Global screening of human cord blood proteomes for biomarkers of toxic exposure and effect.

Global screening of human cord blood proteomes for biomarkers of toxic exposure and effect.
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DOI:
10.1289/ehp.11816
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发表时间:
2009-05
影响因子:
10.4
通讯作者:
Halden RU
Halden RU
中科院分区:
环境科学与生态学1区
文献类型:
--
作者:
Colquhoun DR;Goldman LR;Cole RN;Gucek M;Mansharamani M;Witter FR;Apelberg BJ;Halden RU

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孕妇接触天然和人造化学品会对婴儿的健康造成负面影响,从出生体重过低到发育缺陷。在某些情况下,假定疾病的基础是在子宫内或幼儿期接触有毒物质。因此,了解胎儿对环境暴露的反应是至关重要的。为此,脐带血是一种容易获得的生物流体,与成人相比,其蛋白质组学组成大部分尚未被探索。我们的目标是对胎儿血清蛋白质组进行初步的全球评估,并鉴定与母体吸烟有关的子宫内毒性暴露的蛋白质生物标志物。从300个样本库中,我们选择了6名吸烟者和6名非吸烟者所生的12名婴儿的脐带血血清,并通过串联质谱法结合等压标签(iTRAQ)进行蛋白质定量分析。我们鉴定了203种蛋白质,其中17种在香烟烟雾暴露人群和对照人群中表达差异。大多数确定的候选生物标志物在生物学上是合理的,因此强调了用全球蛋白质组学技术筛选新生儿暴露生物标志物和子宫内化学物质暴露引发的早期生物学效应的可行性。这项验证性研究提供了人类脐带血血清蛋白质组的初步观点;它证明了利用蛋白质组学,环境,有毒暴露的生物标志物识别其中的可行性。
Exposures of pregnant women to natural and manmade chemicals can lead to negative health effects in the baby, ranging from low birth weight to developmental defects. In some cases, diseases were postulated to have their basis in toxic exposure in utero or in early childhood. Therefore, an understanding of fetal responses to environmental exposures is essential. To that end, cord blood is a readily accessible biofluid whose proteomic makeup remains mostly unexplored when compared with that of adults. Our goal was an initial global assessment of the fetal serum proteome and for the identification of protein biomarkers indicative of toxic in utero exposures related to maternal cigarette smoking. Drawing from a repository of 300 samples, we selected umbilical cord blood sera from 12 babies born to six smokers and six nonsmokers and analyzed both sample pools by tandem mass spectrometry in conjunction with isobaric tags (iTRAQ) for protein quantification. We identified 203 proteins, 17 of which were differentially expressed between the cigarette smoke–exposed and control populations. Most of the identified candidate biomarkers were biologically plausible, thereby underscoring the feasibility of screening neonates with global proteomic techniques for biomarkers of exposure and early biological effects triggered by in utero chemical exposures. This validation study provides an initial view of the proteome of human cord blood sera; it demonstrates the feasibility of identifying therein by use of proteomics, biomarkers of environmental, toxic exposures.
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