RESPONSE TO DNA DAMAGE--COLON VS SMALL INTESTINE
RESPONSE TO DNA DAMAGE--COLON VS SMALL INTESTINE
批准号:
6512984
负责人:
JOANNE R LUPTON
金额:
$22.68万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1994
资助国家:
美国
项目状态:
已结题
起止时间:
1994-08-01 至 2004-04-30
中文摘要
结肠癌是癌症死亡的第二大原因,
而小肠癌是一种相对较常见的癌症,
罕见事件。肠道肿瘤是由一系列的体细胞突变发展而来的
在起始事件如DNA-烷基化或氧化之后。我们
主要假设是小肠(SI)和大肠(LI)
对这两种重要形式的DNA损伤(烷基化和
氧化),这是肿瘤发病率差异的关键原因,
这两个网站。我们的第二个假设是SI细胞受到保护,
肿瘤诱导,因为它们产生较少的活性氧(ROS),
对DNA和LI细胞的氧化损伤更少。在具体目标#1中,我们将注入
用DNA烷化剂氧化偶氮甲烷处理大鼠并测量体内DNA损伤,
在注射后48小时内SI和LI中的修复和凋亡。DNA
损伤和修复通过定量免疫组织化学测定,
O 6-甲基鸟嘌呤加合物及其修复酶;
TUNEL检测。在具体的目标#2中,我们将确定体内对
DNA氧化剂葡聚糖硫酸钠在大鼠SI和LI内的前48
h后除去氧化剂。DNA损伤是通过定量
8 oxodG加合物的免疫组织化学;特异性修复酶的活性
通过核酸内切酶测定8 oxodG;和通过TUNEL测定凋亡。在
具体目标#3我们将确定氧化DNA损伤的稳态水平
以及青年和老年大鼠SI和LI中ROS的产生,
SI和LI的产生是由于线粒体电子
运输DNA损伤将通过FLARE测定来评估,ROS产生将通过
在与以下物质孵育的细胞中,活体染料2 ',7'-二氯荧光素的氧化
并且不含电子传递抑制剂。
英文摘要
Colon cancer is the second leading cause of death from cancer in
the United States today whereas cancer of the small intestine is a relatively
rare event. Intestinal tumors develop from a series of somatic mutations
subsequent to an initiating event such as DNA-alkylation or oxidation. Our
primary hypothesis is that the small intestine (SI) and large intestine (LI)
respond differently to these two important forms of DNA damage (alkylation and
oxidation), which is a key reason for the difference in tumor incidence at
these two sites. Our secondary hypothesis is that SI cells are protected from
tumor induction because they produce less reactive oxygen species (ROS) and
less oxidative damage to DNA and LI cells. In specific aim # 1 we will inject
rats with the DNA alkylating agent azoxymethane and measure in vivo DNA damage,
repair and apoptosis in SI and LI over the 48 h period post injection. DNA
damage and repair are measured by quantitative immunohistochemistry of
O6-methylguanine adducts and its repair enzyme; and apoptosis is detected by
the TUNEL assay. In specific aim #2 we will determine in vivo response to the
DNA oxidizing agent dextran sodium sulfate in rat SI and LI within the first 48
h after removal of the oxidizing agent. DNA damage is measured by quantitative
immunohistochemistry of 8oxodG adducts; activity of the repair enzyme specific
for 8oxodG by an endonuclease assay; and apoptosis by the TUNEL assay. In
specific aim #3 we will determine steady state levels of oxidative DNA damage
and ROS generation in SI and LI in young and old rats and whether or not ROS
generation in SI and LI is due to differences in mitochondrial electron
transport. DNA damage will be assessed by the FLARE assay and ROS production by
oxidation of the vital dye 2',7'-dichlorofluorescein in cells incubated with
and without electron transport inhibitors.
