Analyses of chromium and nickel in human pulmonary tissue

Summary After inhalative occupational exposure to certain compounds containing nickel and chromium (mostly over many years), an accumulation of these metals may occur in the lung tissue. This is of particular importance, both from a toxicological point of view and with regard to expert reports, since certain nickel and chromium compounds may induce lung cancers. In the context of this study, samples of pulmonary tissue from 34 deceased persons from the Bergen area (Norway) were analysed by atomic absorption spectrometry with regard to their content of chromium and nickel. The deceased comprised 21 men and 13 women. In 15 cases, death resulted from lung cancer; in the other 19 deceased, there was no indication of a malignant disease of the airways. The concentrations of nickel found in the lung tissue do not differ between patients with lung cancer and patients with healthy lungs. On the other hand, the concentration of chromium in the pulmonary tissue in the patients who had died of lung cancer and who had all been inhalative smokers, are higher (statistically significant) than in the nonsmokers or in those with healthy lungs. An accumulation of these two metals in the tumor matrix could not be detected. Both the average nickel and the average chromium concentrations were higher in the persons who had probably been exposed occupationally. Considering the present state of scientific knowledge, the aspects relevant to expert reports which result from the analyses of metals in the pulmonary tissue are discussed.     

Biomonitoring of nickel and chromium in human pulmonary tissue

Nickel (Ni) and chromium (Cr) and some of its compounds may be able to induce cancer in the lungs as well as in the nose and paranasal sinuses after occupational exposure. Latency periods amount to 20 years and more. Therefore objective exposure data are not available in the most cases and expert evaluation of the causal connection is often difficult. Recent investigations have shown, that Ni and Cr can cumulate in human lung tissue after occupational exposure. For the evaluation of normal Ni- and Cr-values a total of 495 human lung tissue samples of 30 occupationally non-exposed persons were analysed by AAS including ZEEMAN-compensation after wet oxidative digestion. Additional samples of 10 deceased persons who have been occupationally exposed to nickel in previous times by nickel-refining and welding, especially flame spraying have been investigated. The median Ni- and Cr- concentrations in the lungs of the non-exposed persons ranged between 20–40 resp. 133–277 ng/g (wet weight). In nickel refinery workers Ni- concentrations were found which exceeded the normal range about 1,000. In welders, especially flame sprayers, also values more than 100 times higher could be analysed for Ni and Cr. Partially these concentrations were found years after the end of the inhalative exposure.     

Problems in establishing norm values for nickel and chromium concentrations in human pulmonary tissue

In 15 random autopsies, nickel (Ni) and chromium (Cr) were determined quantitatively by atomic absorption spectrometry (AAS) in human lung tissue to evaluate norm values. None of the deceased persons had had an occupational exposure to Cr or Ni or their compounds. In all, 22 tissue samples were taken from each lung at specific topographical anatomical locations. The analytical procedure is described in detail. The results showed substantial variation in concentrations both within a single lung and also between individuals. Median values found were 204 ng/g for Cr and 25.6 ng/g for Ni. Topographical concentrations of Cr and Ni were 1.3-1.9 times higher in the upper lung areas. In view of the variability in metal concentration, analysis of only one part of lung tissue is not sufficient for determining the content of the entire lung. The evaluation of norm values is an important precondition for appraisal of Cr and Ni accumulation in human pulmonary tissue that may be due to occupational exposure.     

Investigations on the quantitative determination of nickel and chromium in human lung tissue

