A Targeted DNA Adductomics Approach for Analyzing > 100 DNA Adducts
用于分析 > 100 个 DNA 加合物的靶向 DNA 加合物组学方法
基本信息
- 批准号:10371133
- 负责人:
- 金额:$ 34.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-06-15 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAirAir PollutionAlkylating AgentsBiochemical GeneticsBiologicalBiological AssayBiological MarkersCell RespirationChemicalsCommunitiesDNADNA AdductionDNA AdductsDNA DamageDNA RepairDNA Repair GeneDNA analysisDNA biosynthesisDNA lesionDeoxyribonucleosidesDeoxyriboseDevelopmentEnvironmental ExposureEnvironmental PollutantsEnzymesExposure toGenetic TranscriptionGrantHealthHumanIndividualIonsKnowledgeLaboratoriesLibrariesLiquid ChromatographyMass Spectrum AnalysisMeasurementMetabolismMethodsMonitorMusMutagensOutcomeOxidative StressOxygenasesParticulate MatterPeptidesProtein AnalysisProteomicsReactionResearchRiskRunningSamplingScheduleSignal TransductionSourceStructure of parenchyma of lungTimeTissuesalpha ketoglutarateanalytical methodcrosslinkexperienceexposed human populationfine particlesgenetic approachgenetic informationgenetic manipulationgenotoxicityhigh throughput analysisimprovedinsightinterestnovelpublic health relevancerepairedtandem mass spectrometry
项目摘要
ABSTRACT
Endogenous metabolism and environmental exposure can give rise to DNA adduct formation. Robust
measurement of the levels of DNA adducts can offer important knowledge for understanding the mechanisms of
DNA repair and allow for assessment of human exposure to genotoxic chemicals. We reason that a scheduled
selected-reaction monitoring (SRM) method for DNA adduct analysis will facilitate high-throughput analysis of
the DNA adductome. The long-term objective of this application is to develop a targeted DNA adductomic assay
for assessing quantitatively the DNA adducts induced by various endogenous and exogenous sources of DNA
damaging agents, and to employ the method for monitoring human exposure to complicated environmental
pollutants and for investigating DNA repair. The proposed research is organized into three Specific Aims. In Aim
#1, we will establish an SRM library for targeted quantitative measurement of the DNA adductome. In Aim 2, we
will profile comprehensively the DNA adductome in lung tissues of mice exposed to particulate matter air
pollution. In Aim 3, we will assess the oxidative metabolism and repair of alkylated DNA lesions by Fe2+- and 2-
oxoglutarate-dependent oxygenases. The outcome of the proposed research will provide the scientific
community with a high-throughput platform that allows for monitoring the DNA adductome and will afford novel
insights about the repair of alkylated DNA lesions.
摘要
内源性代谢和环境暴露可引起DNA加合物的形成。鲁棒
DNA加合物水平的测量可以为理解
DNA修复和允许评估人类暴露于遗传毒性化学品。我们推断一个预定的
选择反应监测(SRM)方法的DNA加合物分析将有助于高通量分析,
DNA内收酶本申请的长期目标是开发一种靶向DNA内收体测定法,
用于定量评估由各种内源性和外源性DNA来源诱导的DNA加合物
有害物质,并采用该方法监测人类暴露于复杂的环境
污染物和研究DNA修复。本研究分为三个具体目标。在Aim中
#1,我们将建立SRM文库用于DNA内收体的靶向定量测量。在目标2中,
将全面分析暴露于颗粒物空气的小鼠肺组织中的DNA内收体
污染在目标3中,我们将评估Fe 2+和2-对烷基化DNA损伤的氧化代谢和修复,
酮戊二酸依赖性加氧酶。拟议研究的结果将提供科学的
社区的高通量平台,允许监测DNA内收体,并将提供新的
关于修复烷基化DNA损伤的见解。
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
HILIC-MS/MS for the Determination of Methylated Adenine Nucleosides in Human Urine.
- DOI:10.1021/acs.analchem.1c03829
- 发表时间:2021-12-28
- 期刊:
- 影响因子:7.4
- 作者:Guo C;Hu Y;Cao X;Wang Y
- 通讯作者:Wang Y
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Yinsheng Wang其他文献
Yinsheng Wang的其他文献
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{{ truncateString('Yinsheng Wang', 18)}}的其他基金
Chemical Biology of DNA and RNA Alkylation
DNA 和 RNA 烷基化的化学生物学
- 批准号:
10597056 - 财政年份:2020
- 资助金额:
$ 34.99万 - 项目类别:
Chemical Biology of DNA and RNA Alkylation
DNA 和 RNA 烷基化的化学生物学
- 批准号:
10376803 - 财政年份:2020
- 资助金额:
$ 34.99万 - 项目类别:
Chemical Biology of DNA and RNA Alkylation
DNA 和 RNA 烷基化的化学生物学
- 批准号:
10190950 - 财政年份:2020
- 资助金额:
$ 34.99万 - 项目类别:
Chemistry and Biology of Alkyl Phosphotriester Lesions
烷基磷酸三酯损伤的化学和生物学
- 批准号:
10520048 - 财政年份:2019
- 资助金额:
$ 34.99万 - 项目类别:
Chemistry and Biology of Alkyl Phosphotriester Lesions
烷基磷酸三酯损伤的化学和生物学
- 批准号:
9896297 - 财政年份:2019
- 资助金额:
$ 34.99万 - 项目类别:
Chemistry and Biology of Alkyl Phosphotriester Lesions
烷基磷酸三酯损伤的化学和生物学
- 批准号:
10307544 - 财政年份:2019
- 资助金额:
$ 34.99万 - 项目类别:
A Targeted DNA Adductomics Approach for Analyzing > 100 DNA Adducts
用于分析 > 100 个 DNA 加合物的靶向 DNA 加合物组学方法
- 批准号:
9883797 - 财政年份:2018
- 资助金额:
$ 34.99万 - 项目类别:
Quantitative Adductomics Approaches for Assessing the Occurrence and Repair of DNA Adducts
用于评估 DNA 加合物的发生和修复的定量加合物组学方法
- 批准号:
10172860 - 财政年份:2017
- 资助金额:
$ 34.99万 - 项目类别:
Quantitative Adductomics Approaches for Assessing the Occurrence and Repair of DNA Adducts
用于评估 DNA 加合物的发生和修复的定量加合物组学方法
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9389996 - 财政年份:2017
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Enzymatic Conversions of Tet-mediated Oxidation Products of 5-Methylcytosine
Tet 介导的 5-甲基胞嘧啶氧化产物的酶促转化
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8987741 - 财政年份:2015
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$ 34.99万 - 项目类别:
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