Preliminary Studies of the Interaction between 239PuO2 and Cigarette Smoke in the Mouse Lung

Summary

Our current experiments were designed to show whether 12 months' exposure to cigarette smoke enhances the incidence of lung tumours in mice that had previously inhaled ²³⁹PuO₂. These periods of smoke exposure are almost complete. After death their lungs will be cleared and any nodules found will be sectioned for histopathology. This paper reports the results of two preliminary experiments conducted earlier.

The first study showed that mice could tolerate the proposed smoking regime for 3 months, with no sign of ill health in any animal throughout. The major difference found was a reduced growth rate in both smoke- and sham-exposed mice relative to that of cage controls. After 3 months of treatment, histopathology and morphometry of lung sections found only slight smoke-induced changes. These included a reduced proportion of alveolar space and an increased number of pulmonary alveolar macrophages (PAM) per unit area. Bronchopulmonary lavage showed that the PAM from smoke-exposed mice were larger than those from sham-exposed or control mice and that an increased proportion of cells were binucleate.

All mice in the second study were initially exposed to ²³⁹PuO₂, then subsequently divided into three treatment groups as above. Cigarette smoke exposure was shown to inhibit the removal of ²³⁹Pu from the lung whilst sham exposure had no effect. Smoke exposure also produced an increase and sham exposure a decrease in lung weights relative to those of cage controls. The latter was probably as a result of their lower growth rate. In our current experiments it is likely that the group receiving ²³⁹PuO₂, then smoke, will receive a higher radiation dose to lung than those receiving ²³⁹PuO₂ only. Any increased tumour incidence found will be considered in conjunction with this evidence.     

The Efficacy of DFO-HOPO,DTPA-DX and DTPA for Enhancing the Excretion of Plutonium and Americium from the Rat

Summary

A hydroxypridinone derivative of desferrioxamine (Na-DFO-HOPO), a dihydroxamic derivative of diethylenetriaminepenta-acetic acid (ZnNa-DTPA-DX), and DTPA (CaNa₃- and ZnNa₃-DTPA) were tested at dosages of 30 μmol kg^?1 for their ability to remove ²³⁸Pu or ²⁴¹Am from rats after their intravenous injection as citrate or inhalation as nitrate. The most effective treatment regimen for injected Pu was the repeated administration of DFO-HOPO; by 7 days the body content was reduced to 8% of that in untreated animals. Repeated dosages of 3 μmol kg^?1 DFO-HOPO were as effective as those of 30 μmol kg^?1 DTPA. After inhalation of Pu nitrate, repeated treatment with DTPA, DTPA-DX or DFO-HOPO reduced the body content by 7 days to, respectively, 10, 15 and 31% of those in untreated animals. After inhalation of Am, DTPA-DX and DTPA were equally effective, the body contents being reduced to 7% of control values with repeated treatment. Injection of DFO-HOPO was ineffective for enhancing the elimination of inhaled or injected Am. The results confirm the strategy of examining the use of siderophore analogues for the decorporation of Pu or Am. However, at present DTPA should remain the agent of choice, particularly after inhalation.     

Radiation Biology and Medicine

Young Beagle dogs were exposed by inhalation to aerosols of ²³⁹PuO₂ and observed for their lifespans as part of a large, ongoing study of the biological effects of inhaled radionuclides. The purpose of our study was to compare certain immune responses of the ²³⁹PuO₂-exposed dogs at middle age (7–10 years old) and old age (12–14 years old), with those of unexposed, age-matched or young (3–4 years old) animals. Some of the aged, exposed dogs had developed lung tumours. Lymphocyte proliferative responses to phytohaemagglutinin (PHA) were lower in aged control dogs than in either young or middle-aged control dogs. Both aged and middle-aged, radiation-exposed dogs had decreased responses to PHA when compared to age-matched controls. Responses to concanavalin A (Con A) were not affected by age in control dogs, but tended to decrease in the oldest group of radiation-exposed dogs. Responses to both PHA and Con A were severely depressed in tumour-bearing dogs. The cytolytic activity of natural killer cells was not affected by age, radiation exposure, or tumour presence. We concluded that inhalation of ²³⁹PuO₂ by young Beagle dogs resulted in an earlier-than-normal decrease in the ability of T cells to respond to mitogenic stimulation. In other words the depressed responses to PHA that were observed might represent radiation-induced, accelerated ageing of the T cell response.     