Summary Nickel (Ni) and some of its relatively insoluble compounds as well as chromates may be able to induce cancer in the region of the lungs, as well as in the nose and paranasal sinuses after occupational exposure. Latency periods may amount to 20 years and more. The results of recent investigations have shown that these metals cumulate in the lung tissue after inhalation of relatively insoluble chromium and nickel compounds. The quantitative detection of these heavy metals in samples of pulmonary tissue hence permits the amount of past exposure to be estimated. To establish the normal values, samples of pulmonary tissue from 30 normal subjects were investigated for chromium and nickel content. The samples were taken from different segments and lobes of the lungs, taking topographical anatomical criteria into consideration. In addition, 15 persons who had formerly been exposed to nickel and/or chromium (11 nickel refinery workers, of whom 10 had died of lung cancer, 2 stainless steel welders, 1 foundry worker, 1 electrical technician) were also investigated. From the results of 495 tissue samples from the normal group, median chromium concentrations between 130 and 280 ng/g were calculated, with median nickel concentrations of 20–40 ng/g (wet weight). If these values are related to the nickel concentrations measured in refinery workers, values 112-5,860 times higher were found. The concentrations were about 500 times higher than normal for nickel, and about 60 times higher than normal for chromium in the stainless steel welders. For the foundry workers who died of lung cancer, chromium and nickel concentrations in the normal range were calculated, with the exception of the nickel concentrations in the upper and lower lobes of the right lung. The very high nickel concentrations found in the samples of lung tissue from former nickel refinery workers should be regarded as a guideline with regard to the appraisal of the causal relationship between lung cancer and occupational exposure to relatively insoluble nickel compounds. This result is also supported by epidemiological investigations on this subgroup and must thus be considered etiologically conclusive. For the welders, chromium and nickel concentrations were found that were markedly above normal, but as yet there is no epidemiologically reliable verification for the increased occurrence of malignancies in this occupational group. On the basis of present scientific knowledge, no indications were found of relevant chromium and/or nickel exposure of the lung tissue that might be able to induce lung cancer in either foundry workers or for electric technicians.Dedicated to Professor V. Becker on his 65th birthday     

Chromium in exhaled breath condensate and pulmonary tissue of non-small cell lung cancer patients

Objective Chromium in exhaled breath condensate (EBC) has recently been proposed as a biomarker of pulmonary exposure. The aim of this study was to measure the Cr levels in the EBC and pulmonary tissue of patients with early, operable non-small cell lung cancer (NSCLC) who had not been occupationally exposed to Cr before and after tumour resection and to correlate Cr in lung tissue with that in EBC. Methods Cr levels in the EBC and pulmonary tissue of 20 NSCLC patients were measured by means of electrothermal atomic absorption before and after tumour resection. Cr levels were also measured in the urine of 15 of these patients. Results The pre-surgery EBC Cr levels of the NSCLC patients were not different from those of the controls, but both EBC and urinary Cr levels increased after surgery. There was a significant correlation between Cr levels in EBC and pulmonary tissue (R = 0.55, P = 0.01), but not between these and urinary Cr levels. Conclusion Cr levels in EBC and urine of NSCLC patients were increased after surgical intervention. Measured Cr EBC levels were by one order of magnitude lower than those observed in moderately exposed workers. This fact, together with the correlation between Cr in EBC and in pulmonary tissue, confirms that EBC is a promising biological fluid to test pulmonary exposure to Cr, giving complementary information to that provided by urinary Cr, not correlated with EBC and tissue.     

Distribution of nickel in lungs from former nickel workers

Objective: The purpose of this work was to study the distribution of nickel within lung tissue obtained from nickel-exposed people and to evaluate the␣use of only one single sample for determination of the nickel burden of the lung. Methods and materials: The material used was lung tissue obtained from 15 former nickel refinery workers who had been exposed to a variety of nickel compounds such as Ni₃S₂, NiO, Ni⁰, NiSO₄, and NiCl₂. Ten samples taken from different locations of the lung as well as from the right and left bronchus and from the right lower lobe (total 13 samples per individual) were analyzed for nickel by electrothermal atomic absorption spectrometry. Samples obtained from ten people not connected to the refinery served as a reference group. Results: The arithmetic mean value ± SD for nickel concentration was 50 ± 150 μg g⁻¹ dry wt. Biopsies collected on the center of the lower right lobe had an average nickel concentration of 82 ± 252 μg g⁻¹. The average nickel concentration detected in the right and left bronchus was 5.9 ± 11.6 and 3.8 ± 6.0 μg g⁻¹, respectively. Lung tissue obtained from ten people not connected to the refinery had an average nickel concentration of 0.74 ± 0.44 μg g⁻¹. Conclusions: The significant findings based on log-normal distribution of the nickel concentration were as follows: (1) samples obtained from the right lung showed no significant difference from samples taken from the left lung–a comparison of the nickel concentration detected in all the lung lobes showed that no single lobe differed from another; (2) the concentration of nickel found in the main bronchus of the refinery workers, although elevated, was significantly lower than the concentration detected in the remaining tissue; and (3) one single biopsy did not reflect the nickel burden of the lung. Received: 20 November 1997 / Accepted: 21 April 1998     

