Project 1: Discovery of Xenobiotics Associated with Preterm Birth
项目1:与早产相关的异生素的发现
基本信息
- 批准号:7936551
- 负责人:
- 金额:$ 29.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-04-12 至 2014-03-31
- 项目状态:已结题
- 来源:
- 关键词:ApoptosisAttentionBiologicalBiological AssayCell Culture TechniquesComplexComplex MixturesCultured CellsDNA AdductsData AnalysesDetectionElectrolysesGoalsHome environmentHumanHuman ResourcesIncidenceInflammationLaboratoriesLeukocytesMass Spectrum AnalysisMedicalMembraneMetabolismMethodologyMethodsMonitorNucleotidesOxidative StressPlacentaPregnancyPremature BirthPuerto RicoRattusReactive Oxygen SpeciesSamplingScreening procedureSiteSuperfundTerm BirthTestingTissuesUrineWaterWomanXenobioticsbasebirth controlcytotoxicityexperiencegenotoxicityground waterimprovedin vivomass spectrometermeetingsoxidationperipheral bloodprogramsremediationsuperfund site
项目摘要
Preterm birth is a major medical problem of increasing incidence, and xenobiotics may contribute. The longterm goal of this project is to discover xenobiotics that contribute to preterm birth. Environmental and biological samples will be tested, and these samples will mostly come from Puerto Rico because of the unusually high incidence of preterm birth there. While nontargeted (screening) analysis will be conducted, primary attention will be given to Superfund and related contaminants, since there are many Superfund sites in Puerto Rico. Much of the analysis will be based on mass spectrometry (MS); three types of MS will be employed: (HPLC)MALDI-TOF/TOF-MS, GC-EI(EC)-TOF-MS, and HPLC-ESI-TOF-MS. We will seek to discover "putative PTB-xenobiotics," defined as xenobiotics that meet either one of the following two criteria:
they correlate with preterm birth, or they do not but are common as contaminants and have a bioactivity that could contribute to this condition. The environmental samples will be tap water and ground water, including samples that have been remediated (detoxified) by electrolysis. The biological samples will be pregnancy tissues (gestational membrane, placenta), cell cultures, peripheral blood leukocytes and urine. The pregnancy tissues will come from rats and humans, and the leukocytes and urine will come from humans.
One or more of four kinds of assays will be applied to each of these types of samples: 1. Direct Detection, the xenobiotic (or a laboratory derivative thereof) is directly detected in a mass spectrometer; 2. DNA Adduct, the xenobiotic forms a DNA adduct in vivo that is detected by Mass Tag Profiling; 3. Pro-oxidant, the xenobiotic is detected after metabolism-like oxidation in a Nucleotide Exposure Assay; 4. Bioassay, the xenobiotic is detected in a bioassay with cultured cells derived from human placenta¿based initially on monitoring for cytotoxicity (primary screen) and subsequently for apoptosis, genotoxicity, inflammation, and oxidative stress (secondary screen, reflecting mechanisms that could contribute to preterm birth). New or improved analytical methodology will be developed, and new combinations of methodology will be studied in this project to enhance the discovery of putative PTB-xenobiotics by these four strategies. The project, thereby, will result in generally-applicable advances in the overall field of discovering toxic xenobiotics in complex samples. Through exchange of samples, collaborative testing, and collaborative analysis of data,
either directly or through the cores, this project integrates with all of the other projects in the PRoTECT
program.
早产是一个主要的医学问题,发病率不断上升,外源性物质可能会起作用。该项目的长期目标是发现导致早产的外源性物质。将对环境和生物样本进行检测,这些样本将主要来自波多黎各,因为那里的早产发生率异常高。虽然将进行非目标(筛选)分析,但主要关注超级基金和相关污染物,因为波多黎各有许多超级基金场地。大部分分析将基于质谱(MS);将采用三种类型的MS:(HPLC)MALDI-TOF/TOF-MS、GC-EI(EC)-TOF-MS和HPLC-ESI-TOF-MS。我们将寻求发现“推定的PTB-异生物质”,定义为满足以下两个标准之一的异生物质:
它们与早产有关,或者它们与早产无关,但作为污染物是常见的,并且具有可能促成这种状况的生物活性。环境样品将是自来水和地下水,包括通过电解进行补救(解毒)的样品。生物样本将是妊娠组织(妊娠膜、胎盘)、细胞培养物、外周血白细胞和尿液。妊娠组织将来自大鼠和人类,白细胞和尿液将来自人类。
四种测定中的一种或多种将应用于这些类型的样品中的每一种:1.直接检测,在质谱仪中直接检测异生质(或其实验室衍生物); 2. DNA加合物,异生物质在体内形成DNA加合物,其通过质量标签分析检测; 3.促氧化剂,在核苷酸暴露测定中代谢样氧化后检测异生质; 4.生物测定,在生物测定中检测外源性物质,该生物测定使用来自人胎盘的培养细胞,最初基于对细胞毒性的监测(初步筛选),随后基于对细胞凋亡、遗传毒性、炎症和氧化应激的监测(二次筛选,反映可能导致早产的机制)。本项目将开发新的或改进的分析方法,并将研究新的方法组合,以通过这四种策略来加强推定的PTB-异生物质的发现。因此,该项目将导致在复杂样品中发现有毒异生物质的整个领域的普遍适用的进展。通过交换样品、协作测试和协作分析数据,
无论是直接还是通过核心,该项目都与PRoTECT中的所有其他项目相结合
程序.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('ROGER Wallace GIESE', 18)}}的其他基金
Project 3: Discovery of Xenobiotics Associated with Preterm Birth
项目3:与早产相关的异生素的发现
- 批准号:
8884316 - 财政年份:2010
- 资助金额:
$ 29.74万 - 项目类别:
Project 3: Discovery of Xenobiotics Associated with Preterm Birth
项目3:与早产相关的异生素的发现
- 批准号:
8831684 - 财政年份:2010
- 资助金额:
$ 29.74万 - 项目类别:
Project 3: Discovery of Xenobiotics Associated with Preterm Birth
项目3:与早产相关的异生素的发现
- 批准号:
8927935 - 财政年份:2010
- 资助金额:
$ 29.74万 - 项目类别:
Project 3: Discovery of Xenobiotics Associated with Preterm Birth
项目3:与早产相关的异生素的发现
- 批准号:
8649397 - 财政年份:2010
- 资助金额:
$ 29.74万 - 项目类别:
Project 3: Discovery of Xenobiotics Associated with Preterm Birth
项目3:与早产相关的异生素的发现
- 批准号:
9249553 - 财政年份:2010
- 资助金额:
$ 29.74万 - 项目类别:
Discovery of Genotoxic Biomarkers in Urine for Cancer
尿液中癌症基因毒性生物标志物的发现
- 批准号:
6743420 - 财政年份:2003
- 资助金额:
$ 29.74万 - 项目类别:
Discovery of Genotoxic Biomarkers in Urine for Cancer
尿液中癌症基因毒性生物标志物的发现
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6803564 - 财政年份:2003
- 资助金额:
$ 29.74万 - 项目类别:
CATION LABELING MASS SPECTROMETRY OF DNA ADDUCTS
DNA 加合物的阳离子标记质谱分析
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6055755 - 财政年份:2000
- 资助金额:
$ 29.74万 - 项目类别:
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