IN VIVO OXIDATIVE DNA DAMAGE IN CULTURED MAMMALIAN CELLS
培养哺乳动物细胞体内 DNA 氧化损伤
基本信息
- 批准号:3421574
- 负责人:
- 金额:$ 15.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1991
- 资助国家:美国
- 起止时间:1991-08-06 至 1994-08-05
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Oxygen free radicals are believed to be among the major possible
causative agents of a number of pathological conditions such as cancer,
aging, arthritis, emphysema and infant retinopathy among others. One
mode of action of oxygen-derived species is to cause DNA lesions,
resulting in cell mutation or death. The goal of this study is to
quantitatively establish the extent to which oxygen free radicals are
responsible for in vivo DNA damage in cultured mammalian cells. A model
murine hybridoma system producing monoclonal IgG antibodies has been
chosen for our studies. In order to attain our objective, the following
specific questions will be answered sequentially:
i) Can oxidative DNA lesions be quantitatively measured in
chromatin? Contemporary measurements of chemical modifications to DNA
have been made on isolated DNA, which do not portray a realistic picture
of actual damage occurring at the chromatin level. This is because DNA
present in chromatin is structurally sequestered and bound to histones.
Furthermore, present state-of-the-art measurements of DNA damage in
mammalian cells consist primarily of identifying strand breakage. There
is a need for a more powerful and quantitative assay. A superior
approach is available through the use of Gas Chromatography/Mass
Spectrometry techniques to precisely and quantitatively identify DNA
lesions. Several base products have been identified through this
technique by exposing isolated DNA to free radical attack. It is
proposed to expose isolated intact chromatin to free radical attack under
controlled conditions and subsequently characterize the damage.
ii) Are the same lesions found in cells in vivo? This question
has not been addressed to any significant degree in mammalian cells. We
propose to use in vitro bioreactor culture techniques, which allow for
the precise control of all environmental and physiological factors. Live
cells in controlled environments will be exposed (as in the case of
isolated chromatin) to known free radical generating systems. Based on
the methodology developed to answer the first question, this approach
will permit accurate studies of in vivo DNA damage in cultured mammalian
cells. Additionally, it will be possible to study the kinetics of DNA
repair by monitoring the temporal disappearance of damaged bases from
cellular chromatin after exposing cells to free radicals.
In addition to having a major impact on contemporary research
in the field of oxygen toxicity, this work will assist in meeting the
objectives of the RFA by not only developing hybridomas as a high
connectivity mammalian system but also in promoting the use of in vitro
tissue culture experiments as an alternative to animal use. In the
longer term, the studies proposed here will lay the groundwork for
understanding conditions and mechanisms by which oxidative DNA damage and
subsequent repair occurs in mammalian cells.
氧自由基被认为是可能的主要原因之一
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Non-contact Optical Temperature Sensor for Neonatal Monitoring.
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- 批准号:
7978611 - 财政年份:2010
- 资助金额:
$ 15.65万 - 项目类别:
Non-contact Optical Temperature Sensor for Neonatal Monitoring.
用于新生儿监测的非接触式光学温度传感器。
- 批准号:
8099702 - 财政年份:2010
- 资助金额:
$ 15.65万 - 项目类别:
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低成本高通量细胞培养装置
- 批准号:
6764599 - 财政年份:2004
- 资助金额:
$ 15.65万 - 项目类别:
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- 资助金额:
$ 15.65万 - 项目类别:
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用于荧光传感的蓝光发光二极管
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6315386 - 财政年份:2000
- 资助金额:
$ 15.65万 - 项目类别:
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