MECHANISMS OF PROTECTION AGAINST CANCER BY INDUCTION OF PHASE 2 ENZYMES
MECHANISMS OF PROTECTION AGAINST CANCER BY INDUCTION OF PHASE 2 ENZYMES
批准号:
6102351
负责人:
PAUL TALALAY
金额:
$22.09万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1999
资助国家:
美国
项目状态:
已结题
起止时间:
1999-01-01 至 1999-12-31
关键词:
Cruciferae NAD(P)H dehydrogenase affinity chromatography aflatoxins antioxidants benzanthracenes carcinogen testing carcinogenesis inhibitor chemical carcinogenesis cytochrome P450 enzyme induction /repression enzyme inhibitors gel mobility shift assay genetic enhancer element isothiocyanates laboratory rat mass spectrometry nuclear magnetic resonance spectroscopy nutrition related tag plant extracts recombinant proteins transcription factor
中文摘要
该项目的总体目标是通过以下方式降低癌症风险
降低对致癌物的毒性和肿瘤效应的敏感性。
这个项目利用了许多化学物质
(一些存在于可食用植物中)防癌,也是诱导期
2解毒酶,如谷胱甘肽转移酶(GST)和NAD(P)H:
(对苯二酚受体)氧化还原酶(对苯二酚还原酶;OR),并升高
组织谷胱甘肽水平。这种细胞反应增强了
处理致癌物质。化学保护酶诱导剂有很多种
结构类型,要么是单功能(提升阶段2酶
选择性地),或双功能(提高两个相1酶[细胞色素P-
450]和动物细胞和组织中的第二相酶[例如QR、GST]。
几乎所有的单功能诱导剂都是亲电的。在AIM 1.1中,诱导剂-
在高密度条件下,实验室将培育出丰富的可食用植物。
标准化的条件,它们的诱导剂的化学成分将是
特色化的。由于异硫氰酸酯类萝卜硫醚[1-异硫氰酸酯-4-
(甲基亚硫基)丁烷]是一些
各种十字花科植物(西兰花),并阻止乳腺癌的形成
大鼠,一个重大的新方向就是研究其作用机制。
异硫氰酸酯的抗癌作用(目标1.2)。什么是
2相酶诱导与1相酶的相对重要性
抑制癌变,以及GSTs在肿瘤发生中的作用
异硫氰酸酯代谢。在DMBA中,AIM 1.3旨在评估
萝卜硫素对大鼠乳腺肿瘤模型的抗癌作用
和合成类似物,高诱导性植物和其他相2酶
将被分离或合成的诱导剂。目标1.4是确定
与诱导剂反应的初级细胞信号蛋白(S),并
阐明2相酶调控的分子机制
诱导者。拟议的分子、细胞、植物和动物研究将
确定新的化学保护剂,阐明其作用机制,并评估
它们在动物身上的功效。他们还将提供可食用的制剂
项目建议的富含诱导剂和适合人体研究的植物
2.
英文摘要
The overall goals of this project are to lower the risk of cancer by
reducing susceptibility to the toxic and neoplastic effects of carcinogens.
This project exploits the well-established observation that many chemicals
(some present in edible plants) protect against cancer an also induce Phase
2 detoxication enzymes such as glutathione transferases (GST) and NAD(P)H:
(quinone acceptor) oxidoreductase (quinone reductase; OR), and elevate
tissue glutathione levels. This cellular response boosts the capacity to
dispose of carcinogens. Chemoprotective enzyme inducers are of many
structural types, an are either monofunctional (elevate Phase 2 enzymes
selectively), or bifunctional (elevate both Phase 1 enzymes [cytochromes P-
450] and Phase 2 enzymes [e.g., QR,GST] in animal cells and tissues.
Nearly all monofunctional inducers are electrophilic. In Aim 1.1 inducer-
rich edible plants will be produced in the laboratory under highly
standardized conditions, and the chemistry of their inducers will be
characterized. Since the isothiocyanate sulforaphane [1-isothiocyanato-4-
(methylsulfinyl)butane] is the principal monofunctional inducer of some
varieties of crucifers (broccoli), and blocks mammary tumor formation in
rats, a major new direction is the study of the mechanism of the
anticarcinogenic actions of isothiocyanates (Aim 1.2). What is the
relative importance of Phase 2 enzyme induction and Phase 1 enzyme
inhibition in blocking carcinogenesis, and what is the role of GSTs in
isothiocyanate metabolism. Aim 1.3 is designed to evaluate, in the DMBA
rat mammary tumor model, the anticarcinogenic properties of sulforaphane
and synthetic analogs, of high inducer plants, and of other Phase 2 enzyme
inducers that will be isolated or synthesized. Aim 1.4 is to identify the
primary cellular signaling protein(s) that react with the inducers, and to
elucidate the molecular mechanisms of the regulation of Phase 2 enzymes by
inducers. The proposed molecular, cellular, plant and animal studies will
identify new chemoprotectors, throw light on their mechanisms, and assess
their efficacy in animals. They will also provide preparations of edible
plants rich in inducers and suitable for human studies proposed in Project
No. 2.