Comparative biokinetics of plutonium and americium after inhalation of PuO2 and mixed oxides (U, Pu)O2 in rat

PURPOSE: To compare the biokinetics of Pu and Am in rat after inhalation of PuO2 and two (U, Pu) mixed oxides (MOX), referred to as MIMAS and SOLGEL. MATERIALS AND METHODS: Lung clearance was measured in vivo by X-and y-ray spectrometry. Retention of Pu and Am in femurs, liver and kidneys was measured by alpha-spectrometry. RESULTS: Observed lung clearance was in the same range for all three powders. Extra-pulmonary transfers were expressed as the percent of the initial deep lung deposit (IDLD) measured 7 days after inhalation. After PuO2 exposure, bone retention remained nearly constant throughout the 270-day experiment. It was approximately 0.7% of the IDLD for Pu and Am. By contrast, a gradual increase was observed for the two MOX. After 7 days, bone retention of Pu and Am was respectively 0.05 and 0.08% for MIMAS, and 0.2 and 0.6% for SOLGEL. The retention reached maximal values between 180 and 270 days post-exposure, which were 0.2 and 0.3% for MIMAS, and 1.2 and 2.8% for SOLGEL for Pu and Am respectively. CONCLUSIONS: Different transfer rates of Pu and Am from the lung were observed depending on the chemical composition of the oxides and/or the method of their preparation.     

Long-term Changes in Mouse Lung Following Inhalation of a Fibrosis-inducing Dose of 239PuO2: Changes in Collagen Synthesis and Degradation Rates

Summary

Mice were exposed by nose-only inhalation to ²³⁹PuO₂, which resulted in an IAD of 1110 ± 29 Bq. At various times after exposure, rates of collagen metabolism were measured using validated in vivo methods based on the administration of radiolabelled proline, together with a large flooding dose of unlabelled proline and measurement of its incorporation into lung collagen as hydroxyproline. Dramatic increases in both synthesis and degradation rates of collagen were observed. At 54 days after exposure the fractional synthesis rates in experimental mice were almost five times those in controls (control: 3·2 ± 0·6%/day, ²³⁹PuO₂-exposed: 14·5 ± 0·4%/day) and by 300 days synthesis rates, although declining, were still more than double the control values. A similar pattern of change was observed for collagen degradation. The combination of changes in synthesis and degradation rates led to a 60% increase in lung collagen content by 300 days (control: 3·05 ± 0·24 mg/lung, ²³⁹PuO₂-exposed: 4·88 ± 0·42 mg/lung). The data suggest that extensive remodelling of the lung connective tissue matrix occurs during development of fibrosis and that, over long periods of time, small imbalances between synthesis and degradation may result in quite large increases in protein content.     

Efficacy of 3,4,3-LIHOPO for Enhancing the Excretion of Plutonium from Rat after Simulated Wound Contamination as a Tributyl-n-phosphate Complex

The siderophone analogue 3,4,3-LIHOPO, referred to hereafter as LIHOPO, has been examined for its ability to remove ²³⁸Pu in a tributyl-n-phosphate (TBP) complex from rat after intramuscular (i.m.) or subcutaneous (s.c.) contamination. The chelating agent was administered at a dosage of 30 µmol.kg^?1, 30 min after the contamination, either by intravenous (i.v.) or local injection. By day 7 after exposure, local (i.m.) administration of LIHOPO reduced the amounts of i.m.-injected ²³⁸Pu in the wound site, skeleton and liver to 75, 20 and 25% respectively of those in untreated animals. At the i.m. Pu wound site, local treatment was superior to i.v. treatment; both ligands were equally effective. At the s.c. Pu wound site, local and systemic treatments were equally effective and LIHOPO was superior to DTPA. After translocation, LIHOPO was the most effective treatment for enhancing Pu excretion, whatever the route of contamination and treatment: the administration of LIHOPO and DTPA reduced whole-body Pu retention by a factor 1·8 and 1·4 respectively. All these results are encouraging for the use of LIHOPO in the future but more studies are needed, concerning both the toxicity of the compound and its use in man.     

The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat: comparison with other siderophore analogues.

With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.     

Behaviour of spherical and irregular (U,Pu)O2 particles after inhalation or intratracheal instillation in rat lung and during in vitro culture with bovine alveolar macrophages

Spherical and irregularly shaped mixed (U,Pu) oxide particles were administered to rats by inhalation and by intratracheal instillation. The lung retention of the particles was independent of particle shape and of the route of administration. Only a small percentage of the administered radioactivity was found in other organs. Detailed electron microscopic studies showed particles within membrane-enclosed vacuoles as well as lying free in the cytoplasm.     

