CHEMICAL CARCINOGENESIS AND CELL PROLIFERATION
CHEMICAL CARCINOGENESIS AND CELL PROLIFERATION
批准号:
3165346
负责人:
David G. Kaufman
金额:
$13.91万
依托单位国家:
美国
项目类别:
财政年份:
1980
资助国家:
美国
项目状态:
已结题
起止时间:
1980-02-01 至 1987-12-31
关键词:
DNA methylation alkylating agents antibody autoradiography carcinogens cell population study chemical carcinogenesis density gradient ultracentrifugation electron microscopy gel electrophoresis molecular site mycotoxins nitrosamines nucleic acid sequence radiotracer synchronous cell division tissue /cell culture
中文摘要
这个研究项目的目的是研究分子
细胞增殖与细胞增殖之间关系的机制
化学致癌。它建议研究DNA如何以及在哪里
复制参与了细胞到细胞的多阶段转变
恶性表型。该项目的技术途径之一是
真核细胞复制复合体的分离
研究DNA的体外复制并探讨其作用机制
化学致癌物。努力的方向将是进一步
真核细胞化学成分的纯化与鉴定
复制复合体,分析致癌物对活性的影响
体外复制复合体的研究和DNA序列的分离
在S阶段的早期复制。复制复合体上的DNA是
优先被化学致癌物甲基化,这是由于
复制叉子对化学烷基化的敏感性更高。这个
负责这一现象的机制将被调查。
此外,这种观察结果相对于其他观察结果的一般性
致癌物质将得到验证。此项目中的另一种技术方法
DNA加合物的体外定位是借助特异的
抗体和电子显微镜。这将使我们能够研究
复制叉与致癌物损伤和提供
通过复制洞察病变旁路的机制
机械设备。这个项目的研究是为了更好地
对细胞转化的生物化学和生物化学的认识
导致癌症发生的机制。长期的
上述研究的目的是阐明较高频率的
细胞经致癌物处理后,出现S期细胞转化现象。
英文摘要
The objective of this research project is to investigate the molecular
mechanisms underlying the relationship between cell proliferation and
chemical carcinogenesis. It proposes to study how and where DNA
replication is involved in the multi-stage transition of a cell to the
malignant phenotype. One of the technical approaches of this project is
the isolation of eukaryotic replication complexes which can be used to
study DNA replication in vitro as well as to probe the mechanisms of action
of chemical carcinogens. Efforts will be directed towards further
purification and characterization of the constituents of the eukaryotic
replication complex, analysis of the effect of carcinogens on the activity
of replication complexes in vitro and isolation of DNA sequences that
replicate early in the S phase. DNA at the replication complex is
preferentially methylated by chemical carcinogens and this is due to a
higher susceptibility of replication forks to chemical alkylation. The
mechanisms responsible for this phenomemon will be investigated.