Cadmium in human lung tissue

Summary In 101 unselected autopsies, cadmium (Cd) in lung tissue was analyzed by means of flameless atomic absorption spectrometry (AAS). The subjects originated from Bochum (BO), Dortmund (DO), and neighbouring cities in the Ruhr District (BO/DO) as well as from Muenster (MS) and vicinity. The sample included eight persons who had died from bronchial carcinoma. The Cd concentration in lung tissue (CdL) did not show a significant age-dependency. There was only a slight increase of CdL in the age around 50. For males, the median CdL value was found to be 1.32 g/g dry wt in the age group from 20–45, 1.48 g/g dry wt from 45–65, and 0.64 g/g dry wt > 65 (the corresponding means and standard deviations were 1.48 ± 1.22, 1.73 ± 1.42, and 1.18 ± 1.27 g/g dry wt). CdL in men was twice that in women. There were no differences between the two regions (BO/DO : MS) examined. CdL of the bronchial carcinoma cases were mostly clearly above the expected level, often similar to the Cr and Ni concentration of the same specimens. Besides the amount of inhaled metal aerosols, insufficient lung clearance may play a leading role for their retention in lung parenchyma. However, with regard to the determination of causality between uptake and disease the data are difficult to interpret, in our study due to a lack of enough consistent and reliable data on occupation, environment, and smoking habits, and in general due to a lot of variables which, until now, cannot be sufficiently quantified.     

镍、铬等金属与非职业暴露人群肺癌的关系

目的　研究镍、铬等金属毒物在非职业暴露人群肺癌发生中的作用。方法　收集无金属类毒物职业接触史、经手术切除的肺癌组织 5 5例 ,肺良性病变或意外死亡者的正常肺组织 2 3例 ,用感耦等离子体 -原子发射光谱仪 (ICP -AES)检测肺组织中镉 (Cd)、铬 (Cr)、镍 (Ni)、铅 (Pb)、铍 (Be)、砷 (As)等金属和类金属毒物的含量 ,按吸烟史和细胞类型进行分层分析 ;并用硫化镍和苯并 (a)芘 -C ,8,二醇 - 90环氧化物 (BPDE)诱导正常人气管上皮细胞系发生恶性转化的癌变模型 ,检测转化细胞经裸鼠成瘤组织的金属类毒物的含量。结果　在肺组织中可检出多种金属类毒物 ,在肺癌组织中镍和铬的含量分别为 ( 10 5 172± 2 6 73 9)和 ( 7 6 90 6± 3 10 12 ) μg/ g干肺组织 ,显著高于正常肺组织的镍、铬含量 ( 4 12 18± 2 175 2 )和 ( 4 12 44± 2 75 38) μg/g干肺组织 ,t值分别为 10 14和 5 0 4,P <0 0 1。按吸烟和细胞类型分层 ,吸烟者肺组织中的镍、铬含量皆高于非吸烟者 ,P <0 0 5 ;肺鳞癌中镍的含量 ( 12 5 6 0 9± 2 345 5 )μg/ g干肺组织高于肺腺癌 ( 8 2 377± 2 782 8) μg/ g干肺组织 ,t=6 2 5 ,P <0 0 1。在用硫化镍和BPDE诱导正常人气管上皮细胞系发生恶性转化经裸鼠成瘤的癌组织中 ,硫化镍诱     

Inorganic fibres in the lung tissue of Hungarian and German lung cancer patients

Objective: To ascertain the lung burden of asbestos fibres in Hungarian lung cancer patients in comparison with the cumulative asbestos exposure estimated from the occupational history. Methods: For 25 Hungarian lung cancer patients, lung tissue fibre analysis was performed by scanning transmission electron microscopy (STEM) and counting of ferruginous bodies (FBs) by light microscopy. Cumulative asbestos exposure in fibre-years was assessed from a standardised occupational history using the report “fibre years” of the German Berufsgenossenschaften. Results: Median and maximum concentrations of fibres longer 5 μm per gram dry lung tissue (g dry) were 0.03 and 7.38 million fibres/g dry for chrysotile, 0.00 and 0.21 million fibres/g dry for amphibole and 0.22 and 0.62 million fibres/g dry for other mineral fibres (OMFs). The maximum values were observed in one patient for whom a high asbestos exposure was evident in advance from the occupational history. Conclusions: In comparison with reference values obtained by the same method for German patients with no indication of workplace asbestos exposure, increased concentrations of more than 0.2 million chrysotile fibres/g dry were obtained for six of the 25 Hungarian patients (24%). For one of them, the second highest estimate of a workplace exposure of 60 fibre-years and the highest tissue concentration of 7.38 million chrysotile fibres/g dry substantiate a high probability of a causal relationship to asbestos. A further comparison can be made with the results for 66 German patients treated by surgical lung resection for a disorder other than mesothelioma, mainly lung cancer. For the Hungarian lung cancer patients, similar amounts of chrysotile but distinctly lower amounts of amphibole fibres and distinctly higher amounts of OMFs were observed. A correlation between exposure estimates from occupational history and concentration of fibres in the lung tissue was observed for amphibole (Spearman: R=0.66, P < 0.001, Pearson: R=0.50, P=0.01) and for chrysotile (Pearson: R=0.48, P=0.02). Received: 3 May 2000 / Accepted: 14 September 2000     

