Oxidative DNA damage and apoptosis induced by bile acid: Relevance to colon cancer

Persistent Link:
http://hdl.handle.net/10150/282863
Title:
Oxidative DNA damage and apoptosis induced by bile acid: Relevance to colon cancer
Author:
Boyer, Jean Zheng
Issue Date:
1998
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Bile acids have been linked to the etiology of colon cancer in various studies for over twenty-five years. However, the mechanism by which bile acids act in colon carcinogenesis is not known. By using an assay that can detect induction of the gadd153 stress response to DNA damage, I found that bile acids activate expression of gadd153 promoter. This observation implies that bile acids cause DNA damage. I then hypothesized that exposure of cells to bile acids produces reactive oxygen species which damage DNA. However, experiments to block gadd153 induction by bile acids using antioxidants, and to measure 8-OH-dG induced by bile acids were inconclusive. I also used p53 mutant cell lines to show that bile acid induction of apoptosis is p53-independent. In addition, my experiments showed that bile acid increased expression of gadd153 protein in HT-29 cells, and that gadd153 protein was constitutively overexpressed in HCT-116 cells with or without bile acid treatment. Thus, bile acid action in colon carcinogenesis may involve induction of DNA damage, induction of gadd153 as a protective stress response, and then if the damage is beyond repair, p53-independent apoptosis.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Genetics.; Biology, Cell.; Health Sciences, Oncology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Microbiology and Immunology
Degree Grantor:
University of Arizona
Advisor:
Bernstein, Harris

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleOxidative DNA damage and apoptosis induced by bile acid: Relevance to colon canceren_US
dc.creatorBoyer, Jean Zhengen_US
dc.contributor.authorBoyer, Jean Zhengen_US
dc.date.issued1998en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractBile acids have been linked to the etiology of colon cancer in various studies for over twenty-five years. However, the mechanism by which bile acids act in colon carcinogenesis is not known. By using an assay that can detect induction of the gadd153 stress response to DNA damage, I found that bile acids activate expression of gadd153 promoter. This observation implies that bile acids cause DNA damage. I then hypothesized that exposure of cells to bile acids produces reactive oxygen species which damage DNA. However, experiments to block gadd153 induction by bile acids using antioxidants, and to measure 8-OH-dG induced by bile acids were inconclusive. I also used p53 mutant cell lines to show that bile acid induction of apoptosis is p53-independent. In addition, my experiments showed that bile acid increased expression of gadd153 protein in HT-29 cells, and that gadd153 protein was constitutively overexpressed in HCT-116 cells with or without bile acid treatment. Thus, bile acid action in colon carcinogenesis may involve induction of DNA damage, induction of gadd153 as a protective stress response, and then if the damage is beyond repair, p53-independent apoptosis.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Genetics.en_US
dc.subjectBiology, Cell.en_US
dc.subjectHealth Sciences, Oncology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMicrobiology and Immunologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBernstein, Harrisen_US
dc.identifier.proquest9923177en_US
dc.identifier.bibrecord.b39471901en_US
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