Institute of Occupational Medicine and Industrial Hygiene, College of Public Health , National Taiwan University , No. 17, Xu-Zhou Road , Taipei 10055 , Taiwan.
The Metabolomics Core Laboratory, Center of Genomic Medicine , National Taiwan University , No. 1, Sec. 4, Roosevelt Road , Taipei 10617 , Taiwan.
Environ Sci Technol. 2019 May 7;53(9):5454-5465. doi: 10.1021/acs.est.9b00392. Epub 2019 Apr 24.
Studies on metabolomes of carcinogenic pollutants among children and adolescents are limited. We aim to identify metabolic perturbations in 107 children and adolescents (aged 9-15) exposed to multiple carcinogens in a polluted area surrounding the largest petrochemical complex in Taiwan. We measured urinary concentrations of eight carcinogen exposure biomarkers (heavy metals and polycyclic aromatic hydrocarbons (PAHs) represented by 1-hydroxypyrene), and urinary oxidative stress biomarkers and serum acylcarnitines as biomarkers of early health effects. Serum metabolomics was analyzed using a liquid chromatography mass spectrometry-based method. Pathway analysis and "meet-in-the-middle" approach were applied to identify potential metabolites and biological mechanisms linking carcinogens exposure with early health effects. We found 10 potential metabolites possibly linking increased exposure to IARC group 1 carcinogens (As, Cd, Cr, Ni) and group 2 carcinogens (V, Hg, PAHs) with elevated oxidative stress and deregulated serum acylcarnitines, including inosine monophosphate and adenosine monophosphate (purine metabolism), malic acid and oxoglutaric acid (citrate cycle), carnitine (fatty acid metabolism), and pyroglutamic acid (glutathione metabolism). Purine metabolism was identified as the possible mechanism affected by children and adolescents' exposure to carcinogens. These findings contribute to understanding the health effects of childhood and adolescence exposure to multiple industrial carcinogens during critical periods of development.
儿童和青少年中致癌污染物代谢组学的研究有限。我们旨在识别暴露于台湾最大石化综合体周围污染地区的 107 名 9-15 岁儿童和青少年中代谢物的变化。我们测量了八种致癌暴露生物标志物（重金属和多环芳烃（以 1-羟基芘表示））以及尿液氧化应激生物标志物和血清酰基辅酶 A 作为早期健康影响的生物标志物。使用基于液相色谱质谱的方法对血清代谢组学进行分析。采用途径分析和“中间相遇”方法来确定潜在的代谢物和将致癌剂暴露与早期健康影响联系起来的生物学机制。我们发现了 10 种潜在的代谢物，它们可能与 IARC 第 1 组（As、Cd、Cr、Ni）和第 2 组（V、Hg、PAHs）致癌剂的暴露与氧化应激增加和血清酰基辅酶 A 失调有关，包括肌苷单磷酸和腺苷单磷酸（嘌呤代谢）、苹果酸和草酰乙酸（柠檬酸循环）、肉碱（脂肪酸代谢）和焦谷氨酸（谷胱甘肽代谢）。嘌呤代谢被确定为儿童和青少年暴露于致癌剂影响的可能机制。这些发现有助于理解儿童和青少年在发育关键期暴露于多种工业致癌剂的健康影响。
