis concentration, intensified by Colcemid stathmokinetic effect, was evaluated in a sampling field from endosteal surface to the central venous canal, throughout 68 weeks. It has been found that the plutonium effect in the sampling band is rather uniform except the points in subendosteal zone early after plutonium injection, where the mitotic index was reduced in such a way that the mitotic gradient, observed in controls, was affected. The mitotic activity in femoral diaphysis of plutonium injected mice was mobilized approximately till the 30th week of contamination. Later it deteriorated progressively. The results are discussed and should not be regarded as representative for the entire bone marrow hemopoiesis.

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.

Reducing the Cancer Risk of 239 Pu by Chelation Therapy

Groups of adult female C57BL/Do mice were injected intraperitoneally with graded activities of monomeric 239Pu(IV) citrate at 10 weeks of age. Beginning 3 days after plutonium injection, some mice received repeated subcutaneous injections of Zn Na3 diethylenetriaminepentaacetate (Zn-DTPA). Each injection was 37 mumol Zn-DTPA/kg body weight. To evaluate protection from bone sarcoma, brief, intermediate, or protracted chelation therapies were administered to groups of mice. The brief chelation therapy covered a 2-week period, the intermediate therapy 2 months, and the protracted therapy 1 year. The mice were followed throughout life and examined for bone sarcoma. Both skeletal dose and bone sarcoma risk were reduced by chelation. The bone sarcoma incidences in the mice given chelation treatments generally fell below the dose-response curve for the mice not given DTPA, indicating that the cancer risk was reduced more than that corresponding to the decreased skeletal dose. This results suggests that Zn-DTPA preferentially removed Pu from the most carcinogenic locations in the skeleton, such as on bone surfaces near living cells.

Failure of Interferon to Inhibit Plutonium-Induced Osteosarcomas in Mice2

The injection of murine interferon three times weekly in dose levels of 1,250, 5,000, or 20,000 U produced no significant antitumor effect against primary 239Pu-induced osteosarcomas in C57BL/6J mice. The interferon treatment was begun 94 days after the plutonium injection, which is well before the radiographic or microscopic appearance of neoplasia, and was continued until the moribund state or death. The average radiation dose accumulated by the skeleton at the time of first treatment was approximately 300 rad. The largest dose of interferon studied, 20,000 U/injection, was approximately 3 X 10(6) U/m2 of body surface, or 10(6) U/kg body weight.

Dose-response Relationships for Bone Cancers from Plutonium in Dogs and People

The risk of bone cancers developing from internally deposited plutonium must be estimated from studies in laboratory animals because no plutonium-induced cancers have been observed in people. Studies of the effects of 226Ra and 239Pu injected into beagle dogs at the University of Utah and 238PuO2 inhaled by beagle dogs at the Inhalation Toxicology Research Institute provide a key link to understanding the longterm effects of inhaled alpha-emitting radionuclides in people. Injected radium and plutonium are rapidly deposited in bone whereas plutonium deposited in lung by inhalation is translocated to bone more slowly, depending on its chemical form. The development of bone cancers is a late occurring effect seen after either injection of plutonium or radium or inhalation of plutonium. The incidence of bone cancers from alpha radiation to the skeletons of dogs was compared to bone cancer incidences in radium dial painters to estimate bone cancer risk from inhaled plutonium in people. A risk factor of 1200 bone cancers/106 rad to skeleton (average dose) was estimated.

Dose-response Relationships for Bone Cancers from Plutonium in Dogs and People

The risk of bone cancers developing from internally deposited plutonium must be estimated from studies in laboratory animals because no plutonium-induced cancers have been observed in people. Studies of the effects of 226Ra and 239Pu injected into beagle dogs at the University of Utah and 238PuO2 inhaled by beagle dogs at the Inhalation Toxicology Research Institute provide a key link to understanding the longterm effects of inhaled alpha-emitting radionuclides in people. Injected radium and plutonium are rapidly deposited in bone whereas plutonium deposited in lung by inhalation is translocated to bone more slowly, depending on its chemical form. The development of bone cancers is a late occurring effect seen after either injection of plutonium or radium or inhalation of plutonium. The incidence of bone cancers from alpha radiation to the skeletons of dogs was compared to bone cancer incidences in radium dial painters to estimate bone cancer risk from inhaled plutonium in people. A risk factor of 1200 bone cancers/106 rad to skeleton (average dose) was estimated.