人肺组织DNA加合物含量的某些影响因素分析

为探讨人肺组织ＤＮＡ加合物的形成与某些影响因素之间的关系，分析了３７例肺癌患者（男１９例、女１８例）及３７例非肺癌肺部疾病患者（男１９例、女１８例）肺组织ＤＮＡ加合物的含量与年龄、性别、吸烟等影响因素之间的关系。结果表明：引起肺组织ＤＮＡ加合物含量增高的主要因素是吸烟；年龄、性别与肺组织ＤＮＡ加合物含量无相关性。     

原发支气管肺癌合并贫血的临床分析

目的 探讨原发支气管肺癌合并贫血的原因、特征及治疗。方法 回顾近十余年内我院334例肺癌住院患者的资料。结果 确诊支气管肺癌并发贫血76例，轻度34例，中度37例，重度5例。68例行骨髓穿刺涂片检查，确诊骨髓转移35例。7例患者用促红细胞生成素(EPO)治疗，近期有效。结论 肺癌并贫血约占22．8％，多为轻至中度。最常见的原因为骨髓转移，与营养不良、显性或不显性失血等因素也有关。EPO减少是否为重要原因，待进一步探讨。     

人肺癌和癌旁正常组织中稀土元素含量及分布

分析稀土元素 (REE)在肺癌及癌旁正常组织中的分布情况 ,比较肺癌患者与正常人肺组织中REE的含量及分布 ,为进一步研究REE与肿瘤的关系提供线索。用电感耦合等离子质谱仪 (ICP MS)方法测定了10例肺癌病人的癌及癌旁正常组织中 15种REE的含量 ,并与在同一实验室中用相同仪器条件测定的 13例正常人肺组织中REE的含量和分布进行了比较。样品在北京大学公共卫生学院中心仪器室测定 ,用光谱纯的铼 (Re)作为内标元素补偿 ,仪器可以自动校正氧化物的干扰。 15种REE的加标回收率在 92 9%～111 3%之间 ,变异系数在 0 96～ 3 0 7之间 ,方法的检出限为 0 0 0 5～ 0 0 2 5ng g。结果发现 :癌旁正常组织中15种REE的含量为癌组织中的 2 0 7～ 2 5 1倍 ;正常人肺组织中 ,除Ce外其他REE含量均低于癌旁正常组织 ,La、Pr、Nd的含量略高于肺癌组织 ,其他元素则低于肺癌组织。肺癌及癌旁正常组织REE的分布曲线基本一致 ,均有Ce的正异常 (δCe分别为 1 15 2和 1 2 37)和Eu的负异常 ((δEu分别为 0 5 72和 0 6 0 2 )。正常人肺组织REE的分布曲线Ce的正异常和Eu的负异常更明显 ,δCe=2 798,δEu=0 2 78。结果还显示正常人肺组织中轻稀土元素的配分显著高于肺癌和癌旁正常组织 ,中和重稀土配分则显著低于肺癌及癌旁正?     

不同玻璃液冻存人卵巢组织的近期异种移植效果的比较

目的:通过研究不同的玻璃液对人卵巢组织冻存后的近期异种移植效果,以筛选出较优的玻璃化冷冻方案。方法:收集2018年3月至2019年12月期间在北京大学深圳医院因妇科疾病行手术治疗的4例患者卵巢组织,将卵巢组织分割成5~10 mm×10 mm×1 mm的小块,分为新鲜对照组和4个处理组,4个处理组分别放入G1、G2、G3...     

