Urinary uranium and kidney function parameters in professional assistance workers in the Epidemiological Study Air Disaster in Amsterdam (ESADA).

BACKGROUND: The Epidemiological Study Air Disaster in Amsterdam (ESADA) aimed to assess long-term health effects in professional assistance workers involved in the 1992 air disaster in Amsterdam. As part of ESADA indications of nephrotoxicity due to exposure to uranium from the balance weights of the crashed aircraft were assessed. METHODS: Data of a historically defined cohort of 2499 (exposed and non-exposed) firefighters, police officers and hangar workers were collected 8.5 years after the disaster. Urinary uranium concentrations were determined by sector field inductively coupled plasma mass spectrometry. Urine albumin-creatinine ratio and fractional excretion of beta(2)-microglobulin were calculated from a single-spot urine specimen and simultaneous blood sample. Exposed assistance workers were compared with their non-exposed colleagues, and associations between uranium and kidney function parameters were explored. RESULTS: Median uranium concentrations were around 2 ng/g creatinine. Median values of albumin-creatinine ratio and fractional excretion of beta(2)-microglobulin were well below the level for microalbuminuria and for tubular damage, respectively. No statistically significant differences between exposed and non-exposed workers were found in uranium concentrations and kidney function parameters, although exposed hangar workers had lower uranium concentrations. No statistically significant associations were found between uranium concentrations and kidney function parameters in the total cohort. CONCLUSIONS: Occupational exposure to the air disaster in Amsterdam was neither significantly associated with higher uranium concentrations, nor with disturbed kidney function parameters. In this large cohort of professional assistance workers, urinary uranium concentrations were in the low range compared with previously published reference populations. No indications of nephrotoxicity were found at urinary uranium concentrations around 2 ng/g creatinine.     

Deaths from Neoplasms and Detection of Radionuclides in Excised Human Lungs in the Eordea Basin,Greece

Lignite contains various trace-metal natural radioactive contaminants. In the Eordea Basin, the most important lignite field in Greece, the authors conducted a proportional mortality ratio (PMR) study that compared the mortality rates of individuals who lived in the basin vs. a control group who resided in the city of Kilkis, over a 30-yr period. The following information was used in the study: (a) municipal registrations of deaths from neoplasms during the period from 1971 to 2000, and (b) detection of radioactive substances in samples obtained from excised lungs of individuals living in Eordea Basin who suffered from neoplasm. The corresponding registrations of deaths from neoplasm of the inhabitants of Kilkis, a city located outside the Eordea Basin, formed the control group. A diachronic increase of the PMR was detected as a result of neoplasms and, particularly, as a result of lung cancer in Eordea Basin. However, the above ratio did not exceed the corresponding PMR recorded in Kilkis. In 20 lung samples obtained from patients who had lived in Eordea Basin, and in 19 lung samples from patients in Kilkis, the activity of the radionuclides of uranium and thorium radioactive decay series, potassium-40, and cesium-137 was not higher than expected. No statistically significant difference was found between the inhabitants of the 2 regions, thus it was concluded that the increase in respiratory-system neoplasms was likely associated with the high prevalence of smoking among the regions' inhabitants. In future studies, a longer observation period and examination of more cases will be necessary to further investigate a possible association between radionuclides and lung neoplasms in the Eordea Basin.     

Molecular analysis of hprt mutations generated in Chinese hamster ovary EM9 cells by uranyl acetate, by hydrogen peroxide, and spontaneously