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MORINGA LEAF OR SEED EXTRACT
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批准号:7604638
-
项目类别:
-
资助金额:$0.05万
-
财政年份:2006
-
负责人:PAUL TALALAY
-
依托单位:
Isolation & Evaluation of Anticarcinogenic Glucosinolate
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批准号:6765176
-
项目类别:
-
资助金额:$36.38万
-
财政年份:2002
-
负责人:PAUL TALALAY
-
依托单位:
Isolation and Evaluation of Anticarcinogenic Glucosinolates
-
批准号:7523682
-
项目类别:
-
资助金额:$35.0万
-
财政年份:2002
-
负责人:PAUL TALALAY
-
依托单位:
Isolation and Evaluation of Anticarcinogenic Glucosinolates
-
批准号:8114211
-
项目类别:
-
资助金额:$35.43万
-
财政年份:2002
-
负责人:PAUL TALALAY
-
依托单位:
Isolation and Evaluation of Anticarcinogenic Glucosinolates
-
批准号:7898648
-
项目类别:
-
资助金额:$36.77万
-
财政年份:2002
-
负责人:PAUL TALALAY
-
依托单位:
Isolation & Evaluation of Anticarcinogenic Glucosinolate
-
批准号:6895837
-
项目类别:
-
资助金额:$36.38万
-
财政年份:2002
-
负责人:PAUL TALALAY
-
依托单位:
Isolation & Evaluation of Anticarcinogenic Glucosinolate
-
批准号:6640295
-
项目类别:
-
资助金额:$36.38万
-
财政年份:2002
-
负责人:PAUL TALALAY
-
依托单位:
Isolation and Evaluation of Anticarcinogenic Glucosinolates
-
批准号:7676011
-
项目类别:
-
资助金额:$36.05万
-
财政年份:2002
-
负责人:PAUL TALALAY
-
依托单位:
Isolation & Evaluation of Anticarcinogenic Glucosinolate
-
批准号:6544639
-
项目类别:
-
资助金额:$36.38万
-
财政年份:2002
-
负责人:PAUL TALALAY
-
依托单位:
MECHANISMS OF PROTECTION AGAINST CANCER BY INDUCTION OF PHASE 2 ENZYMES
-
批准号:6300285
-
项目类别:
-
资助金额:$22.09万
-
财政年份:2000
-
负责人:PAUL TALALAY
-
依托单位:
MECHANISMS OF PROTECTION AGAINST CANCER BY INDUCTION OF PHASE 2 ENZYMES
-
批准号:6269275
-
项目类别:
-
资助金额:$21.82万
-
财政年份:1998
-
负责人:PAUL TALALAY
-
依托单位:
INTRA SUBJECT VARIABILITY IN METABOLISM OF GLUCOSINOLATES
-
批准号:6114404
-
项目类别:
-
资助金额:$2.06万
-
财政年份:1998
-
负责人:PAUL TALALAY
-
依托单位:
INTRASUBJECT VARIABILITY IN METABOLISM OF GLUCOSINOLATES (HS33A)
-
批准号:6114369
-
项目类别:
-
资助金额:$2.06万
-
财政年份:1998
-
负责人:PAUL TALALAY
-
依托单位:
COVERSION OF GLUCOSINOLATES TO ISOTHIOCYNATES IN VOLUNTEERS FED BROCCOLI
-
批准号:6114425
-
项目类别:
-
资助金额:$2.06万
-
财政年份:1998
-
负责人:PAUL TALALAY
-
依托单位:
EXCRETION OF URINARY DITHIOCARBAMATES IN HEALTHY VOLUNTEERS
-
批准号:6114356
-
项目类别:
-
资助金额:$2.06万
-
财政年份:1998
-
负责人:PAUL TALALAY
-
依托单位:
BOWEL FLORA ROLE IN CONVERSION OF GLUCOSINOLATES TO ISOTHIOCYANATES
-
批准号:6114365
-
项目类别:
-
资助金额:$2.06万
-
财政年份:1998
-
负责人:PAUL TALALAY
-
依托单位:
CONVERSION OF GLUCOSINOLATES TO ISOTHIOCYNATES IN SUBJECTS FED BROCCOLI SPROUTS
-
批准号:6114371
-
项目类别:
-
资助金额:$2.06万
-
财政年份:1998
-
负责人:PAUL TALALAY
-
依托单位:
GLUCOSINOLATE--ISOTHIOCYNATE CONVERSION AFTER EATING BROCCLI SPROUT HOMOGENATE
-
批准号:6114430
-
项目类别:
-
资助金额:$2.06万
-
财政年份:1998
-
负责人:PAUL TALALAY
-
依托单位:
CONVERSION OF GLUCOSINOLATES TO ISOTHIOCYANATES
-
批准号:6245417
-
项目类别:
-
资助金额:$2.23万
-
财政年份:1997
-
负责人:PAUL TALALAY
-
依托单位:
CONVERSION OF GLUCOSINOLATES TO ISOTHIOCYNATES IN SUBJECTS FED BROCCOLI SPROUTS
-
批准号:6275606
-
项目类别:
-
资助金额:$2.01万
-
财政年份:1997
-
负责人:PAUL TALALAY
-
依托单位:
海外基金