血铀浓度与肾损伤的关联性研究

目的研究人群血铀浓度与肾损伤间的关联。方法在湖南省4个铀矿分布地区开展病例对照研究, 分别纳入102例肾损伤病例和102例对照为病例组和对照组。使用条件logistic回归模型分析血铀浓度与肾损伤间的关联, 用限制性立方样条回归分析二者间的剂量反应关系。采用线性回归模型及Spearman相关来分析血铀浓度与肾损伤指标间的关联。结果全体研究对象血铀的中位浓度为8.94 ng/L, 病例组为10.19 ng/L。分析结果表明, 血铀可能是肾损伤的危险因素, 二者间存在剂量反应关系, 且呈非线性关联(χ2=5.15, P<0.05)。血铀浓度高暴露组发生肾损伤的危险性是低暴露组的4.21倍。血铀浓度与肾小球滤过率、血肌酐及β2微球蛋白等肾损伤指标关联密切(r=0.211、-0.142、0.195, P<0.05)。结论本研究表明血铀浓度与人群肾损伤之间存在统计学关联, 该结果可为肾损伤的预防提供流行病学依据。     

A normative value pilot study: levels of uranium in urine samples from UK civilians

A normative study of the levels of urinary uranium in the general UK population is needed for comparison with levels in UK military and ex-military personnel who served where munitions containing depleted uranium (DU) were used. As preparation, this pilot study trialled the process of collecting 24-h samples from adult male civilians, and compared the measurements from 24-h samples with those from spot samples taken over the subsequent 24h. The purpose was to assess the relative utility of the two types of samples. Twenty-five convalescent hospital in-patients were recruited as participants. Uranium concentrations in the 24-h samples ranged from 1 to 10.6 ng l(-1); in the spots, from not detectable to 38.1 ng l(-1). Normalised to creatinine, concentrations in the 24h samples ranged from approximately 100 to 800 ng mol(-1) creatinine; in the spot samples, from not detectable to approximately 4000 ng mol(-1) creatinine. The ranges appear similar to those reported for residents of the US. The distribution of spot sample results indicated that 95% of a participant's creatinine-adjusted concentrations from spot samples would be within the range 40-250% of his mean. Adjusting for creatinine almost entirely eliminated a slight indication of diurnal variation in urinary uranium concentration in spot samples. All the 24-h samples and 131 out of the 133 spot samples showed ratios of isotopes (238)U to (235)U consistent with natural uranium (i.e. neither enriched nor depleted). Slightly elevated ratios in two spot samples were not supported by other samples from the same participants, indicating that slightly elevated ratios may be recorded on very low concentration (<1 ng l(-1)) samples. In the main, quantification of this isotope ratio from spot samples was only slightly more variable than from 24-h samples. Complete 24-h urine samples gave better precision than spot samples in estimating uranium concentrations at these low levels, but presented more logistic difficulties in the collection of the samples. Clarification of the relative merits of alternative sampling strategies enables the design of a wider study to be optimised.     

Dose‐response relationships between internally‐deposited uranium and select health outcomes in gaseous diffusion plant workers, 1948‐2011

Objective

To examine dose‐response relationships between internal uranium exposures and select outcomes among a cohort of uranium enrichment workers.

Methods

Cox regression was conducted to examine associations between selected health outcomes and cumulative internal uranium with consideration for external ionizing radiation, work‐related medical X‐rays and contaminant radionuclides technetium (⁹⁹Tc) and plutonium (²³⁹Pu) as potential confounders.

Results

Elevated and monotonically increasing mortality risks were observed for kidney cancer, chronic renal diseases, and multiple myeloma, and the association with internal uranium absorbed organ dose was statistically significant for multiple myeloma. Adjustment for potential confounders had minimal impact on the risk estimates.

Conclusion

Kidney cancer, chronic renal disease, and multiple myeloma mortality risks were elevated with increasing internal uranium absorbed organ dose. The findings add to evidence of an association between internal exposure to uranium and cancer. Future investigation includes a study of cancer incidence in this cohort.

