Characterization of Naphthalene DNA Adducts in Mice and Firefighters

小鼠和消防员中萘 DNA 加合物的表征

基本信息

  • 批准号:
    10462039
  • 负责人:
  • 金额:
    $ 4.68万
  • 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:
    2022-09-01 至 2024-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract Naphthalene (NA), a simple polycyclic aromatic hydrocarbon, is persistently present in the environment as a byproduct of combustion of fossil fuels and burning of tobacco and other products. Its ubiquitous presence results in widespread exposure to the general population. Certain occupational groups, such as firefighters, have elevated levels of exposure. Firefighters also have increased incidences of certain types of cancer. NA is currently classified by the International Agency for Research on Cancer (IARC) as a Class 2B Carcinogen. There is direct evidence of tumor formation in mice and rats but no direct evidence of carcinogenecity of NA in humans at this time. The pathogenesis of tumor formation in mice and rats after exposure to NA is unclear; cytotoxic and genotoxic mechanisms are both proposed in the current literature. NA metabolism results in the generation of reactive intermediates such as 1,2-epoxide and reactive metabolites such as 1,4- and 1,2- naphthoquinone (NAQ). Reactive quinone and epoxide metabolites of similar compounds, such as benzo[a]pyrene, have been shown to enact their carcinogenecity through DNA adduct formation. Published ex vivo and in vitro data have demonstrated that NA metabolites can form adducts with DNA. The objective of this study is to identify and quantify NA-DNA adducts in mouse lung as well as mouse and human blood to enable assessment of potential genotoxicity in firefighters. Several hypotheses will be tested: 1) Circulating reactive NA metabolites, particularly NAQs, will form stable as well as depurinating adducts with DNA in both lung tissue and blood leukocytes in vivo; 2) the types and abundances of NA-DNA adducts in circulating leukocytes will at least partly reflect adduct formation in the lung; 3) the types of NA-DNA adducts detected in circulating leukocytes from exposed mice and firefighters will be similar; and 4) exposure to fire smoke will increase NA- DNA adduct levels in firefighters. These hypotheses will be tested through the application of 3 Specific Aims. In Aim 1, I will Identify and quantitate NA-DNA adducts formed in wild-type (WT) mice following NA inhalation exposure, with use of mass spectrometry methods. In Aim 2, I will dissect metabolic pathways responsible for NA-DNA adduct formation in the lung and circulating leukocytes of NA-exposed mice, with use of unique transgenic mouse models (liver-Cpr-null, liver-Ephx1-null, and Cyp2abfgs-null). In Aim 3, I will characterize NA-DNA adducts in blood specimens from firefighters and control donors. This project will provide direct evidence for the formation of NA-DNA adducts in vivo, lay the foundation for future studies of the genotoxicity of NA, obtain evidence to support more extensive assessments of the carcinogenic risks of NA to firefighters, and could have direct implications for the general population. Through the execution of this project and the help of this fellowship, I will be fully trained in scientific and professional skills necessary for my career advancement as an independent researcher in academia.
项目总结/文摘

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 }}

Sarrah Hannon其他文献

Sarrah Hannon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('Sarrah Hannon', 18)}}的其他基金

Characterization of Naphthalene DNA Adducts in Mice and Firefighters
小鼠和消防员中萘 DNA 加合物的表征
  • 批准号:
    10707915
  • 财政年份:
    2022
  • 资助金额:
    $ 4.68万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
  • 批准号:
    2230829
  • 财政年份:
    2023
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 4.68万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了