Bile acid-induced DNA damage and repair in bacterial and mammalian cells.

Persistent Link:
http://hdl.handle.net/10150/184976
Title:
Bile acid-induced DNA damage and repair in bacterial and mammalian cells.
Author:
Kandell, Risa Lynne.
Issue Date:
1990
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:
Colon cancer is the second most common type of cancer in the United States. Its incidence is linked epidemiologically to high levels of bile acids in the feces. Bile acids have been implicated as promoters and cocarcinogens in the etiology of colon cancer and as comutagens and mutagens in bacteria. These observations suggest the hypothesis that bile acids may damage DNA. By using the DNA-damage inducible SOS system in Escherichia coli, this study shows that when bacteria are exposed to bile acids there is induction of the SOS repair system and preferential survival of cells undergoing repair. Additionally, differential killing assays using repair defective bacteria show strains defective in recombinational repair or excision repair have lower survival when treated with bile acids than their parental wild-type counterparts. Human fibroblasts were treated with bile acids and unscheduled DNA synthesis (UDS) was measured. UDS is considered to represent the DNA synthesis step in excision repair. UDS, measured by autoradiography, was found to significantly increase in human fibroblasts upon treatment with bile acids. In addition, differential cytotoxicity assays with Chinese Hamster Ovary cells showed that different DNA-repair pathway defective cells were sensitive to different bile acids. Introduction of DNA damage and induction of DNA-repair by bile acids implicates them as possible direct carcinogens in the etiology of colon cancer.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Bile acids; DNA damage; DNA repair; Biochemical genetics; Carcinogenesis
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Genetics; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Bernstein, Harris

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleBile acid-induced DNA damage and repair in bacterial and mammalian cells.en_US
dc.creatorKandell, Risa Lynne.en_US
dc.contributor.authorKandell, Risa Lynne.en_US
dc.date.issued1990en_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.abstractColon cancer is the second most common type of cancer in the United States. Its incidence is linked epidemiologically to high levels of bile acids in the feces. Bile acids have been implicated as promoters and cocarcinogens in the etiology of colon cancer and as comutagens and mutagens in bacteria. These observations suggest the hypothesis that bile acids may damage DNA. By using the DNA-damage inducible SOS system in Escherichia coli, this study shows that when bacteria are exposed to bile acids there is induction of the SOS repair system and preferential survival of cells undergoing repair. Additionally, differential killing assays using repair defective bacteria show strains defective in recombinational repair or excision repair have lower survival when treated with bile acids than their parental wild-type counterparts. Human fibroblasts were treated with bile acids and unscheduled DNA synthesis (UDS) was measured. UDS is considered to represent the DNA synthesis step in excision repair. UDS, measured by autoradiography, was found to significantly increase in human fibroblasts upon treatment with bile acids. In addition, differential cytotoxicity assays with Chinese Hamster Ovary cells showed that different DNA-repair pathway defective cells were sensitive to different bile acids. Introduction of DNA damage and induction of DNA-repair by bile acids implicates them as possible direct carcinogens in the etiology of colon cancer.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBile acidsen_US
dc.subjectDNA damageen_US
dc.subjectDNA repairen_US
dc.subjectBiochemical geneticsen_US
dc.subjectCarcinogenesisen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGeneticsen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBernstein, Harrisen_US
dc.contributor.committeememberDenise, Sueen_US
dc.contributor.committeememberMcCoy, Tomen_US
dc.contributor.committeememberRay, Dennisen_US
dc.contributor.committeememberWard, Oscaren_US
dc.identifier.proquest9022113en_US
dc.identifier.oclc703638474en_US
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