     

Effects of cell cycle phase on low-dose hyper-radiosensitivity

Purpose : To examine the low-dose radiation response of human glioma cell lines separated into different cell-cycle phases and to determine if low-dose hyper-radiosensitivity (HRS) differs in populations defined by cell-cycle position. To assess whether predictions of the outcome of multiple low-dose regimens should take account of cell-cycle effects. Materials and methods : The clonogenic survival of G1, G2 and S phase cells was measured after exposure to single doses of X-rays in two human glioma cell lines. One cell line (T98G) showed marked HRS when asynchronous cells were irradiated, while the other (U373) did not. Separation of populations and high-resolution cell counting was achieved using a fluorescence activated cell sorter. Sorted cell populations were irradiated with 240 kVp X-rays to doses between 0.05 and 5Gy. The resulting cell-survival versus dose data were comparatively fitted using the linear-quadratic and induced-repair models in order to assess the degree of HRS. Results : In both cell lines the low-dose response was altered when different populations were irradiated. In T98G cells, all populations showed HRS, but this was most marked in G2 phase cells. In U373 cells, no HRS was found in G1 or S phase cells, but HRS was demonstrable in G2 phase cells. Conclusions : HRS was expressed by the whole cell population of T98G cells but the size of the effect varied with cell-cycle phase and was most marked in the G2 population. In U373 cells, the effect could only be demonstrated in G2 cells. This implies that HRS is primarily a response of G2 phase cells and that this response dominates that seen in asynchronous populations. Actively proliferating cell populations may therefore demonstrate a greater increase in radiosensitivity to very low radiation doses compared with quiescent populations.     

The use of depleted uranium ammunition under contemporary international law: is there a need for a treaty-based ban on DU weapons?

This article examines whether the use of Depleted Uranium (DU) munitions can be considered illegal under current public international law. The analysis covers the law of arms control and focuses in particular on international humanitarian law. The article argues that DU ammunition cannot be addressed adequately under existing treaty based weapon bans, such as the Chemical Weapons Convention, due to the fact that DU does not meet the criteria required to trigger the applicability of those treaties. Furthermore, it is argued that continuing uncertainties regarding the effects of DU munitions impedes a reliable review of the legality of their use under various principles of international law, including the prohibition on employing indiscriminate weapons; the prohibition on weapons that are intended, or may be expected, to cause widespread, long-term and severe damage to the natural environment; and the prohibition on causing unnecessary suffering or superfluous injury. All of these principles require complete knowledge of the effects of the weapon in question. Nevertheless, the author argues that the same uncertainty places restrictions on the use of DU under the precautionary principle. The paper concludes with an examination of whether or not there is a need for – and if so whether there is a possibility of achieving – a Convention that comprehensively outlaws the use, transfer and stockpiling of DU weapons, as proposed by some non-governmental organisations (NGOs).     

Pulmonary toxicity after exposure to military-relevant heavy metal tungsten alloy particles

Significant controversy over the environmental and public health impact of depleted uranium use in the Gulf War and the war in the Balkans has prompted the investigation and use of other materials including heavy metal tungsten alloys (HMTAs) as nontoxic alternatives. Interest in the health effects of HMTAs has peaked since the recent discovery that rats intramuscularly implanted with pellets containing 91.1% tungsten/6% nickel/2.9% cobalt rapidly developed aggressive metastatic tumors at the implantation site. Very little is known, however, regarding the cellular and molecular mechanisms associated with the effects of inhalation exposure to HMTAs despite the recognized risk of this route of exposure to military personnel. In the current study military-relevant metal powder mixtures consisting of 92% tungsten/5% nickel/3% cobalt (WNiCo) and 92% tungsten/5% nickel/3% iron (WNiFe), pure metals, or vehicle (saline) were instilled intratracheally in rats. Pulmonary toxicity was assessed by cytologic analysis, lactate dehydrogenase activity, albumin content, and inflammatory cytokine levels in bronchoalveolar lavage fluid 24 h after instillation. The expression of 84 stress and toxicity-related genes was profiled in lung tissue and bronchoalveolar lavage cells using real-time quantitative PCR arrays, and in vitro assays were performed to measure the oxidative burst response and phagocytosis by lung macrophages. Results from this study determined that exposure to WNiCo and WNiFe induces pulmonary inflammation and altered expression of genes associated with oxidative and metabolic stress and toxicity. Inhalation exposure to both HMTAs likely causes lung injury by inducing macrophage activation, neutrophilia, and the generation of toxic oxygen radicals.     