Effect of polymeric plutonium on the hematopoietic activity in the bone marrow of mice.

The hematopoietic activity in the bone marrow was investigated in male CF#1 mice at 28 and 56 days after intravenous injection of polymeric plutonium-239 at the dose level of 15 μCi/kg, 10 μCi/kg and 5 μCi/kg of body weight. The number of nucleated cells in the femoral marrow decreased in proportion to the amount of plutonium injected. The number of in vivo colony forming units per femoral marrow also decreased with the increase of the dose of plutonium. No significant change was observed in the blood clearance of 69Fe with the exception of the group at 56 days after injection of the heighest dose. In this group 59Fe in the blood disappeared very rapidly within 2 minutes after injection of 59Fe. With the injection of plutonium, 59Fe incorporation into circulating erythrocytes was depressed even in the lowest dose group. Except for the group at 56 days after injection of the highest dose, 59Fe in the femur increased. The possibility of ineffective erythropoiesis by polymeric plutonium was discussed. From the facts investigated in this study, we may conclude that the hematological activity in the bone marrow was disturbed by as low as 5 μCi/kg of polymeric plutonium, the dose with which clinically detectable anemia had not been induced.

Decorporation of Monomeric Plutonium from the Dog by Glucan and/or DTPA

Monomeric 239-plutonium was injected intravenously into beagle dogs to determine the effectiveness of DTPA (diethylenetriaminepentaacetic acid) and glucan, a polysaccharide derived from yeast cell walls, as agents for plutonium decorporation. DTPA therapy (100 mg/kg) was initiated six days after plutonium injection and continued, on a twice weekly basis, for 84 days. Glucan (15 mg/kg), given in conjunction with DTPA to a second group of dogs, was administered on days 6, 34, and 62. Control animals received sterile saline in place of both DTPA and glucan. When all animals were sacrificed on day 90, the liver burden in control dogs was the same as previously determined at day 6. DTPA therapy removed over 96% of this plutonium; removal from spleen, lungs, kidneys, testes, muscle, and lymph nodes ranged between 50 and 90%. The total skeletal content was also reduced by 50%. Adjunct therapy with glucan did not result in significant additional removal of plutonium, probably because of the high effectiveness of DTPA given alone. Species differences in the deposition of plutonium in liver as related to the effectiveness of DTPA therapy, with possible implications for man, are discussed.

Induction of mesotheliomas and sarcomas from "hot spots" of 239 PuO 2 activity.

AbstractAlbino rats were given an intraperitoneal injection of approximately 2.8 μCi, submicron-sized 239PuO2 particles. From 30 to 35% of the initially injected dose was found in the omentum within fibrous adhesions by 6 months after plutonium injection. About 27% of the animals developed mesotheli

Biliary plutonium excretion in the rat.

About 50% of the plutonium excreted into the perfused intestine of the rat during the first hour after plutonium injection arrived by way of the bile. After DTPA treatment, the proportion excreted in bile was increased to 75% and the bile plutonium concentration increased 15–20 fold. The prompt appearance of plutonium in the bile after injection suggests that the transfer from blood to bile of at least a portion of the plutonium occurs by a relatively direct process.

The radiation dose-rates near bone surfaces in rabbits after intravenous or intramuscular injection of plutonium 239.

In a previous paper (Bleaney, 1968) a description was given of the pattern of deposition of plutonium on the bone surfaces of six-week-old rabbits following an intravenous injection of plutonium nitrate. The dose-rates near bone surfaces were estimated from α track counts obtained by autoradiography. The experiments have been repeated with seven-month-old, fully grown rabbits and the distribution pattern of plutonium in these animals has been compared with that in the weanling rabbits. Another group of seven-month-old rabbits has been given intrasmuscular injections of plutonium nitrate, and distributions have been compared with those in animals given intravenous injections. Intramuscular injection should provide a better comparison with the situation arising in human contamination, where plutonium can enter the body through wounds from contaminated glassware or instruments. It has often been assumed that with wounds, the plutonium remains localised at the site of entry and is excreted very slowly. This p...