Carcinogenic tobacco-specific nitrosamines induction of apurinic/apyrimidinic sites in DNA of human oral cells
致癌烟草特异性亚硝胺诱导人类口腔细胞 DNA 中的无嘌呤/无嘧啶位点
基本信息
- 批准号:10558698
- 负责人:
- 金额:$ 0.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-31 至 2023-01-02
- 项目状态:已结题
- 来源:
- 关键词:4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol4-(methylnitrosamino)-1-(3-pyridyl)-1-butanoneAcroleinBase SequenceBiological MarkersCancer EtiologyCarcinogensCardiovascular DiseasesCellsChemicalsCigaretteCigarette SmokerClassificationDNADNA AdductionDNA AdductsDNA DamageDNA RepairDataDeoxyguanosineDeoxyribonucleosidesDerivation procedureDiseaseDoseElectronic cigaretteExcisionExcision RepairExposure toFosteringGenomic InstabilityGoalsHabitsHealthHomeostasisHumanHydrolysisHydroxylamineIn VitroInternational Agency for Research on CancerInvestigationLeukocytesLinkLiquid ChromatographyLiverLocationLungLung diseasesMalignant NeoplasmsMalignant neoplasm of esophagusMalignant neoplasm of lungMalignant neoplasm of pancreasMembraneMetabolic ActivationMethodsMorphologic artifactsMucous MembraneMutationN&apos-nitrosonornicotineNitrosaminesOralOral cavityOral mucous membrane structureOropharyngealPredispositionPreventionProbabilityProcessPurinesPyrimidineRattusReactionSiteSmokeless TobaccoSmokerStructure of mucous membrane of noseSurvival RateTissuesTobaccoTobacco useTobacco-Associated CarcinogenTobacco-Related CarcinomaUnited Statesadductage effectanalytical methodbasecancer preventioncancer riskcarcinogenicitycigarette smokecigarette smoke-inducedcigarette smokingcytotoxicdesignelectronic cigarette userepidemiologic dataepidemiology studyexposed human populationgenotoxicityhuman DNAin vivomalignant mouth neoplasmnon-smokeroral cancer preventionpreventresponsesilochromesmokeless tobacco usersmoking cessationtandem mass spectrometrytobacco exposuretobacco productstobacco userurinary
项目摘要
Project Summary
Cigarette smoking is the leading cause of lung and oral cancer in the United States. Smokeless tobacco causes
cancer of the mouth, esophagus and pancreas. The health effects of e-cigarettes are still under investigation but
may disturb oral cavity homeostasis and cause lung and cardiovascular diseases. The tobacco-specific
nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are
classified as human carcinogens by the International Agency for Research on Cancer, and are recognized
causes of these diseases. Metabolic activation of NNK and NNN results in formation of reactive electrophiles
that modify DNA to produce a variety of products such as N7-[4-(3-pyridyl)-4-oxobut-1-yl]-deoxyguanosine
(N7POBdG) that can result in apurinic/apyrimidinic (AP) sites in DNA by facile hydrolysis of the base-
deoxyribonucleoside bond; other tobacco constituents may also induce AP sites. AP site accumulation may
initiate the carcinogenic process. Oral cells provide the direct link between tobacco use and oral cancer in
humans and elevated DNA damage has been found in oral cells of tobacco users. We propose to analyze AP
sites in oral cell DNA with two specific aims: to develop a highly sensitive mass spectrometric method to quantify
AP sites in human oral cell DNA, and to quantify AP sites in oral cell DNA induced by cigarette smoke, smokeless
tobacco and e-cigarettes. The goals are to establish oral cell DNA AP sites as biomarkers of tobacco induced
DNA damage in cigarette smokers, smokeless tobacco users, and e-cigarette users, and to ultimately identify
susceptible tobacco users and design effective strategies to prevent cancer. This study may also provide
preliminary data for a large epidemiologic study. We have strong preliminary data to support this proposal.
项目摘要
吸烟是美国肺癌和口腔癌的主要原因。无烟烟草导致
口腔、食道和胰腺癌。电子烟对健康的影响仍在调查中,
可能扰乱口腔内环境稳定,引起肺和心血管疾病。烟草特异性
亚硝胺4-(甲基亚硝胺基)-1-(3-吡啶基)-1-丁酮(NNK)和N '-亚硝基去甲烟碱(NNN)是
被国际癌症研究机构列为人类致癌物,并被公认为
这些疾病的原因。NNK和NNN的代谢活化导致反应性亲电体的形成
其修饰DNA以产生多种产物,例如N7-[4-(3-吡啶基)-4-氧代丁-1-基]-脱氧鸟苷
(N7 POBdG),其可通过碱基的容易水解在DNA中产生脱嘌呤/脱嘧啶(AP)位点,
其他烟草成分也可能诱导AP位点。AP部位蓄积可能
启动致癌过程。口腔细胞提供了烟草使用和口腔癌之间的直接联系,
在烟草使用者的口腔细胞中发现了DNA损伤的增加。我们建议分析AP
口腔细胞DNA中的位点,有两个具体目标:开发一种高灵敏度的质谱方法,
人口腔细胞DNA中的AP位点,并定量香烟烟雾诱导的口腔细胞DNA中的AP位点,
烟草和电子烟。目的是建立口腔细胞DNA AP位点作为烟草诱导的
吸烟者、无烟烟草使用者和电子烟使用者的DNA损伤,并最终确定
烟草使用者和设计有效的策略来预防癌症。这项研究还可以提供
一项大型流行病学研究的初步数据。我们有强有力的初步数据支持这一提议。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jiehong Guo其他文献
Jiehong Guo的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Jiehong Guo', 18)}}的其他基金
Carcinogenic tobacco-specific nitrosamines induction of apurinic/apyrimidinic sites in DNA of human oral cells
致癌烟草特异性亚硝胺诱导人类口腔细胞 DNA 中的无嘌呤/无嘧啶位点
- 批准号:
10856299 - 财政年份:2023
- 资助金额:
$ 0.58万 - 项目类别:
Carcinogenic tobacco-specific nitrosamines induction of apurinic/apyrimidinic sites in DNA of human oral cells
致癌烟草特异性亚硝胺诱导人类口腔细胞 DNA 中的无嘌呤/无嘧啶位点
- 批准号:
10359388 - 财政年份:2022
- 资助金额:
$ 0.58万 - 项目类别:
相似海外基金
Project 2 - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) α-Hydroxy Glucuronides, Metabolic Profiling and Activation
项目 2 - 4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮 (NNK) α-羟基葡萄糖醛酸、代谢分析和激活
- 批准号:
9149449 - 财政年份:2010
- 资助金额:
$ 0.58万 - 项目类别:
The roles of different cytochrome P450 isozymes and prostagladin H synthase in pulmonary microsomal 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) biotransformation
不同细胞色素P450同工酶和前列腺素H合酶在肺微粒体4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮(NNK)生物转化中的作用
- 批准号:
303377-2004 - 财政年份:2004
- 资助金额:
$ 0.58万 - 项目类别:
Postgraduate Scholarships - Master's
Project 2 - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) α-Hydroxy Glucuronides, Metabolic Profiling and Activation
项目 2 - 4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮 (NNK) α-羟基葡萄糖醛酸、代谢分析和激活
- 批准号:
9769641 - 财政年份:
- 资助金额:
$ 0.58万 - 项目类别: