Analysis of colon cancer cells that survive checkpoint adaptation after treatment with a genotoxic age

dc.contributor.authorRahman, Tanzila
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorGolsteyn, Roy
dc.date.accessioned2014-10-28T02:44:10Z
dc.date.available2014-10-28T02:44:10Z
dc.date.issued2013
dc.degree.levelMasters
dc.descriptionx, 93 leaves : ill. ; 29 cmen_US
dc.description.abstractMost cancer treatments are genotoxic agents that target and damage DNA as part of their mechanism of action. Recently, it was discovered that cancer cells with damaged DNA can escape the DNA damage checkpoint and enter into mitosis, a process known as checkpoint adaptation. I used the human colon carcinoma cell line (HT-29) as a model to examine checkpoint adaptation in cells treated with camptothecin (CPT), a topoisomerase I inhibitor that damages DNA. Survival and clonogenic assays revealed that approximately between 1-3% of the cells that undergo checkpoint adaptation are able to survive CPT treatment. Immunofluorescence microscopy disclosed that approximately 90% of the surviving cells were negative for histone -H2AX, whereas, in parallel, the alkaline comet assay revealed that 73% of the cells displayed comets. Karyotype analysis showed survival cells had 35 chromosomes on average, whereas non-treated cells contained 65. FISH analysis revealed that survival cells appear to have major changes in chromosome structure because 45% of the chromosomes were missing telomeres and 28% of the telomeres were located in positions other than the tips of chromosomes. These findings provide valuable information about the integrity of the genome of cancer cells that survive checkpoint adaptation.en_US
dc.identifier.urihttps://hdl.handle.net/10133/3565
dc.language.isoen_CAen_US
dc.proquest.subject0992
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, c2013en_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectColon (Anatomy) -- Canceren_US
dc.subjectColon (Anatomy) -- Cancer -- Cytopathologyen_US
dc.subjectColon (Anatomy) -- Cancer -- Chemotherapyen_US
dc.subjectColon (Anatomy) -- