Formaldehyde Genotoxicity
甲醛的遗传毒性
基本信息
- 批准号:8825496
- 负责人:
- 金额:$ 39.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-06-29 至 2016-03-31
- 项目状态:已结题
- 来源:
- 关键词:AbbreviationsAddressAdultAlkylating AgentsAnimalsBiologicalCD34 geneCarcinogensCell physiologyCellsChemicalsChromosomal BreaksChromosomal translocationChromosome BreakageComplexDNADNA DamageDNA Double Strand BreakDNA RepairDNA Repair DisorderDNA Sequence RearrangementDNA lesionDNA-protein crosslinkDoseDouble Strand Break RepairEpidemiologyEpigenetic ProcessEtiologyEventFormaldehydeGene MutationGenesGeneticGenetic MarkersGenomicsGuidelinesHistonesHumanHuman EngineeringImpairmentInjuryLeadLesionLinkLipid PeroxidationLocationMalignant NeoplasmsMammalian CellMetabolicMetabolic BiotransformationMetabolismModelingMolecularMutationMyeloid LeukemiaNonhomologous DNA End JoiningNoseNucleotide Excision RepairNucleotidesOccupationalOxidative StressPeptidesPharmaceutical PreparationsProcessPropertyResearchRiskRisk AssessmentRisk FactorsRodentRoleShuttle VectorsSiteSourceStem cellsSystemTissuesToxic Environmental SubstancesUncertaintyUpper respiratory tractWood materialamino acid metabolismbasecancer riskcarcinogenesiscarcinogenicitychromatin remodelingcrosslinkcytotoxiccytotoxicitydemethylationdesigngenotoxicityhigh riskhomologous recombinationhuman adult stem cellhuman tissueimprovedleukemiarepairedtoxicant
项目摘要
DESCRIPTION (provided by applicant): Formaldehyde (FA) is a ubiquitous environmental and occupational toxicant that is associated with an increasing number of human cancers. FA is also generated endogenously as a product of lipid peroxidation, drug biotransformation and several normal metabolic processes, such as histone demethylation during chromatin remodeling. Molecular mechanisms of FA carcinogenicity are poorly understood, in part reflecting its past association only with rare nasal cancers. A growing list of human cancers recently linked to FA exposure is difficult to explain by the cytotoxicity-based risk assessment models developed for nasal cancers in rodents. This application is designed to address major research gaps that hinder mechanistic understanding of FA-induced carcinogenic effects. Three specific aims are proposed to (1) determine main causes of FA mutagenicity in human cells, (2) identify genomic sites and genes that are prone to large rearrangements and (3) examine a role of epigenetic injury in the formation of large genetic changes by FA in human adult stem cells. A successful completion of these studies can lead to the identification of the mechanistically important biomarkers of genetic damage by FA and help resolve current uncertainties regarding its mode of carcinogenic action and ability to initiate leukemogenic events.
描述(由申请人提供):甲醛(FA)是一种普遍存在的环境和职业毒物,与越来越多的人类癌症有关。FA也是内源性产生的,作为脂质过氧化、药物生物转化和几种正常代谢过程的产物,例如染色质重塑期间的组蛋白去甲基化。FA致癌性的分子机制知之甚少,部分反映了其过去仅与罕见的鼻癌相关。最近越来越多的人类癌症与FA暴露有关,这很难用啮齿动物鼻癌的细胞毒性风险评估模型来解释。该应用程序旨在解决阻碍FA诱导的致癌作用的机械理解的主要研究空白。提出了三个具体目标:(1)确定人细胞中FA致突变性的主要原因,(2)鉴定易于发生大重排的基因组位点和基因,以及(3)检查表观遗传损伤在人成体干细胞中FA形成大遗传变化中的作用。这些研究的成功完成,可以导致识别的遗传损伤的重要生物标志物的FA和帮助解决目前的不确定性,其致癌作用的模式和能力,启动白血病事件。
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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Anatoly Zhitkovich其他文献
Anatoly Zhitkovich的其他文献
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{{ truncateString('Anatoly Zhitkovich', 18)}}的其他基金
Indirect Genotoxicity in Metal Carcinogenesis
金属致癌过程中的间接遗传毒性
- 批准号:
10527323 - 财政年份:2020
- 资助金额:
$ 39.92万 - 项目类别:
Indirect Genotoxicity in Metal Carcinogenesis
金属致癌过程中的间接遗传毒性
- 批准号:
10304906 - 财政年份:2020
- 资助金额:
$ 39.92万 - 项目类别:
Regulation of p53 and Checkpoint Signaling by Chromium(VI)
Chromium(VI) 对 p53 和检查点信号传导的调节
- 批准号:
10306386 - 财政年份:2017
- 资助金额:
$ 39.92万 - 项目类别:
Regulation of p53 and Checkpoint Signaling by Chromium(VI)
Chromium(VI) 对 p53 和检查点信号传导的调节
- 批准号:
10057383 - 财政年份:2017
- 资助金额:
$ 39.92万 - 项目类别:
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