BIOALKYLATION IN CHEMICAL CARCINOGENESIS
化学致癌作用中的生物烷基化
基本信息
- 批准号:3189116
- 负责人:
- 金额:$ 14.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1987
- 资助国家:美国
- 起止时间:1987-09-30 至 1996-03-31
- 项目状态:已结题
- 来源:
- 关键词:DNA S adenosylmethionine alkyl group alkylation anthracenes benzanthracenes benzopyrenes carbopolycyclic compound carcinogen testing carcinosarcoma chemical carcinogen chemical carcinogenesis chemical structure function chrysenes cytoplasm diol epoxides gas chromatography high performance liquid chromatography hydrolysis laboratory rat mass spectrometry methylation methyltransferase nuclear magnetic resonance spectroscopy oxidation pyrenes tissue /cell culture toxin metabolism
项目摘要
The objectives of this biochemical research are 1) to critically test the
structure-activity relationship theory developed in this laboratory over
the past 20 years, 2) to increase our understanding of the nature of the
reactions that are involved in the metabolic activation of polynuclear
aromatic hydrocarbons, and 3) to understand the reasons for the striking
structure-activity relationships in this class of compounds. The
metabolism of a series of closely related hydrocarbons will be investigated
and compared, using HPLC, GC/MS, and 32P postlabelling and a number of
reference compounds, and their activation to electrophilic intermediates
that react with nucleic acids will be studied, in vitro and in vivo, in rat
liver, lung, and subcutaneous tissue. We expect to be able to distinguish
between the reactions of the hydrocarbons leading to carcinogenesis and the
reactions leading to inactivation. The long term objectives of these
studies are 1) to correctly predict the carcinogenicity of a polynuclear
aromatic hydrocarbon from a knowledge of its features of structure and
metabolism, and 2) to assess, in metabolism studies, the susceptibility of
subcutaneous tissue, in comparison with lung and liver, to carcinogenesis
by polynuclear aromatic hydrocarbons. A more complete understanding of the
most important structural features and reactions involved in polynuclear
aromatic hydrocarbon carcinogenesis may eventually lead to methods for the
prevention of some of the human cancer that is currently considered to be
caused by this class of chemical carcinogens.
这项生化研究的目标是 1) 严格测试
本实验室发展的构效关系理论
过去20年,2)增加我们对事物本质的理解
参与多核代谢活化的反应
芳香烃,以及 3) 了解造成这一惊人现象的原因
此类化合物的构效关系。 这
将研究一系列密切相关的碳氢化合物的代谢
并使用 HPLC、GC/MS 和 32P 后标记以及许多方法进行比较
参考化合物及其对亲电子中间体的活化
与核酸反应的物质将在大鼠体内和体外进行研究
肝、肺和皮下组织。 我们期望能够区分
碳氢化合物的致癌反应与致癌反应之间的关系
导致失活的反应。 这些的长期目标
研究目的 1) 正确预测多核物质的致癌性
芳香烃从其结构特征和
代谢,以及 2) 在代谢研究中评估
皮下组织与肺和肝相比,更容易致癌
由多核芳香烃。 更全面的了解
多核反应中最重要的结构特征和反应
芳香烃致癌作用最终可能导致找到治疗方法
预防目前被认为是最重要的一些人类癌症
由此类化学致癌物引起。
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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James W Flesher其他文献
James W Flesher的其他文献
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{{ truncateString('James W Flesher', 18)}}的其他基金
DMBA DERVIVATIVES AND CHEMICAL CARCINOGENESIS
DMBA 衍生物与化学致癌作用
- 批准号:
2910995 - 财政年份:1999
- 资助金额:
$ 14.91万 - 项目类别:
DMBA DERVIVATIVES AND CHEMICAL CARCINOGENESIS
DMBA 衍生物与化学致癌作用
- 批准号:
6377577 - 财政年份:1999
- 资助金额:
$ 14.91万 - 项目类别:
DMBA DERVIVATIVES AND CHEMICAL CARCINOGENESIS
DMBA 衍生物与化学致癌作用
- 批准号:
6514365 - 财政年份:1999
- 资助金额:
$ 14.91万 - 项目类别:
DMBA DERVIVATIVES AND CHEMICAL CARCINOGENESIS
DMBA 衍生物与化学致癌作用
- 批准号:
6175308 - 财政年份:1999
- 资助金额:
$ 14.91万 - 项目类别:
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