Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population.
Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population.
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DOI：
10.1186/1741-7015-10-61
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发表时间：
2012-06-19
期刊：
影响因子：
9.3
通讯作者：
Keun HC
中科院分区：
文献类型：
--
作者：
Ellis JK;Athersuch TJ;Thomas LD;Teichert F;Pérez-Trujillo M;Svendsen C;Spurgeon DJ;Singh R;Järup L;Bundy JG;Keun HC
“暴露组”代表一生中所有环境暴露的累积。需要自上而下的策略来评估如此全面的事物，并且可以改变我们对环境因素如何影响人类健康的理解。代谢分析（代谢组学/代谢组学）定义了个体的代谢表型，该表型受基因型、饮食、生活方式、健康和外源性物质暴露的影响，还可以揭示疾病风险的中间生物标志物，反映对暴露的适应性反应。我们调查了生活在环境污染点源附近的志愿者的新陈代谢变化：一个封闭的锌冶炼厂，环境镉含量升高。使用高分辨率 1H NMR 波谱（代谢组学）获取 178 名人类志愿者的尿液代谢谱。对光谱数据进行多变量和单变量分析，以确定与生活方式或生物因素相关的代谢物。还使用质谱法测量了 8-氧代-脱氧鸟苷的尿液水平，作为全身氧化应激的标志。六种尿液代谢物与线粒体代谢（柠檬酸盐、3-羟基异戊酸、4-脱氧赤藓酸）或一碳代谢（二甲基甘氨酸、肌酸酐、肌酸）相关，与镉暴露相关。特别是，在控制年龄和性别后，柠檬酸盐水平与尿镉和吸烟状况保持显着相关。在镉暴露量高的个体中，氧化应激（根据尿 8-氧代脱氧鸟苷水平测定）升高，这支持了重金属积累导致线粒体功能障碍的假设。这项研究表明，在不受控制的人群中进行基于核磁共振的代谢分析研究能够识别真实环境浓度下有毒物质反应的中间生物标志物，为暴露组研究铺平道路。
The 'exposome' represents the accumulation of all environmental exposures across a lifetime. Top-down strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics) defines an individual's metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium. High-resolution 1H NMR spectroscopy (metabonomics) was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress. Six urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4-deoxy-erythronic acid) or one-carbon metabolism (dimethylglycine, creatinine, creatine), were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels) was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction. This study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental concentrations, paving the way for exposome research.
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影响因子：
10.4
作者：
Benbrahim-Tallaa L;Waterland RA;Dill AL;Webber MM;Waalkes MP
通讯作者：
Waalkes MP
影响因子：
13.2
作者：
Hellström, L;Elinder, CG;Axelson, O
通讯作者：
Axelson, O
影响因子：
3.5
作者：
Griffin, JL;Walker, LA;Nicholson, JK
通讯作者：
Nicholson, JK
影响因子：
4.9
作者：
Chalkley, SR;Richmond, J;Barltrop, D
通讯作者：
Barltrop, D
DOI：
10.1081/clt-120021102
发表时间：
2003-01-01
期刊：
JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY
影响因子：
--
作者：
Cardellach, F;Alonso, JR;Miró, O
通讯作者：
Miró, O