氧化亚氮吸入配合局麻对儿童埋藏牙拔除的效果观察

目的 观察氧化亚氮(笑气)吸入配合局麻对儿童埋藏牙拔除的效果。方法 选取儿童埋藏牙患者94例,分两组分别采取氧化亚氮吸入配合局部麻醉和单纯采用局部麻醉拔除。通过两组患者的心率变化,镇静程度差异及耐受与配合程度差异评定来评价氧化亚氮吸入配合局麻对儿童埋藏牙拔除的效果。结果 对照组患者拔牙前及拔牙中的心率明显高于实验组,且术前、中的镇静效果及耐受及配合程度明显减弱。结论 氧化亚氮吸入配合局麻具有安全、有效等特点,对于儿童埋藏牙拔除具有很好的辅助效应。     

Modelling of cell deaths and cell transformations of inhaled radon in homes and mines based on a biophysical and microdosimetric model

Purpose: In this study a biophysical mechanism-based microdosimetric model was applied to predict the biological effects of inhaled radon progenies in homes and in uranium mines.

Materials and methods: The radon daughter concentrations of more than 2000 homes were averaged in case of home exposure and the New Mexico uranium mine data were used in case of exposure in mines. The complex microdosimetric model applied in this work was developed by combining a computational fluid and particle dynamics (CFPD) lung model with a lung dosimetry model that quantify the local distribution of radiation burden and the Unit-Track-Length Model, which characterizes the biological outcome of the exposure.

Results: Our results show that the inhomogeneity of radon daughter deposition is stronger in the case of mines. Consequently, the numbers of cells which receive multiple hits and the maxima of radiation burdens are significantly higher in mines. In contrast to this, the distributions and maximum values of cell transformation probabilities are very similar in the two cases.

Conclusions: If the same amounts of inhaled progenies are considered then primary cellular consequences are very similar in case of homes and mines, however, the local maxima of radiation burden are higher in mines.     

Influence of intravenously administered lidocaine on cerebral blood flow in a baboon model standardized under controlled general anaesthesia using single-photon emission tomography and technetium-99m hexamethylpropylene amine oxime

The baboon under general anaesthesia as a model to assess drug-induced cerebral blood flow changes ( CBF) using single-photon emission tomography (SPET) offers great in vivo possibilities but has to comply with demands on control of anaesthesia-related influencing factors, such as P _aCO₂ changes. The model sought in this study and described here allows control of P _aCO₂, in the baboon under thiopentone anaesthesia by ventilation, and was evaluated for the functional dependence of CBF vs P _aCO₂, using SPET technetium-99m hexamethylpropylene amine oxime (HMPAO) and the split-dose method together with controlled ventilation. During the experiment the model was validated for normal reactivity to P _aCO₂ changes, and subsequently applied to investigate the mechanisms (still uncertain) of CBF increase known to follow administration of the local anaesthetic lidocaine. Six baboons received 6 mg/kg lidocaine intravenously. CBF was measured between two consecutive SPET acquisitions (split-dose method) respectively relating to HM-PAO distributions in the brain before and after the injection of lidocaine. Meanwhile the animals were maintained at constant respiratory rate and volume. The results indicate that the correlation between CBF and the ensuing fall in P_aCO₂ deviated from the baseline pattern from the model and confirmed a cerebrovascular contribution to the lidocaine-induced CBF increase. This agreed well with mean and systolic blood pressure changes and heart rate. Correspondence to: I.C. Dormehl     

Deposition of aqueous aerosol of technetium-99m diethylene triamine penta-acetic acid generated and delivered by a novel system (AERx) in healthy subjects

