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.     

Local distribution and dosimetry of 226Ra in the trabecular skeleton of the beagle.

Young adult beagle dogs received a single injection of 38.1 kBq/kg body wt 226Ra and were serially sacrificed at 4 to 2955 days postinjection. Samples of sites of trabecular bone in the lumbar vertebral body, proximal ulna, and distal femoral metaphysis and epiphysis were analyzed autoradiographically. The time-dependent changes in the average 226Ra concentrations in the four regions were analyzed in terms of a compartmental model. The clearance rate from the lumbar vertebral body was about four times more rapid than for the proximal ulna and distal femoral epiphysis. Ratios of hotspot to diffuse label concentrations varied from about 10 to 23. The dose rate to the endosteum ranged between 8.7 and 39.5 mGy/day initially and 4 and 10.5 mGy/day toward the end of the observation period. Mean marrow dose rates were lower by a factor of 3 to 9.5. During their residence time the nuclei of bone lining cells receive a maximum dose of 8 Gy in the proximal ulna (2955 days after injection) and a minimum dose of 0.63 Gy in the lumbar vertebra (2955 days after injection). This corresponds on the average to 17 and 1.4 alpha-particle hits to the cell nuclei, respectively.     

Retention and dosimetry of injected 241Am in beagles

Equations have been derived, from the results of total-body and partial-body counting and gamma-ray counting of individual bones and soft tissues, which describe the retention of injected 241Am in the liver, in the nonliver tissue (including skeleton), and in the skeleton of young adult beagles. Retention was found to be dependent upon injection level, and different sets of equations were developed for dogs given about (a) 2.8 microCi/kg (b) 0.9 microCi/kg (c) 0.3 microCi/kg, and (d) 0.1 microCi/kg and less. Liver rention, RL, was characterized by a single exponential equation of the form RL = ce-beta t, with c = 0.49 +/- 0.04 and beta = a function of injection level. Nonliver tissue was assigned a retention equation of the form RNL = d + alpha + J(l - e-mt), with d = 0.102 +/- 0.024 e-1.22t, alpha = 0.41 +/- 0.04, and both J and m as a function of injection level. Skeletal retention was found to be about 0.885 +/- 0.037 of nonliver retention with no significant dependence upon either injection level or time after 241Am injection. Dosimetry equations based on these retention expressions were derived. Individual bones of 55 beagles were assayed at death for their 241Am content for a determination of 241Am distribution within the skeleton.     

The activity ratio of 228Th to 228Ra in bone tissue of recently deceased humans: a new dating method in forensic examinations

Reliable determination of time since death in human skeletons or single bones often is limited by methodically difficulties. Determination of the specific activity ratio of natural radionuclides, in particular of 232Th (Thorium), 228Th and 228Ra (Radium) seems to be a new appropriate method to calculate the post mortem interval. These radionuclides are incorporated by any human being, mainly from food. So with an individual's death the uptake of radionuclides ends. But the decay of 232Th produces 228Ra and 228Th due to its decay series, whereas 228Th is continuously built up in the human's bones. Thus, it can be concluded that in all deceased humans at different times after death different activity ratios of 228Th to 228Ra will develop in bone. According to this fact it should be possible to calculate time since death of an individual by first analysing the specific activities of 228Th and 228Ra in bones of deceased and then determining the 228Th/228Ra activity ratio, which can be assigned to a certain post-mortem interval.     

Toxicity of 241Am in male C57BL mice: relative risk versus 226Ra

A life-span study on male C57BL mice after injection of various doses of 241Am was conducted. The effects on life span were evaluated and the incidence of tumors was determined by procedures that take competing risks into account. Bone tumors were induced in the mice by injections of 22 and 58 Bq 241Am per g. The mice died early from nonneoplastic diseases at the higher dose levels (190, 373, and 1197 Bq 241Am/g). Additionally, spontaneously occurring tumors such as liver carcinomas, lymphosarcomas, and lymphoreticulosarcomas occurred at an enhanced rate with increasing dose level. The data for survival time after 241Am injection and death with bone tumor were compared to data collected previously for 226Ra-injected mice of the same C57BL strain. This enabled direct comparison in the same strain of the effects of the bone-surface seeker 241Am to the effects of the bone-volume seeker 226Ra. The proportional hazards model was applied and the rate of death with bone tumor was 12.9 +/- 5.2 times higher after 241Am injection than after 226Ra injection if the regression covariate was the average dose to the skeleton. The relative risk was 3.5 +/- 1.7 if regressed on the injected radioactivity. The mortality rate after 241Am injection was 20.4 +/- 3.6 times higher than after 226Ra injection if regressed on average dose to the skeleton.     

