RESPONSE TO DNA DAMAGE--COLON VS SMALL INTESTINE
RESPONSE TO DNA DAMAGE--COLON VS SMALL INTESTINE
批准号:
6633182
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 2005-04-30
中文摘要
结肠癌是#年癌症死亡的第二大原因。
今天的美国,而小肠癌是一种相对
罕见的事件。肠道肿瘤由一系列体细胞突变发展而来
在诸如DNA烷基化或氧化之类的启动事件之后。我们的
基本假设是小肠(SI)和大肠(LI)
对这两种重要的DNA损伤形式(烷基化和
氧化),这是肿瘤发病率不同的关键原因
这两个地点。我们的第二个假设是SI细胞受到保护
诱导肿瘤,因为它们产生较少的活性氧簇(ROS)和
减少对DNA和LI细胞的氧化损伤。在具体目标#1中,我们将注入
用DNA烷化剂偶氮甲烷和测量体内DNA损伤的大鼠,
注射后48h内SI和LI的修复和细胞凋亡。脱氧核糖核酸
损伤和修复通过定量免疫组织化学方法测量
O6-甲基鸟嘌呤加合物及其修复酶;
末端标记法。在特定的目标#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中的前48
H后去除氧化剂。DNA损伤是通过定量的
8oxodG加合物的免疫组织化学;特异性修复酶的活性
用核酸内切酶法检测8oxodG的表达,用TUNEL法检测细胞凋亡率。在……里面
具体目标#3我们将确定DNA氧化损伤的稳定水平
幼年和老年大鼠SI和LI中ROS的产生以及是否存在ROS
SI和LI的产生是由于线粒体电子的差异
运输。DNA损伤将通过耀斑试验和ROS产生进行评估
活性染料2‘,7’-二氯荧光素在细胞中的氧化
而且没有电子传递抑制剂。
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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DOI:
10.1093/jn/134.3.489
发表时间:
2004-03
期刊:
The Journal of nutrition
影响因子:
--
作者:
[Guoyao Wu;Yun-Zhong Fang;Sheng Yang;J. Lupton;N. Turner]
通讯作者:
Guoyao Wu;Yun-Zhong Fang;Sheng Yang;J. Lupton;N. Turner
Diet and carcinogen alter luminal butyrate concentration and intracellular pH in isolated rat colonocytes.
饮食和致癌物质改变离体大鼠结肠细胞中的管腔丁酸盐浓度和细胞内 pH 值。
DOI:
10.1080/01635589709514530
发表时间:
1997
期刊:
Nutrition and cancer
影响因子:
--
作者:
[Zoran,DL, Barhoumi,R, Burghardt,RC, Chapkin,RS, Lupton,JR]
通讯作者:
Lupton,JR
DOI:
10.1097/00008469-199510000-00007
发表时间:
1995-10
期刊:
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation
影响因子:
--
作者:
[J. Lupton]
通讯作者:
J. Lupton
DOI:
10.1080/01635589409514352
发表时间:
1994
期刊:
Nutrition and cancer
影响因子:
--
作者:
[J. Zhang;J. Lupton]
通讯作者:
J. Zhang;J. Lupton
DOI:
10.1093/jn/128.8.1262
发表时间:
1998-08
期刊:
The Journal of nutrition
影响因子:
--
作者:
[J. Zhang;G. Wu;R. Chapkin;J. Lupton]
通讯作者:
J. Zhang;G. Wu;R. Chapkin;J. Lupton
共 6 条
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:6512984
-
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:
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:
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