低剂量铬暴露工人铬鼻病调查分析

六价铬 [hexavalent chromium,Cr（VI）] 是通过将矿物中的三价铬在有氧条件下加热得到 ,其广泛应用在工业生产中,研究表明,Cr（VI）可诱导机体氧化应激、DNA损伤和染色体不稳定,产生细胞毒性并造成遗传损伤,增加肺癌、鼻咽癌、肝和肾的毒性损伤、心脏功能障碍、过敏性接触性皮炎或铬溃疡等相关疾病的风险,长期职业接触Cr（VI）可导致肺癌的发生。近年,六价铬化合物先后被列入我国《优先控制化学品名录（第一批）》和《有毒有害水污染物名录（第一批）》的危险化学物质。本文就近年的相关文献报道,从Cr（VI）的细胞毒性、Cr（VI）暴露的动物和接触Cr（VI）的人群3个方面概述Cr（VI）诱发肺癌的潜在分子机制,为后续的相关研究提供参考。     

成纤维细胞特异蛋白-1在肺癌中的表达及其临床生物学意义

目的研究成纤维细胞特异蛋白-1(S100A4)在人肺癌中的表达及其临床生物学意义,探讨其在肺癌侵袭和转移中的作用。方法采用S-P免疫组化法检测50例肺癌及6例正常肺组织中S100A4的表达水平。结果S100A4在肺癌中表达显著高于正常肺组织;非小细胞肺癌中表达明显高于小细胞肺癌(P<0.05);腺癌中表达明显高于鳞癌(P<0.05)。S100A4表达与非小细胞肺癌临床病理特征关系密切,在有淋巴结转移组与无转移组中两者均差异有统计学意义(P<0.05)。在肺癌不同临床TNM分期中,S100A4阳性表达随临床分期的升高而明显增加,各期间均差异有统计学意义(P<0.05)。S100A4阳性率随肺癌细胞分化程度的降低也有升高趋势,但差异无统计学意义。S100A4表达与肿瘤大小有密切的正相关关系,随肿瘤体积的增大,S100A4的阳性率升高(P<0.05)。结论S100A4与肺癌的侵袭和转移有密切的关系,可以作为评估肺癌病人预后的重要指标。     

Age, sex, and region adjusted concentrations of chromium and nickel in lung tissue

Chromium (Cr) and nickel (Ni) concentrations were measured in lung tissue from 110 random necropsies by means of atomic absorption spectrometry. The subjects originated from the Ruhr district (Bochum (71 cases) and Dortmund (16 cases) areas), which has been defined as a particular pollution area with locally high Cr and Ni emissions, and from Münster and vicinity (23 cases). The Cr and Ni concentrations in lung tissue of the subjects from the Ruhr district (3.09 (SD 2.99) micrograms Cr/g, 0.65 (SD 0.94) micrograms Ni/g dry weight of lung) were 4.8 and 2.8 times higher than those from Münster (0.66 (SD 0.49) micrograms Cr/g, 0.17 (SD 0.11) micrograms Ni/g dry weight of lung). Concentrations of Cr and Ni in men were twice those in women. All data showed an age dependent increase of Cr and Ni in the lung (about 2.4% a year for Cr and 3% a year for Ni) and Cr and Ni values showed a high correlation (r greater than or equal to 0.9). Thus it was possible to calculate age, sex, and region adjusted expected values of pulmonary Cr and Ni concentrations, and to identify the difference between expected and observed values. This might be helpful to interpret measurements in individual cases and in epidemiological studies. With this procedure the six cases of bronchial carcinoma in the series were shown to have pulmonary Cr and Ni concentrations that were mostly well above the predicted values, and it was possible to give a rough estimate of the degree of deviation.     

Lung-retained contaminants,urinary chromium and nickel among stainless steel welders

Summary The magnetic method of measuring the amount of lung retained contaminants as well as urinary chromium and nickel determinations have been performed among 83 stainless steel (SS) welders who have used matural metal arc (MMA) and tungsten inert gas (TIG) welding techniques. The welders were divided into four groups according to the time percentage used for MMA welding. Only exposure to MMA/SS welding fumes resulted in clearly elevated chromium concentrations in the urine, the correlation coefficient between the values of urinary chromium and MMA/SS percentage being very significant (P < 0.001). Among the smokers the urinary chromium values were increased (P < 0.05) perhaps owing to contaminated cigarettes. In many workplaces the urinary chromium values of several welders exceeded the value of 30 g/l which is the recommended reference value in Finland. Owing to the solubility properties of nickel compounds in SS welding fumes urinary nickel concentrations were only slightly elevated among MMA/SS welders, and therefore, the urinary nickel determinations do not reflect the level of exposure to nickel compounds. The measured average remanent magnetic field of the chest area correlated well (P < 0.01) with the use of the MMA technique. A very significant correlation (P < 0.001) existed between the average remanent magnetic fields of the chest and the urinary chromium values of MMA/SS welders.