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.     

Estimates of microcurie-days residence,bone dose equivalent,and (MPC)W for thorium-232 in man using a mammillary model

A four-compartment mammillary model for the distribution and excretion of thorium and its daughter radium is studied and applied to the problem of estimating the radiation dose to organs and tissues of man for the case of a single intake of²³²Th. The long-lived daughter²²⁸Ra (∼6 y) grows in with time and gives birth to the other short-lived daughters (<0.4 day) which irradiate those tissues in the vicinity of their point of production. Some data on²²⁸Th and its daughter²²⁴Ra are available on dogs from which a model is derived and tested. Then, from some single-intake data (Th and Ra) on man, parameters for the model are estimated and estimates of residence times of the²³²Th daughters in man are made. Also, the 50-year radiation dose (dose equivalent) to bone from a single intake of²³²Th is estimated. Research sponsored by the U.S. Atomic Energy Commission under contract with Union Carbide Corporation.     

Distribution of 239Pu in the skeleton of the tree shrew (Tupaia belangeri) between 15 and 50 months after injection

The macroscopic and microscopic distribution of intramuscularly injected, essentially monomeric, 239Pu was studied in the skeleton of the adult tree shrew (Tupaia belangeri). Data for the period between 15 and 50 months after injection are presented and compared with the data from earlier time points. Between 83 and 500 days after injection the nuclide content and the wet weight of the skeleton decreased to a constant level at about 55 per cent of the maximum values. The microscopic distribution has been analysed in distal femora, proximal humerus, proximal tibia and lumbar vertebra over the whole observation time; additionally at some selected time points proximal femur, femur shaft, distal humerus and distal tibia were analysed. The initial endosteal surface activity ranged from 3.8 to 5.3 Bq/cm2 and decreased to a minimum at about 1000 days after injection and increased thereafter. A similar behaviour was found for the dose rate near bone surfaces which was initially about 0.075 Gy/day on endosteal surfaces. In the deep bone and the deep marrow the dose rate was negligible, about 0.008 Gy/day and 0.001 Gy/day, respectively. The average cumulative dose 1500 days after injection was about 67 Gy on the endosteum, six times greater than the cumulative dose calculated from the mean concentration of plutonium in the whole skeleton. All values are normalized to an injected activity of 37 kBq/kg body weight. The tupaia data are discussed in relation to the available data from monkeys, dogs and rats.     

高原鼢鼠和高原鼠兔骨骼中非必需微量元素的测定

铅、镉、砷、汞、锑和铋等元素是人与动物生命活动非必需且有害的微量元素[1] 。哺乳类动物体内的这些微量元素主要由食物链传递所产生[2 ,3] 。本文对高原鼢鼠 (Ｍｙｏｓｐａｌａｘｂａｉｌｅｙｉ)和高原鼠兔(Ｏｃｈｏｔｏｎａｃｕｒｚｏｎｉａｅ)骨骼中非必需微量元素砷、锑、汞、铋、铅、镉的分布、种间含量差异及其相关性进行了分析和讨论 ,为高寒草甸生态系统研究小哺乳动物的营养生态学、化学生态学以及生态系统的物质循环[4 ,5] 等提供基础资料。1　材料与方法1 1　样品预处理1994年 5～ 6月在中国科学院海北高寒草甸生态系统定位站…     

Radium - 226 retention in placenta and whole body of rat

The 226Ra retention in the placenta of rat during 3 successive pregnancies (92-213 days after injection) was about 4-5 x 10(-3)% of the injected dose (ID) constituting nearly 0.009% of the whole body 226Ra content (45-55% ID) in each pregnancy. Thus a uniform relationship was being displayed between the two contents to a reasonable extent. The implication of this observation is discussed vis-a-vis the determination of Ra body burden.     