Deposition of technetium-99m diethylene triamine penta-acetic acid aqueous radioaerosols generated by a novel aerosol delivery system (AER_x) was studied in six healthy subjects using both planar and single-photon emission tomography (SPET) imaging. AER_x is a microprocessor-controlled, bolus inhalation device that is actuated at pre-programmed values of inspiratory flow rate and volume. The aims of the study were to determine the effects of posture and inhaled volume upon deposition of the aerosol in the lungs. Each subject inhaled the radioaerosol in two positions (supine vs sitting) and with two inspiratory manoeuvres [vital capacity (VC) vs ”fixed volume” of 1 l above functional residual capacity]. Simultaneous transmission-emission planar and tomographic images were acquired. The results showed diffuse deposition of the aerosol in the lung. Neither the breathing manoeuvre nor the posture was found to affect the distribution of the aerosol as measured by the ratio of the activity (counts per pixel) in the peripheral:central (penetration index, PI) or in the apex:base regions of the planar lung images (P>0.1). A small, albeit statistically significant, difference in PI (P<0.03) was found between VC and fixed volume sitting manoeuvres with SPET only. The PI values themselves indicate that the radioaerosol was well distributed in the lung, with the periphery having 45%–64% of the activity of the central region. Superposition of transmission SPET lung outline on emission SPET visually confirmed the excellent peripheral deposition of the aerosol. The AER_x system showed high efficiency of delivery, with approximately 50% of the extruded dose in the device depositing in the lung. The uniformity of radioactivity distributed throughout the lung is attributed to the fine particle size (mass median aerodynamic diameter of 2 μm) of the aerosol and the electronic control of aerosol inhalation by the device. In conclusion, the AER_x system can be ideal for diffuse aerosol deposition of therapeutic or diagnostic agents and is largely unaffected by inhaled volume and posture. The efficiency of the device device can limit the total radiation exposure of patients and staff administering the radioaerosols, and can make it suitable for delivery of expensive drugs. Received 6 October and in revised form 30 November 1998     

The efficacy of DFO-HOPO, DTPA-DX and DTPA for enhancing the excretion of plutonium and ameriicum from the rat.

A hydroxypridinone derivative of desferrioxamine (Na-DFO-HOPO), a dihydroxamic derivative of diethylenetriaminepenta-acetic acid (ZnNa-DTPA-DX), and DTPA (CaNa3- and ZnNa3-DTPA) were tested at dosages of 30 mumol kg-1 for their ability to remove 238Pu or 241Am from rats after their intravenous injection as citrate or inhalation as nitrate. The most effective treatment regimen for injected Pu was the repeated administration of DFO-HOPO; by 7 days the body content was reduced to 8% of that in untreated animals. Repeated dosages of 3 mumol kg-1 DFO-HOPO were as effective as those of 30 mumol kg-1 DTPA. After inhalation of Pu nitrate, repeated treatment with DTPA, DTPA-DX or DFO-HOPO reduced the body content by 7 days to, respectively, 10, 15 and 31% of those in untreated animals. After inhalation of Am, DTPA-DX and DTPA were equally effective, the body contents being reduced to 7% of control values with repeated treatment. Injection of DFO-HOPO was ineffective for enhancing the elimination of inhaled or injected Am. The results confirm the strategy of examining the use of siderophore analogues for the decorporation of Pu or Am. However, at present DTPA should remain the agent of choice, particularly after inhalation.     

Effectiveness of DTPA treatments following the injection of particulate plutonium.

A limited long-term experiment has been completed in which the chronic toxicity resulting from a single intravenous injection of 31.4 kBq of a poly-disperse 239Pu colloid sol per kg of body weight was tested in Beagle dogs. The Pu deposited mostly in the phagocytic cells of liver, spleen and to a lesser degree in lung and bone marrow. Slow solubilization of the Pu particles by endogenous ligands caused translocation of the nuclide and redeposition mostly as monomeric Pu in the skeleton and in liver hepatocytes. Thus, the deposit behaved as expected from a pulmonary or wound contamination in humans with a moderately soluble depot of Pu such as Class W hot particles. Therefore, this type of deposit provided the basis for a practical model to study the ensuing radiation effects under various experimental conditions. The dogs were divided into three groups of four animals each, and the following conditions were applied: (a) no further treatment was given, allowing free translocation of the Pu to its secondary deposition sites; (b) interception of the Pu translocation by weekly injections of 30 mumol of Ca-DTPA/kg of body weight (Ca-chelate of diethylene-triaminepentaacetic acid); and (c) interception of translocation by daily injections of 30 mumol/kg body weight of Zn-DTPA. For each of the groups (b) and (c), three dogs were used in a lifetime study, and one was sacrificed for nuclide distribution studies. Free translocation and subsequent deposition in the skeleton resulted in the death of each of the non-chelated dogs from osteosarcoma between 1267 and 1594 days after injection. Weekly treatment with Ca-DTPA reduced the total Pu burden significantly, but these dogs also died with osteosarcoma between 1462 and 1783 days. Daily injections with Zn-DTPA reduced the total Pu burden more efficiently than Ca-DTPA and prevented continuous deposition of solubilized Pu on bone surfaces. The mean post-injection survival of these dogs was 3520 days or about 2.1 times that of the animals receiving Ca-DTPA, while the latent period for bone tumour induction was about 2.6 times longer. This treatment reduced the severity of liver lesions and eliminated the occurrence of persistent leukopenia, but it did not prevent the formation of bone cancer.     

