Nordberg G F, Jin T, Hong F, Zhang A, Buchet J P, Bernard A
Environmental Medicine, Umeå University, S-901 87 Umeå, Sweden.
Toxicol Appl Pharmacol. 2005 Aug 7;206(2):191-7. doi: 10.1016/j.taap.2004.11.028.
Advances in proteomics have led to the identification of sensitive urinary biomarkers of renal dysfunction that are increasingly used in toxicology and epidemiology. Recent animal data show that combined exposure to inorganic arsenic (As) and cadmium (Cd) gives rise to more pronounced renal toxicity than exposure to each of the agents alone. In order to examine if similar interaction occurs in humans, renal dysfunction was studied in population groups (619 persons in total) residing in two metal contaminated areas in China: mainly a Cd contaminated area in Zhejiang province (Z-area) and mainly a As contaminated area in Guizhou province (G-area). Nearby control areas without excessive metal exposure were also included. Measurements of urinary beta(2)-microglobulin (UB2MG), N-acetyl-beta-glucosaminidase (UNAG), retinol binding protein (URBP) and albumin (UALB) were used as markers of renal dysfunction. Urinary Cd (UCd) and total As (UTAs) were analyzed by graphite-furnace atomic absorption spectrometry. Urinary inorganic As and its mono- and di-methylated metabolites (UIAs) were determined by Hydride generation. Results. As expected, the highest UCd values occurred in Z-area (Geometric mean, GM 11.6 microg/g crea) while the highest UTAs values occurred in G-area (GM = 288 microg/g crea). Statistically significant increases compared to the respective control area were present both for UTAs, UCd and for UB2MG, UNAG and UALB in Z-area as well as in G-area. UIAs was determined only in Z area. In G-area, there was a clear dose-response pattern both in relation to UTAs and UCd for each of the biomarkers of renal dysfunction. An interaction effect between As and Cd was demonstrated at higher levels of a combined exposure to As and Cd enhancing the effect on the kidney. In Z-area an increased prevalence of B2MG-uria, NAG-uria and ALB-uria was found in relation to UCd, but no relationship to UTAs was found. A statistically significant relationship between UIAs and UB2MG was found among women in this area and an interaction between As and Cd was indicated for B2MG. Conclusion. The present studies, which employed sensitive biomarkers of renal dysfunction, give support to the idea that human co-exposure to Cd and inorganic arsenic gives rise to more pronounced renal damage than exposure to each of the elements alone, but further studies are needed to establish and clarify this interaction.
蛋白质组学的进展已促使人们识别出肾功能障碍的敏感尿液生物标志物，这些标志物在毒理学和流行病学中越来越常用。最近的动物数据表明，与单独接触无机砷（As）和镉（Cd）中的任何一种相比，同时接触这两种物质会导致更明显的肾毒性。为了研究人类是否也会出现类似的相互作用，我们对居住在中国两个金属污染地区的人群（共619人）的肾功能进行了研究：主要是浙江省的一个镉污染地区（Z地区）和贵州省的一个砷污染地区（G地区）。还纳入了附近没有过度金属暴露的对照地区。测量尿β2微球蛋白（UB2MG）、N - 乙酰 - β - 氨基葡萄糖苷酶（UNAG）、视黄醇结合蛋白（URBP）和白蛋白（UALB）作为肾功能障碍的标志物。尿镉（UCd）和总砷（UTAs）通过石墨炉原子吸收光谱法进行分析。尿无机砷及其单甲基和二甲基代谢物（UIAs）通过氢化物发生法测定。结果。正如预期的那样，Z地区的UCd值最高（几何均值，GM = 11.6 μg/g肌酐），而G地区的UTAs值最高（GM = 288 μg/g肌酐）。与各自的对照地区相比，Z地区和G地区的UTAs、UCd以及UB2MG、UNAG和UALB均有统计学显著升高。仅在Z地区测定了UIAs。在G地区，对于每种肾功能障碍生物标志物，UTAs和UCd均呈现明显的剂量反应模式。在较高水平的砷和镉联合暴露时，砷和镉之间存在相互作用效应，增强了对肾脏的影响。在Z地区，与UCd相关的B2MG尿、NAG尿和ALB尿患病率增加，但未发现与UTAs有关。在该地区女性中发现UIAs与UB2MG之间存在统计学显著关系，并且表明砷和镉在B2MG方面存在相互作用。结论。本研究采用了肾功能障碍的敏感生物标志物支持了这样一种观点，即人类同时接触镉和无机砷比单独接触每种元素会导致更明显的肾损伤，但需要进一步研究来确定和阐明这种相互作用。