Radiation risk assessment for plant reference species (Pinus sylvestris and Vicia cracca) from the area of radium production waste storage

The risk of an enhanced level of radionuclides of the uranium and thorium decay series in the environment for reference plant species (Pinus sylvestris and Vicia cracca) was assessed. 238U, 230Th, 226Ra, 210Po, 232Th and 228Th concentration factors for plants were found to be lower than one. The aboveground parts of Vicia cracca sampled from the area of the radium production waste storage mainly accumulated 22Ra, Pinus sylvestris branches--210Pb, 226Ra and 210Po. LOEDR calculated for the chromosome aberration frequency in both plant studies was 17-71 microGy/h. LOERD values for the reproductive capacity decrease in P. sylvestris and V. cracca were 17-71 microGy/h and 116-258 microGy/h, correspondingly. EDR10 for the chromosome aberration frequency in P. sylvestris and V. cracca were 148 and 347 microGy/h, that is, correspondingly, 255 and 708 times higher that background values. EDR10 for the plant reproductive capacity was 11-34 microGy/h, which 19-69 times increases the background values.     

Bone structural parameters, dosimetry, and relative radiation risk in the beagle skeleton

A variety of morphometric and histomorphometric parameters such as the mass of bone and marrow, bone surface areas, percentage of bone volume, percentage of the surface that is trabecular, and percentage of surfaces that are forming and resting are calculated for all major parts of the beagle skeleton. The total bone surface of the beagle is estimated at 2.9 m2 with 53.7% of the surface area being associated with trabecular bone. There are about 4.5 x 10(9) bone-lining cells and about 1 x 10(9) osteoblasts. From the fractional retention in each part of the skeleton, the initial surface concentration of 239Pu after a single injection of 592 Bq/kg body wt (0.016 microCi/kg) on resting surfaces and at sites of bone formation is calculated for various values of the affinity ratios of trabecular/cortical and forming/resting surfaces. These estimated concentrations then yield dose rates as well as cumulative and collective doses to bone-lining cells and osteoblasts in the different parts of the skeleton. On the assumption that the relative risk of tumor induction is proportional to the collective dose to either bone-lining cells or osteoblasts, the frequency of tumor occurrence is calculated and compared to observed frequencies. Both hypotheses yield approximate agreement with experimental data for different ratios of trabecular/cortical radiation sensitivity, although the differences between some bones are statistically significant.     

Localization of bismuth radiotracer in rat kidney following exposure to bismuth

It has been proposed that alpha emitting 212Bi (t1/2 = 60 min) coupled to tumor-specific antibodies may be a useful radiotherapeutic agent. However, since Bi can accumulate in the kidney, it is necessary to characterize the factors influencing localization of Bi within this tissue in order to evaluate the potential for radiation damage to the renal system. In this study, the localization of Bi radiotracers was determined in kidneys of rats previously exposed and not exposed to mumole quantities of Bi. Following repeated injection of Bi (4 x 14 mumols (3 mg Bi)/kg bw) the element accumulated mainly in the kidney followed by liver, spleen, pancreas, bone, and brain. Kidney copper and liver zinc concentrations were higher in Bi-exposed rats than in non-exposed rats. Within the cytosol, in Bi-exposed rats, Bi radiotracer in the kidney was associated with a metallothionein-like protein (Mt). In contrast, non-exposed rats contained no detectable metallothionein-like proteins in the kidney and the Bi tracer was associated with the hemoglobin fraction of the cell. Thus, when Bi is administered in tracer quantities such as that incorporated for use as a radiopharmaceutical, no induction of, and association with, metallothionein-like proteins should occur. These results suggest that the potential nephrotic effects of 212Bi will be influenced by the individual's previous exposure to Bi-containing drugs, or other metallothionein-inducing insults.     