Comparative absorption parameters of Pu and Am from PuO2 and mixed oxide aerosols measured after in vitro dissolution test and inhalation in rats

PURPOSE: To compare specific absorption parameter values obtained from in vitro dissolution studies (this paper) and in vivo experiments (data published by Ramounet et al, 2000) and to determine their influence on Dose Per Unit Intake (DPUI) calculations. MATERIALS AND METHODS: Experiments were performed on plutonium oxide (PuO2) and two Mixed Oxide (MOx) preparations containing 5% Pu (w/w) made according to the industrial process in vitro using a static test and in vivo after rat inhalation. RESULTS: Behaviour of Pu and Am shows, in vitro, at shorter times, a greater rapid dissolution fraction f(r) for Pu (factor 10) and Am (factor 2) with MOx powders compared with PuO2, whereas in vivo results show a greater fraction f(r) for Pu (factor 5) and Am (factor 15) with PuO2 compared with MOx powders. This phenomenon has not been observed for slow dissolution absorption parameter s(s). The in vivo parameters for Pu and Am in these materials were very close to the default values recommended by International Commission for Radiological Protection for default Type S. CONCLUSIONS: Results obtained have shown that solubility of Pu from the mixed oxide was higher than that of Pu from PuO2. Nevertheless, no significant difference was observed between the three compounds in the corresponding dose coefficients in vivo or in vitro. Therefore, for these particular compounds, variation in the chemical composition of the aerosols had no significant influence on DPUI. Consequently, in vitro, the dissolution test can provide a good estimate of the in vivo behaviour. Studies of variation of % Pu (w/w) from MOx are in progress in our laboratory to confirm these conclusions.     

双向腔肺动脉吻合术后肺血流灌注不足患儿吸入NO的疗效观察

目的探讨双向腔肺动脉吻合术(BCPS)术后肺血流灌注不足患儿吸入一氧化氮(NO)的疗效。方法采用美国Ohemda公司NO吸入治疗仪,通过呼吸机吸入NO 2.5~20.0/百万,监测血流动力学和呼吸功能指标,定期监测NO2、高铁血红蛋白(MetHb)含量。结果吸入NO后,中心静脉压,跨肺压,肺泡-动脉氧分压差,呼吸指数降低(P<0.01);动脉血氧饱和度,动脉血氧分压与吸入氧浓度之比上升(P<0.01)。NO2和MetHb含量分别为(0.1±0.2)百万和(1.1±0.3)%,均在安全范围内。术后3 d复查血小板为(231±84)×109/L,未出现血小板减少。术后近期并发低氧血症20例,其中18例改善;低心输出量综合征(低心排)4例;2例颜面部水肿、8例上半身水肿,均改善。术后24 h内再手术4例(由全腔肺动脉吻合术改为双向腔肺动脉吻合术)。死亡2例,病死率5%,死亡原因为低心排、低氧血症。结论外源性吸入NO用于BCPS术后肺血管阻力暂时性增高的患儿,可改善其肺血流灌注和氧合功能,减少低心排的发生,是一种安全且有效的选择性肺血管扩张剂。     

Survival,lung clearance,dosimetry and gross pathology of rats exposed to either NpO 2 or PuO 2 aerosols

Purpose : To compare survival, lung dosimetry and gross pathology after inhalation exposure of rats to either NpO 2 or industrial PuO 2 aerosols with similar granulometric parameters. Because the specific alpha activity ratio Pu/Np is about 600, a much more homogeneous lung irradiation was expected for NpO 2. Materials and methods : Male Sprague Dawley rats were exposed once and their lung burdens were measured by X-ray spectrometry at different times post-exposure up to death. The time-course of doses delivered to the lungs were estimated, taking into account individual lung clearance parameters and body and lung weights. Gross lung pathologies were scored at autopsy. Results : In the range of initial lung deposits (ILD) studied (0.1-4 kBq), lung clearance impairment and reduced lifespan were only observed after exposure to NpO 2. For similar ILD or doses, the highest incidences of lung lesions assumed to be tumours were observed for NpO 2 with a saturation of lung tumour induction for doses larger than 8 Gy (ILD: 1.5kBq). Up to 22Gy (ILD: 3.5kBq), such saturation was not observed for PuO 2. Conclusions : NpO 2 appears much more toxic than PuO 2. Before saturation, lung tumour incidence increased nearly linearly with dose, the slope of the curve for NpO 2 being about twice as steep as that for PuO 2     