Furthermore, the generality of such observations in relation to other
carcinogens will be verified. Another technical approach in this project
is the in vitro localization of DNA adducts with the help of specific
antibodies and the electron microscope. This will allow the study of the
relationship between replication forks and carcinogen damage and provide
insight about the mechanisms of lesion bypass by the replication
machinery. The studies in this project are directed towards a better
understanding of the biochemistry of cell transformation and the biological
mechanisms responsible for the initiation of cancer. The long-term
objective of the above studies is to elucidate the higher frequency of
transformation observed when cells are treated with carcinogens in S phase.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Confocal Laser Scanning Microscope LSM 710 #5
-
批准号:7595557
-
项目类别:
-
资助金额:$44.92万
-
财政年份:2009
-
负责人:David G. Kaufman
-
依托单位:
Identification of Areas of Oxidative Damage in Human Genomic DNA
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批准号:7193167
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项目类别:
-
资助金额:$16.43万
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财政年份:2007
-
负责人:David G. Kaufman
-
依托单位:
FASEB Summer Conference on Nuclear Structure and Cancer
-
批准号:7426335
-
项目类别:
-
资助金额:$0.75万
-
财政年份:2007
-
负责人:David G. Kaufman
-
依托单位:
Identification of Areas of Oxidative Damage in Human Genomic DNA
-
批准号:7440180
-
项目类别:
-
资助金额:$16.43万
-
财政年份:2007
-
负责人:David G. Kaufman
-
依托单位:
Transformation of Human Endometrial Epithelial Cells
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批准号:6868849
-
项目类别:
-
资助金额:$13.14万
-
财政年份:2004
-
负责人:David G. Kaufman
-
依托单位:
Transformation of Human Endometrial Epithelial Cells
-
批准号:6709781
-
项目类别:
-
资助金额:$13.14万
-
财政年份:2004
-
负责人:David G. Kaufman
-
依托单位:
Estrogens, Paracrine Factors, and Endometrial Cancer
-
批准号:6612583
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项目类别:
-
资助金额:$25.9万
-
财政年份:2003
-
负责人:David G. Kaufman
-
依托单位:
Estrogens, Paracrine Factors, and Endometrial Cancer
-
批准号:7032997
-
项目类别:
-
资助金额:$25.29万
-
财政年份:2003
-
负责人:David G. Kaufman
-
依托单位:
Estrogens, Paracrine Factors, and Endometrial Cancer
-
批准号:6888497
-
项目类别:
-
资助金额:$25.9万
-
财政年份:2003
-
负责人:David G. Kaufman
-
依托单位:
Estrogens, Paracrine Factors, and Endometrial Cancer
-
批准号:6743952
-
项目类别:
-
资助金额:$25.9万
-
财政年份:2003
-
负责人:David G. Kaufman
-
依托单位:
Confocal Laser Scanning Microscope
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批准号:6581666
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项目类别:
-
资助金额:$33.38万
-
财政年份:2003
-
负责人:David G. Kaufman
-
依托单位:
CANCER SUSCEPTIBILITY AND S PHASE INITIATION SITES
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批准号:6514322
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项目类别:
-
资助金额:$27.45万
-
财政年份:2000
-
负责人:David G. Kaufman
-
依托单位:
CANCER SUSCEPTIBILITY AND S PHASE INITIATION SITES
-
批准号:6192918
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项目类别:
-
资助金额:$28.87万
-
财政年份:2000
-
负责人:David G. Kaufman
-
依托单位:
CANCER SUSCEPTIBILITY AND S PHASE INITIATION SITES
-
批准号:6633604
-
项目类别:
-
资助金额:$28.14万
-
财政年份:2000
-
负责人:David G. Kaufman
-
依托单位:
Cancer Susceptibility and S Phase Initiation Sites
-
批准号:7371150
-
项目类别:
-
资助金额:$26.78万
-
财政年份:2000
-
负责人:David G. Kaufman
-
依托单位:
CANCER SUSCEPTIBILITY AND S PHASE INITIATION SITES
-
批准号:6377715
-
项目类别:
-
资助金额:$26.78万
-
财政年份:2000
-
负责人:David G. Kaufman
-
依托单位:
Cancer Susceptibility and S Phase Initiation Sites
-
批准号:7578953
-
项目类别:
-
资助金额:$26.78万
-
财政年份:2000
-
负责人:David G. Kaufman
-
依托单位:
Cancer Susceptibility and S Phase Initiation Sites
-
批准号:6920930
-
项目类别:
-
资助金额:$28.24万
-
财政年份:1999
-
负责人:David G. Kaufman
-
依托单位:
Cancer Susceptibility and S Phase Initiation Sites
-
批准号:7225216
-
项目类别:
-
资助金额:$26.78万
-
财政年份:1999
-
负责人:David G. Kaufman
-
依托单位:
Cancer Susceptibility and S Phase Initiation Sites
-
批准号:7050621
-
项目类别:
-
资助金额:$27.58万
-
财政年份:1999
-
负责人:David G. Kaufman
-
依托单位:
海外基金