Microdistribution and local dosimetry of 226Ra in trabecular bone of the beagle

Sections of lumbar vertebral bodies of young adult beagle dogs have been analyzed autoradiographically to characterize and quantify the local distribution of 226Ra by means of a scanning microscope photometer. The animals received a single injection of 355 kBq/kg body weight and were serially sacrificed at 5 to 1381 days postinjection. Hotspot concentrations decreased from about 51 kBq/g bone at 5 days to 20 kBq/g at 1381 days postinjection. The diffuse concentration changed from 8.3 to 1.9 kBq/g. The mean 226Ra concentration in the trabecular areas scanned was initially higher and at the end of the observation period lower than the average calculated for the whole lumbar vertebral column. Density and area of, and fraction of bone activity in, hotspots virtually remained constant. With time hotspots tended to become translocated into bone volume. Mean dose rates to lining cells from both hotspots and diffuse labels decreased from about 210 mGy/d at early postinjection times to 105 mGy/d. This corresponds to 2.5 to 1.1 times the average skeletal dose rate. A discussion of the level of irradiation in terms of hit frequencies shows that osteoblasts in the initial phase of hotspot formation receive about 60 hits to their nucleus for the duration of bone formation. After about 6 months, however, the 226Ra concentration in new bone and the corresponding hit frequency appears to be low enough that interference with bone formation is unlikely. Morphometric measurements showed that abnormal bone accretion and thickening of trabeculae occurred. This was interpreted as an imbalance between bone formation and resorption. Both formation and resorption seem to be substantially lowered compared to control animals.     

Requirement of B7 costimulation for Th1-mediated inflammatory bone resorption in experimental periodontal disease

The CD28 costimulation at TCR signaling plays a pivotal role in the regulation of the T cell response. To elucidate the role of T cells in periodontal disease, a system of cell transfer with TCR/CD28-dependent Th1 or Th2 clones was developed in rats. Gingival injection of specific Ag, Actinobacillus actinomycetemcomitans 29-kDa outer membrane protein, and LPS could induce local bone resorption 10 days after the transfer of Ag-specific Th1 clone cells, but not after transfer of Th2 clone cells. Interestingly, the presence of LPS was required not only for the induction of bone resorption but also for Ag-specific IgG2a production. LPS injection elicited the induction of expression of both B7-1 and B7-2 expression on gingival macrophages, which otherwise expressed only MHC class II when animals were injected with Ag alone. The expression of B7 molecules was observed for up to 3 days, which corresponded to the duration of retention of T clone cells in gingival tissues. Either local or systemic administration of CTLA4Ig, a functional antagonist of CD28 binding to B7, could abrogate the bone resorption induced by Th1 clone cells combined with gingival challenge with both Ag and LPS. These results suggest that local Ag-specific activation of Th1-type T cells by B7 costimulation appeared to trigger inflammatory bone resorption, whereas inhibition of B7 expression by CTLA4Ig might be a therapeutic approach for intervention with inflammatory bone resorption.     

Rapid loss of bone mass and strength in mice after abdominal irradiation

Localized irradiation is a common treatment modality for malignancies in the pelvic-abdominal cavity. We report here on the changes in bone mass and strength in mice 7-14 days after abdominal irradiation. Male C57BL/6 mice of 10-12 weeks of age were given a single-dose (0, 5, 10, 15 or 20 Gy) or fractionated (3 Gy × 2 per day × 7.5 days) X rays to the abdomen and monitored daily for up to 14 days. A decrease in the serum bone formation marker and ex vivo osteoblast differentiation was detected 7 days after a single dose of radiation, with little change in the serum bone resorption marker and ex vivo osteoclast formation. A single dose of radiation elicited a loss of bone mineral density (BMD) within 14 days of irradiation. The BMD loss was up to 4.1% in the whole skeleton, 7.3% in tibia, and 7.7% in the femur. Fractionated abdominal irradiation induced similar extents of BMD loss 10 days after the last fraction: 6.2% in the whole skeleton, 5.1% in tibia, and 13.8% in the femur. The loss of BMD was dependent on radiation dose and was more profound in the trabecula-rich regions of the long bones. Moreover, BMD loss in the total skeleton and the femurs progressed with time. Peak load and stiffness in the mid-shaft tibia from irradiated mice were 11.2-14.2% and 11.5-25.0% lower, respectively, than sham controls tested 7 days after a single-dose abdominal irradiation. Our data demonstrate that abdominal irradiation induces a rapid loss of BMD in the mouse skeleton. These effects are bone type- and region-specific but are independent of radiation fractionation. The radiation-induced abscopal damage to the skeleton is manifested by the deterioration of biomechanical properties of the affected bone.     

