MODULATION OF DNA REPAIR BY P53 IN HUMAN UROEPITHELIUM
MODULATION OF DNA REPAIR BY P53 IN HUMAN UROEPITHELIUM
批准号:
2870290
负责人:
SANTHANAM SWAMINATHAN
金额:
$20.39万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-12-17 至 2001-11-30
关键词:
DNA damage DNA repair biphenylamines bladder neoplasm carcinogen testing chemical carcinogen chemical carcinogenesis enzyme activity human genetic material tag human tissue hypoxanthine phosphoribosyltransferase mutagen testing mutagens neoplasm /cancer genetics p53 gene /protein tissue /cell culture transitional cell carcinoma urinary bladder epithelium
中文摘要
野生型p53 (wt-p53)调节DNA修复的假说
英文摘要
The hypothesis that wild-type p53 (wt-p53) modulates repair of DNA
damage caused by the human bladder carcinogen, 4-aminobiphenyl (ABP),
will be tested in its actual in vivo target cell types, namely the human
uroepithelial cells (HUC). Using a unique set of isogeneic cell lines,
differing in wt-p53 functional status (due to the expression of HPV-E6
oncoprotein or a transdominant mutant of p53), the following questions
will be addressed.
What types of DNA damage (covalent adducts and strand breaks) are caused
by the N-hydroxy metabolites of ABP in HUC? Does the loss of function
of wt-p53 cause a reduction in the rate of DNA repair either at the
level of overall genomic DNA or at the level of an individual gene, such
as hypoxanthine guanine phosphoribosyl transferase (HGPRT) gene?; and
if so, does the effect of wt-p53 dependent upon the transcription
status?
To answer the above, DNA strand breaks and covalent adduct formation
will be analyzed by alkaline elution, sucrose gradient sedimentation and
by 32P-postlabeling methods. The effect of loss of function of wt-p53
on DNA lesion will be determined by comparison of the kinetics of DNA
repair between the set of isogeneic cell lines, differing in wt-p53
activity. The kinetics of DNA repair will be measured by: 1) monitoring
the disappearance of ABP-DNA adducts by 32P-postlabeling; 2) by
quantifying the unrepaired DNA adducts by digestion with E. Coli UvrABC
nuclease; and 3) by estimating the DNA repair patch synthesis. The
effect of wt-p53 on the transcription dependent versus -independent
repair will be determined by measuring the kinetics of repair synthesis
using riboprobes selective for the transcribed versus nontranscribed
strand of HGPRT.
A rare feature of our HUC system is that it permits us to test the
effect of the environmental carcinogen ABP, directly on its in vivo
target cells, and thus surmount the serious limitations of the
fibroblast or rodent culture system. The results of these studies have
important etiologic, mechanistic and therapeutic implications in human
cancers.
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ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
-
批准号:6309199
-
项目类别:
-
资助金额:$0.75万
-
财政年份:2000
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
CORE--SCIENTIFIC INSTRUMENT FACILITY
-
批准号:6316509
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项目类别:
-
资助金额:$28.96万
-
财政年份:2000
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
CORE--GLASSWARE AND STERILIZATION
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批准号:6316508
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项目类别:
-
资助金额:$28.96万
-
财政年份:2000
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
CORE--GLASSWARE AND STERILIZATION
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批准号:6101621
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项目类别:
-
资助金额:$28.96万
-
财政年份:1999
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
CORE--SCIENTIFIC INSTRUMENT FACILITY
-
批准号:6101622
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项目类别:
-
资助金额:$28.96万
-
财政年份:1999
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
-
批准号:6298196
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项目类别:
-
资助金额:$0.75万
-
财政年份:1999
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
CORE--GLASSWARE AND STERILIZATION
-
批准号:6217225
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项目类别:
-
资助金额:$28.96万
-
财政年份:1999
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
CORE--SCIENTIFIC INSTRUMENT FACILITY
-
批准号:6217226
-
项目类别:
-
资助金额:$28.96万
-
财政年份:1999
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
CORE--GLASSWARE AND STERILIZATION
-
批准号:6268762
-
项目类别:
-
资助金额:$27.95万
-
财政年份:1998
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
CORE--SCIENTIFIC INSTRUMENT FACILITY
-
批准号:6268763
-
项目类别:
-
资助金额:$27.95万
-
财政年份:1998
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
MODULATION OF DNA REPAIR BY P53 IN HUMAN UROEPITHELIUM
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批准号:6124697
-
项目类别:
-
资助金额:$21.78万
-
财政年份:1998
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
-
批准号:6281630
-
项目类别:
-
资助金额:$0.04万
-
财政年份:1998
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
MODULATION OF DNA REPAIR BY P53 IN HUMAN UROEPITHELIUM
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批准号:6329089
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项目类别:
-
资助金额:$22.44万
-
财政年份:1998
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
-
批准号:6252131
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项目类别:
-
资助金额:$0.52万
-
财政年份:1997
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
-
批准号:3250850
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项目类别:
-
资助金额:$7.94万
-
财政年份:1984
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
ACTIVATION OF CARCINOGENS BY HUMAN UROTHELIUM IN VITRO
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批准号:3250847
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项目类别:
-
资助金额:$15.21万
-
财政年份:1984
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
-
批准号:3250854
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项目类别:
-
资助金额:$15.14万
-
财政年份:1984
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
-
批准号:3250852
-
项目类别:
-
资助金额:$14.33万
-
财政年份:1984
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
-
批准号:3250853
-
项目类别:
-
资助金额:$14.67万
-
财政年份:1984
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
-
批准号:2153333
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项目类别:
-
资助金额:$15.67万
-
财政年份:1984
-
负责人:SANTHANAM SWAMINATHAN
-
依托单位:
海外基金