Naturally occurring uranium and depleted uranium (DU) are believed to be health hazards by virtue of both their chemical and radiological properties. The mechanism(s) behind uranium's chemotoxic effects has yet to be elucidated. Previous work has shown that DU, as uranyl acetate (UA), was mutagenic at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus in XRCC1-deficient CHO EM9 cells. The purpose of the current study was to characterize the mutations induced by UA at the hprt locus of CHO EM9 cells and compare the mutation spectrum of UA with those of hydrogen peroxide and spontaneous mutations in the same line. The hypothesis being tested was that if DU as UA is chemically genotoxic then the mutation spectrum induced by the heavy metal should be distinct from that produced spontaneously or by H2O2. A total of 59 UA-induced, 38 spontaneous, and 45 H2O2-induced mutations were identified. Base substitutions comprised 29%, 42%, and 16% of UA, spontaneous, and H2O2 mutants, respectively. The frequency of G --> T or C --> A substitutions was not significantly different in spontaneous or H2O2-induced mutants than in UA-induced mutants, suggesting a possible role for 8-oxodG damage in UA mutagenesis. However, the observation that UA produced significantly more major genomic rearrangements (multiexon insertions and deletions) than occurred spontaneously suggests the possibility that DNA strand breaks or crosslinks could also be UA-induced mutagenic lesions. The unique mutation spectrum elicited by exposure to UA suggests that UA generates mutations in ways that are different from spontaneous and free radical as well as radiological mechanisms.     

贫铀对大鼠肺诱导型一氧化氮合酶基因表达的影响

目的通过研究贫铀(depleted uranium,DU)颗粒气管灌注大鼠肺中的诱导型一氧化氮合酶(iNOS)基因表达的变化,揭示DU对肺组织的毒性作用机制。方法Wistar大鼠20只随机分为4组,1个对照组,3个染铀组,剂量分别为1、3、5 mg/ml气管灌注不同剂量DU颗粒3个月后,将大鼠肺组织iNOS mRNA进行RT-PCR并通过凝胶成像分析系统扫描RT-PCR产物,用内参半定量法分析iNOS mRNA的变化。结果对照组无iNOS mRNA表达,各染铀组扩增产物电泳条带吸光度值(A)明显高于对照组(P<0.05);其中13、mg组产物电泳条带A值逐渐增高,3 mg组到达高峰,5 mg组产物电泳条带A值明显低于13、mg组(P<0.05)。结论DU颗粒气管灌注能使大鼠肺组织iNOS mRNA表达水平升高,并与DU剂量呈正相关。DU剂量增高到一定程度则使iNOS mRNA表达水平降低,这种变化可能与DU化学毒性和辐射损伤的复合作用有关。     

Schneeberg lung disease and uranium mining in the saxon ore mountains (Erzgebirge)

The so-called Schneeberg lung disease is a form of bronchial or alveolar carcinoma caused by the effects of the radioactive gas radon and of its radioactive short half-life daughter products. This type of radiation-induced occupational cancer is the most common and the most important radiation injury among workers occupationally exposed to ionizing radiation. There have been many deaths from lung cancer, especially in the Soviet uranium mines in the Erzgebirge of Saxony in the former German Democratic Republic. The history of disease in these miners extends over five centuries; the first observations of their health hazard start in the Middle Ages. The discovery of the lung cancer component was made toward the end of the nineteenth century, and the suspicion that a connection might exist between this cancer type and exposure to ionizing radiation was voiced at the beginning of the twentieth century. In the first half of this century, further research was carried out on this disease in the Schneeberg area of the Erzgebirge. Before the end of World War II, guidelines were set up to define the acceptable limits of radon exposure in the ore mines of Saxony. After World War II, the American uranium mines in the Colorado Plateau used the German research results as a basis for working out their own radiation protection standard. The uranium mines under Soviet occupation in the former GDR, on the contrary, paid no attention to these research findings. For many years, no precautions were taken for the miners' working conditions. The consequence of this serious omission was an estimated 9,000 fatal cases of lung cancer among these underground miners. High concentrations of radon are to be found in indoor air of homes in some districts of the Erzgebirge, suggesting an increasing lung cancer risk for the local inhabitants. The significance of this finding is evaluated. © 1993 Wiley-Liss, Inc.     