220-Rn retention in mouse bone

Conclusions The experiment has shown that about half of the²⁰⁰Rn produced from²²⁴Ra in mouse bone escapes before decay in the period up to 8 days following injection. It is expected that the radiation dose delivered to structures within bone will be reduced in consequence.     

The metabolism of radium-226 during pregnancy in the rat

Metabolism of radium including the transfer to the fetus through the placenta was studied during three successive pregnancies 92, 155, and 213 days after injection of 226Ra in young female rats. The cumulative fecal and urinary excretions of 226Ra in a 213-day period following injection were about 30 and 15% injected dose (%ID), respectively, most of them occurring during the first 42 days. The excretions were similar in both the pregnant and control (unmated) rats. The whole-body burden of radium (mostly in the skeleton) determined by actual analysis of the entire body was similar in the two groups and was about 53, 48, and 44 %ID at the first, second, and third pregnancy, respectively. Pregnancy alone, therefore, did not significantly affect metabolism of radium. At 20 days of gestation the mean placental content of radium was 0.005, 0.0045, and 0.0036 %ID in the first, second, and third litter, respectively; the corresponding mean fetal content was 0.01, 0.008, and 0.005 %ID. The radium burden of the full-term neonate (21-22 days) was 0.014 and 0.011 %ID for the first and second delivery, respectively. The total amount calculated of radium transferred from the mother to the 8-10 fetuses in a litter did not exceed about 0.3% of the maternal content per each pregnancy. Comparison of the ratio of radium and calcium in the fetus and maternal skeleton shows that there is a Ra-Ca discrimination during their passage from the mother to the fetus.     

The dosimetry of 224Ra in mouse bone

Calculations are described, based on experimental findings, which show the variation of absorbed dose from 224Ra in bone marrow of CBA/H mice. These calculations indicate that, following an injection of a leukaemogenic amount of 16 kBq 224Ra into these mice, most marrow cells in the cancellous bone of femur ends are killed but most marrow cells in the femur shaft survive. The calculations also suggest that the mean leukaemogenic absorbed dose of about 1.5 Gy is received by a population of marrow cells about 30 microns from bone surface in the femur shaft.     

Effect of age on the efficacy of Zn-diethylenetriaminepentaacetic acid therapy for removal of Am and Pu from beagles

Decorporation of intravenously injected monomeric 241Am and 237+239Pu by the administration of 30 mumole Zn-diethylenetriaminepentaacetic acid (DTPA)/kg each day beginning 2 weeks after radionuclide injection was compared in beagles entered into the experiment when 3 months (juveniles). 1.9 years (young adults), or 10 years (mature adults) old and studied for about 5 months. DTPA therapy was most effective in the juvenile dogs and least effective in the mature adults. Retention of 241Am in the liver decreased from a pretreatment value for adults of about 50% of the injected activity to about 10% in the mature adults and less than 1% in the young adults at 140 days of treatment, while the liver retention of juveniles decreased from pretreatment values of about 16% to undetectable levels by 28 days of treatment. Plutonium retention in the liver decreased from adult pretreatment levels of about 30% of the injected activity (corrected for radioactive decay) to near 10% in the mature adults and 6% in the young adults at 140 days of treatment, while juvenile liver retention decreased from pretreatment values near 15% to undetectable levels by 56 days of treatment. Nonliver Am retention (mainly skeleton) decreased in mature adults from pretreatment values of about 45% of the injected activity to near 25%, in young adults from 35 to 20%, and in juveniles from roughly 70 to 9% by 140 days of DTPA administration. Nonliver Pu retention decreased from pretreatment values of about 50% of the injected activity (corrected for radioactive decay) for mature and young adults to about 30% by 140 days and from 75 to 16% in juveniles over the time period.