Survival, lung clearance, dosimetry and gross pathology of rats exposed to either NpO2 or PuO2 aerosols

PURPOSE: To compare survival, lung dosimetry and gross pathology after inhalation exposure of rats to either NpO2 or industrial PuO2 aerosols with similar granulometric parameters. Because the specific alpha activity ratio Pu/Np is about 600, a much more homogeneous lung irradiation was expected for NpO2. MATERIALS AND METHODS: Male Sprague Dawley rats were exposed once and their lung burdens were measured by X-ray spectrometry at different times post-exposure up to death. The time-course of doses delivered to the lungs were estimated, taking into account individual lung clearance parameters and body and lung weights. Gross lung pathologies were scored at autopsy. RESULTS: In the range of initial lung deposits (ILD) studied (0.1-4 kBq), lung clearance impairment and reduced lifespan were only observed after exposure to NpO2. For similar ILD or doses, the highest incidences of lung lesions assumed to be tumours were observed for NpO2 with a saturation of lung tumour induction for doses larger than 8 Gy (ILD: 1.5kBq). Up to 22Gy (ILD: 3.5kBq), such saturation was not observed for PuO2. CONCLUSIONS: NpO2 appears much more toxic than PuO2. Before saturation, lung tumour incidence increased nearly linearly with dose, the slope of the curve for NpO2 being about twice as steep as that for PuO2.     

大鼠吸入贫铀气溶胶后体内铀的分布

目的 建立贫铀(depleted uranium, DU)气溶胶吸入动物模型,观察气溶胶吸入后DU在重要组织器官的蓄积情况。方法 采用大鼠吸入DU气溶胶的实验模型,分别在吸入后的30、90、180、270、360和540 d,采用激光时间分辨发光分析法测定肺脏、肾脏、股骨、肝脏、心脏、脑、脾脏和胸腺等的铀含量。结果 DU气溶胶吸入后高低剂量组大鼠肺铀含量分别为(499 833.3±14 214.8)ng/g及(25 424.0±6193.4)ng/g,明显高于未吸入组(28.8±13.9)ng/g (P<0.05)。吸入30 d后,肺、股骨及肾中的铀含量明显升高,随时间逐渐下降;吸入60d起,肝脏、大脑、心脏、胸腺、脾脏中铀含量高于对照组,铀含量呈先升高后降低的两相分布。铀含量以肺脏、股骨、大脑、胸腺中较高,肾次之,肝、心脏、脾较少。结论 DU气溶胶吸入后,铀可在肺、肾、股骨、肝脏、大脑、心脏、胸腺、脾脏等分布,其中肺、股骨、大脑、胸腺及肾脏中高浓度铀的存在提示上述器官是DU损伤的潜在靶器官。     

The Incorporation of Plutonium by the Embryo and Fetus of Rats and Guinea-pigs

Summary

The transfer of ²³⁸Pu from the maternal circulation to the developing embryo and fetus was studied in rats and guinea-pigs to provide data for the development of dosimetric models for the human embryo and fetus. Following administration at different stages of gestation, measurements were made after 3 days in the rat and 7 days in guinea-pigs. The amount transferred was greater after administration at later stages of gestation, up to a maximum of about 0·8–0·9% of the injected activity per fetoplacental unit (FPU) and about 0·2% per fetus in both species. In advanced gestation the yolk sac, the initial site of haemopoietic stem cells, contained up to 80% of the total activity in the FPU in rats, compared with about 25% for the guinea-pig; retention in placental trophoblast was greater in the guinea-pig. The concentrations of ²³⁸Pu in the yolk sac were generally about two to three orders of magnitude greater than fetal concentrations and of the same order as in maternal liver and bone. In both species, concentrations in the embryo and fetus were greatest after injection early in gestation, reached their lowest around mid-organogenesis and increased again in later gestation. The fetus:mother whole-body concentration ratios in late gestation were about 0·1 and 0·05 in rats and guinea-pigs, respectively. Measurements were also made of the ²³⁸Pu retention in neonates at birth. In guinea-pigs the liver accounted for about 6–9% of retained activity; similar values for femora indicated skeletal retention of about 60–80%. For administration at each stage of gestation, and particularly at early stages, transfer of ²³⁸Pu to the fetus continued throughout gestation but concentrations decreased due to fetal growth.