浓缩铀诱发体细胞和生殖细胞的放射遗传毒理效应

为了解浓缩铀对人体的危害, 本文研究了浓缩铀诱发体细胞和生殖细胞的遗传毒理效应。结果表明:浓缩铀UO₂F_{2诱发体细胞的突变效应是:可导致骨漪细胞和外周血淋巴细胞的染色体畸变发生。同时细胞分裂指数亦受到明显抑制.而诱发生殖细胞的突变效应是:对精原细胞主要诱发染色体断片,而在初级精母细胞中观察到多价体发生,传递遗传损害.对雄性生殖细胞DNA损伤,观察到以受²³⁵U作用后12天的精子DNA洗脱率最高,对所致DNA链断裂程度之间呈现线性剂量效应关系.实验还观察到精子畸形,并随着精子发育阶段的不同而呈现不同程度的损伤效应.尤其在注入后的13天和36天阶段,精子畸形率呈显著增升.}     

二甲亚砜对染毒支气管上皮细胞的保护作用分析

目的在观察铀矿粉对体外培养的支气管上皮细胞的毒性作用同时,加入二甲亚砜,以了解其在支气管上皮细胞受铀矿粉染毒时的可能保护机制。方法将不同浓度的铀矿粉与体外培养的支气管上皮细胞进行长时间接触,分为对照组、染毒组和二甲亚砜（DMSO）保护组,通过血清抗性实验等,观察各组间细胞受损的情况。结果随着铀矿粉浓度的增高,支气管上皮细胞受损明显加重,加入二甲亚砜的支气管上皮细胞受损情况好于未加入者。DMSO对铀矿尘作用于BEAS-2B细胞后,可引起细胞DNA断裂,造成细胞拖尾率、彗星尾部DNA含量、尾长、尾部面积、尾距增加具有较好的抑制作用。结论铀矿粉对支气管上皮细胞有明显的恶性转化作用,可能是铀矿粉对肺损伤的主要机制,二甲亚砜具有一定的保护作用。     

含邻苯二酚基团的黄酮化合物促排急性贫铀中毒效果的研究

目的 寻找对急性贫铀中毒促排效果较好的含邻苯二酚基团的黄酮类化合物.方法 给予Wistar大鼠贫铀20 mg/kg,立即给予黄酮类化合物10 mg/kg,连续3 d,并设邻苯二酚类化合物8102及DMSO做为对照.3 d后做肾功能检测和肾脏、肝脏、骨髓、脾脏等病理观察.结果 8102和F1组血清肌酐和尿素氮含量显著下降,F2、T1和T2组的肌酐浓度也显著降低.病理观察显示,T2组肾脏、肝脏几乎无明显损伤;8102和T1次之;F1和QU 组肾损伤较重;DMSO组的损伤最重,但较贫铀组轻.结论 T2对贫铀敏感器官的保护最好;F1可改善肾功能.这两种化合物均具有做为贫铀促排剂的潜能.     

长期摄入低剂量贫铀对大鼠血象与肝肾功能的影响

目的研究长期摄入低剂量贫铀对大鼠的血象、肝肾功能的影响。方法给予初断乳大鼠含贫铀饲料,摄入贫铀的剂量分别为0、0.4、4、40mg·kg-1·d-1,随后的14个月内,临床生化自动检测仪测定外周血、肝肾功能的变化。结果F0代:小剂量组在14个月、中剂量组在10个月、高剂量组在7个月;F1代:中、高剂量组在10个月时出现白细胞显著降低,并由这些时相点开始出现各项血液学指标持续下降。随摄入贫铀剂量的增加,摄入时间的延长,白细胞和红细胞计数出现下降的时间越早,降幅越大;同一剂量组同一时相点,F1代比F0代降得更低。实验组肝功能与正常组没有显著差异(P>0.05)。肾功能指标仅有某个时相点血清肌酐上升,其余变化不显著(P>0.05)。结论长期摄入低剂量贫铀,只有在较长期或剂量较大时,可使外周血白细胞下降,继而红细胞、血小板计数下降;肾功能影响轻微,肝功能无影响。