Project 3: Discovery of Xenobiotics Associated with Preterm Birth

总结 该项目的长期目标是发现导致早产的外源性物质， 通过质谱法进行非靶向化学分析。这项研究的重点是波多黎各，因为 早产率居世界第二位。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 研究了波多黎各早产儿尿液中含有不同的代谢物组（外源性或体内）的假设， 环境化学品暴露）比长期尿液。对于此特定目标，大量（0.5加仑）尿液 因为从每个孕妇那里收集了清晨的排泄物， 用多孔提取桨（搅拌填充有2.0g颗粒吸附剂的“茶袋”）提取。这 新技术产生了一个方便的储存库样品（袋），用于运输、储存和等分试样分析。 具体目标2涉及胎盘，因为它是假定环境化学品的靶组织， 导致早产。这里的假设是，波多黎各妇女的麻烦（早产 出生率17.7%）与波士顿（早产率10.7%）在质量或数量上有所不同。在这一具体 目的是，有机可提取的DNA组和已形成DNA加合物的DNA组都将在 胎盘这一具体目标有助于解决波多黎各早产率高的可能性，因为 那里的孕妇的体重一般都很高，早产和早产之间没有任何差异。 术语女人具体目标3侧重于受到氧化应激和炎症的胎盘细胞培养 (that可能是由外源性物质引起的），并试图了解这些应激培养物中的DNA加合物是否 与来自波多黎各的早产胎盘中的那些相似。具体目标4旨在确定地下污染物 和自来水样品在波多黎各，以及相应的污染物降解产物时，这些 在项目5中，通过电解对样品进行了补救。具体目标5建议提高灵敏度， 范围和定性能力的非靶向化学分析， 结合通过离子标记的衍生化。具体目标5的方法将用于 具体目标1、2和4。总的来说，该项目在帮助减少 早产;在建立和表征质谱宝贵的储存库样品， 正在收集其广泛人口资料的孕妇;以及 一般非目标化学分析对确定暴露于环境污染的风险的有用性 化学品

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.