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科研奖励(0)
会议论文
DIET,APOPTOSIS AND COLON CARCINOGENESIS
-
批准号:6698029
-
项目类别:
-
资助金额:$32.74万
-
财政年份:2001
-
负责人:JOANNE R LUPTON
-
依托单位:
DIET,APOPTOSIS AND COLON CARCINOGENESIS
-
批准号:6497572
-
项目类别:
-
资助金额:$32.74万
-
财政年份:2001
-
负责人:JOANNE R LUPTON
-
依托单位:
DIET,APOPTOSIS AND COLON CARCINOGENESIS
-
批准号:6628210
-
项目类别:
-
资助金额:$32.74万
-
财政年份:2001
-
负责人:JOANNE R LUPTON
-
依托单位:
DIET,APOPTOSIS AND COLON CARCINOGENESIS
-
批准号:6266806
-
项目类别:
-
资助金额:$32.44万
-
财政年份:2001
-
负责人:JOANNE R LUPTON
-
依托单位:
CORE--NUTRITION
-
批准号:6438213
-
项目类别:
-
资助金额:$11.79万
-
财政年份:2001
-
负责人:JOANNE R LUPTON
-
依托单位:
CORE--NUTRITION
-
批准号:6347498
-
项目类别:
-
资助金额:$11.79万
-
财政年份:2000
-
负责人:JOANNE R LUPTON
-
依托单位:
CORE--NUTRITION
-
批准号:6301559
-
项目类别:
-
资助金额:$6.52万
-
财政年份:2000
-
负责人:JOANNE R LUPTON
-
依托单位:
CORE--NUTRITION
-
批准号:6106497
-
项目类别:
-
资助金额:$6.52万
-
财政年份:1999
-
负责人:JOANNE R LUPTON
-
依托单位:
CORE--NUTRITION
-
批准号:6271358
-
项目类别:
-
资助金额:$5.17万
-
财政年份:1998
-
负责人:JOANNE R LUPTON
-
依托单位:
RESPONSE TO DNA DAMAGE--COLON VS SMALL INTESTINE
-
批准号:6194306
-
项目类别:
-
资助金额:$22.6万
-
财政年份:1994
-
负责人:JOANNE R LUPTON
-
依托单位:
RESPONSE TO DNA DAMAGE--COLON VS SMALL INTESTINE
-
批准号:6376029
-
项目类别:
-
资助金额:$22.68万
-
财政年份:1994
-
负责人:JOANNE R LUPTON
-
依托单位:
FIBER, SHORT CHAIN FATTY ACIDS AND COLON CANCER
-
批准号:2429796
-
项目类别:
-
资助金额:$12.58万
-
财政年份:1994
-
负责人:JOANNE R LUPTON
-
依托单位:
FIBER, SHORT CHAIN FATTY ACIDS AND COLON CANCER
-
批准号:2102515
-
项目类别:
-
资助金额:$21.18万
-
财政年份:1994
-
负责人:JOANNE R LUPTON
-
依托单位:
FIBER, SHORT CHAIN FATTY ACIDS AND COLON CANCER
-
批准号:2712680
-
项目类别:
-
资助金额:$6.7万
-
财政年份:1994
-
负责人:JOANNE R LUPTON
-
依托单位:
FIBER, SHORT CHAIN FATTY ACIDS AND COLON CANCER
-
批准号:2102516
-
项目类别:
-
资助金额:$16.29万
-
财政年份:1994
-
负责人:JOANNE R LUPTON
-
依托单位:
RESPONSE TO DNA DAMAGE--COLON VS SMALL INTESTINE
-
批准号:6633182
-
项目类别:
-
资助金额:$22.68万
-
财政年份:1994
-
负责人:JOANNE R LUPTON
-
依托单位:
FIBER, SHORT CHAIN FATTY ACIDS AND COLON CANCER
-
批准号:2102514
-
项目类别:
-
资助金额:$15.45万
-
财政年份:1994
-
负责人:JOANNE R LUPTON
-
依托单位:
海外基金