Urinary Metabolomics Revealed Arsenic Internal Dose-Related Metabolic Alterations: A Proof-of-Concept Study in a Chinese Male Cohort

被引：73

作者：

Zhang, Jie ^{[1
]}

Shen, Heqing ^{[1
]}

Xu, Weipan ^{[1
]}

Xia, Yankai ^{[2
]}

Barr, Dana Boyd ^{[3
]}

Mu, Xiaoli ^{[1
]}

Wang, Xiaoxue ^{[1
]}

Liu, Liangpo ^{[1
]}

Huang, Qingyu ^{[1
]}

Tian, Meiping ^{[1
]}

机构：

[1] Chinese Acad Sci, Key Lab Urban Environm & Hlth, Inst Urban Environm, Xiamen 350002, Fujian, Peoples R China

[2] Nanjing Med Univ, Inst Toxicol, Key Lab Reprod Med, Nanjing 210029, Jiangsu, Peoples R China

[3] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA

来源：

ENVIRONMENTAL SCIENCE & TECHNOLOGY | 2014年 / 48卷 / 20期

基金：

美国国家卫生研究院;

关键词：

INDUCED OXIDATIVE STRESS; ENDOCRINE DISRUPTOR; EXPOSURE; MELATONIN; TOXICOLOGY; CHEMICALS; ACID; RISK; CONTAMINATION; TESTOSTERONE;

D O I：

10.1021/es503659w

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

Urinary biomonitoring provides the most accurate arsenic exposure assessment; however, to improve the risk assessment, arsenic-related metabolic biomarkers are required to understand the internal processes that may be perturbed, which may, in turn, link the exposure to a specific health outcome. This study aimed to investigate arsenic-related urinary metabolome changes and identify dose-dependent metabolic biomarkers as a proof-of-concept of the information that could be obtained by combining metabolomics and targeted analyses. Urinary arsenic species such as inorganic arsenic, methylarsonic acid, dimethylarsinic acid and arsenobetaine were quantified using high performance liquid chromatography (HPLC)-inductively coupled plasma-mass spectrometry in a Chinese adult male cohort. Urinary metabolomics was conducted using HPLC-quadrupole time-of-flight mass spectrometry. Arsenic-related metabolic biomarkers were investigated by comparing the samples of the first and fifth quintiles of arsenic exposure classifications using a partial least-squares discriminant model. After the adjustments for age, body mass index, smoking, and alcohol consumption, five potential biomarkers related to arsenic exposure (i.e., testosterone, guanine, hippurate, acetyl-N-formyl-5-methoxykynurenamine, and serine) were identified from 61 candidate metabolites; these biomarkers suggested that endocrine disruption and oxidative stress were associated with urinary arsenic levels. Testosterone, guanine, and hippurate showed a high or moderate ability to discriminate the first and fifth quintiles of arsenic exposure with area-under-curve (AUC) values of 0.89, 0.87, and 0.83, respectively; their combination pattern showed an AUC value of 0.91 with a sensitivity of 88% and a specificity of 80%. Arsenic dose-dependent AUC value changes were also observed. This study demonstrated that metabolomics can be used to investigate arsenic-related biomarkers of metabolic changes; the dose-dependent trends of arsenic exposure to these biomarkers may translate into the potential use of metabolic biomarkers in arsenic risk assessment. Since this was a proof-of-concept study, more research is needed to confirm the relationships we observed between arsenic exposure and biochemical changes.

引用

页码：12265 / 12274

页数：10

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