盐酸氨溴索与柠檬酸廓清肺内难溶性贫铀的实验研究

目的：通过建立大鼠贫铀（ depleted uranium,DU）气溶胶气管灌注的实验模型,观察柠檬酸雾化吸入与盐酸氨溴索对肺内难溶性贫铀的廓清作用。方法雄性Wistar大鼠150只（体质量200±10 g）,随机分为正常对照组（ NC组）、贫铀气溶胶染毒组（ DU组）、DU＋雾化吸入柠檬酸组（ CA组）、DU＋盐酸氨溴索灌胃组（ AM组）、DU＋柠檬酸与盐酸氨溴索联用药组（ CA＋AM组）,分别在染毒后7、15、30 d活杀。微波消解法检测肺铀含量,观察肺组织病理改变,检测肺匀浆液炎性因子。结果与DU组相比,给药组在各时间点均明显减少肺内铀的沉积量（P＜0．01）,CA＋AM组肺铀含量低于单独用药组。肺组织病理HE染色显示,染毒后7、15、30 d,治疗组大鼠肺病变明显改善。肺匀浆液炎性因子检测显示,染毒后30 d,与DU组相比,治疗组IL-1α、IL-1β、IL-2水平降低,MCP-1、MIP-1α水平升高。结论使用柠檬酸和盐酸氨溴索均可明显提高肺铀廓清率,联合用药效果优于单独用药,且减轻难溶性铀颗粒对肺组织的破坏。药物治疗可以降低肺内炎性细胞因子水平,对肺部慢性炎症有抑制作用,并且增强巨噬细胞募集能力。     

某种材料防护贫铀粉尘效果的生物学评价

目的对一种材料防护贫铀(depleted uranium, DU)粉尘的效果进行生物学评价.方法吸入DU粉尘后第1、3天,收集无防护组和有防护组大鼠的血、肺、气管、肾和肝,测定铀含量,计算防护效果.结果有防护组各组织(体液)铀浓度均明显低于无防护组,防护效果在71.2%～96.1%之间.结论该种防护材料可阻挡绝大部分DU粉尘进入呼吸道,效果较好.     

水溶性印迹壳聚糖对贫铀致细胞毒性的解毒作用

利用印迹技术提高壳聚糖螯合铀的性能,探讨水溶性印迹壳聚糖是否能对贫铀(depleted uranium,DU)染毒细胞有解毒作用。首先筛选对铀酰离子(UO22+)螯合率高的印迹壳聚糖,再以人肾近端小管上皮细胞株(HK-2)DU(500μmol·L-1)染毒为模型,实验组加入壳聚糖(400 mg·L-1)和阳性对照组加入二乙烯三胺五乙酸(DTPA,50 mg·L-1)与DU共同作用下培养细胞。3个Cu2+印迹壳聚糖对DU螯合量超过49μg.mg-1,明显高于相应的非印迹壳聚糖;MTT测定DU污染组的细胞存活率为57.3%,加入Cu2+印迹戊二醛交联羧甲基壳聚糖Cu-P-CMC的实验组和DTPA螯合剂保护组的细胞存活率升高至88.7%和72.6%,细胞内DU蓄积量明显减少,细胞膜损伤和DNA损伤减轻,并且Cu-P-CMC解毒效果优于DTPA;透射电镜超微观察到,加入壳聚糖后的DU被壳聚糖螯合形成多个绒球,聚簇成串状或大团簇状,这种螯合物难进入细胞内而使细胞内DU蓄积量大大减少,因此缓解了DU对细胞的毒性。     

母血与脐血中铍钍铀的检测分析

目的了解铍、钍和铀3种有害微量元素在母体与胎儿体内的分布情况,为进一步研究它们对母、儿的毒性作用提供依据。方法选择125名住院分娩的产妇,取孕妇产前静脉血和分娩时胎儿脐静脉血,采用电感耦合等离子体-质谱(ICP-MS)法对全血样品进行铍、钍和铀质量浓度检测。结果母血中铍、钍和铀的检出率分别为55.2%、96.8%和64.0%,浓度分别为0.13、52.60和0.52μg/dl;胎儿脐血铍、钍和铀的检出率分别为55.2%、95.2%和70.4%,浓度分别为0.10、49.86和0.64μg/dl;3种有害元素浓度在母血与脐血间比较,差异均无显著性;相关分析表明,母血与脐血间铍、钍和铀的浓度呈显著正相关。结论母胎体内铍、钍和铀3种有害微量元素检出率较高,表明胎盘对胎儿没有发挥保护性屏障功能。