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

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.
项目总结

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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Jiehong Guo其他文献

Jiehong Guo的其他文献

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{{ 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:

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  • 批准号:
    9149449
  • 财政年份:
    2010
  • 资助金额:
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  • 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:
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  • 财政年份:
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