Project 3: Discovery of Xenobiotics Associated with Preterm Birth

摘要 该项目的长期目标是发现导致早产的外源生物，依赖于 用质谱仪进行非靶向化学分析。这项研究的重点是波多黎各，因为 那里的早产发生率位居世界第二。将研究三种类型的样本： 尿液、胎盘和水。有五个具体目标。具体目标1涉及尿样，以及 研究波多黎各早产儿尿中含有不同的暴露组(外源或体内)的假说 环境化学物质暴露)，而不是足月尿。为了达到这个目的，大量的尿液(0.5加仑) 因为从每个孕妇身上收集的清晨空洞的堆积，然后是 用多孔萃取桨(搅拌装满2.0g颗粒吸附剂的“茶包”)提取。这 新技术产生了一种方便的储存库样本(袋子)，用于运输、储存和分析等分。 特定目标2涉及胎盘，因为它是假定的环境化学物质的目标组织， 可能会导致早产。这里的假设是波多黎各妇女(早产)的暴露 早产率17.7%)与波士顿的早产率(10.7%)在性质或数量上都不同。在这一特定情况下 目的，有机可提取的曝光组和形成dna加合物的曝光组都将在 胎盘。这一具体目标有助于应对波多黎各早产高发的可能性，因为 那里孕妇的曝光量普遍较高，早产和早产之间没有任何差异。 女人这个词。具体目标3侧重于胎盘细胞培养受到氧化应激和炎症的影响 (这可能是由外源生物引起的)，并试图了解这些应激培养中的DNA加合物是否 与波多黎各早产胎盘相似。具体目标4寻求识别地下的污染物 和波多黎各的自来水样本，以及相应的污染物降解产品 在项目5中，样品通过电解法进行修复。具体目标5建议提高灵敏度， 当前非靶向化学分析方法的范围和定性能力 通过离子标记结合衍生化。具体目标5的方法将用于关于 具体目标1、2和4。总体而言，该项目的潜力很大，有助于减少 早产；在建立和用质谱学表征来自于 正在从孕妇那里收集广泛的人口统计信息；在推动 一般情况下，非定向化学分析对确定暴露在环境中的风险的有用性 化学制品。

SUMMARY The long term goal of this project is to discover xenobiotics that contribute to preterm birth, relying on nontargeted chemical analysis by mass spectrometry. The study is focused on Puerto Rico because the incidence of preterm birth there is the second highest in the world. Three types of samples will be studied: urine, placenta and water. There are five Specific Aims. Specific Aim 1 concerns the urine samples, and studies the hypothesis that preterm urines in Puerto Rico contain a different exposome (xenobiotics or in vivo environmental chemical exposure) than term urines. For this Specific Aim, a large volume (0.5 gallon) of urine as an accumulation of early morning voids is being collected from each pregnant woman, which then is extracted with a porous extraction paddle (stirring "tea bag" filled with 2.0 g of particulate adsorbents). This new technique yields a convenient repository sample (the bag) for shipment, storage, and analysis of aliquots. Specific Aim 2 addresses placenta, since it is the target tissue for postulated environmental chemicals that contribute to preterm birth. Here the hypothesis is that the exposome of women in Puerto Rico (preterm birth rate 17.7%) is different qualitatively or quantitatively than in Boston (preterm birth rate 10.7%). In this Specific Aim, both the organic extractable exposome, and the exposome that has formed DNA adducts, will be tested in placenta. This Specific Aim helps to deal with the possibility that preterm birth is high in Puerto Rico because the exposomes of pregnant women there are high in general without any differences between preterm and term women. Specific Aim 3 focuses on placental cell cultures subjected to oxidative stress and inflammation (that can be caused by xenobiotics), and seeks to learn whether DNA adducts in these stressed cultures are similar to those in preterm placenta from Puerto Rico. Specific Aim 4 seeks to identify pollutants in ground and tap water samples in Puerto Rico, and also corresponding pollutant degradation products when these samples are remediated in Project 5 by electrolysis. Specific Aim 5 proposes to increase the sensitivity, scope, and qualitative capability of current methods for nontargeted chemical analysis by advancing and incorporating derivatization by ionic tagging. The methodology of Specific Aim 5 will be used in the work on Specific Aims 1, 2 and 4. Overall, the project is significant in its potential to help reduce the incidence of preterm birth; in establishing and characterizing by mass spectrometry valuable repository samples from pregnant women from whom extensive demographic information is being collected; and in advancing the usefulness of nontargeted chemical analysis in general for defining the risks from exposure to environmental chemicals.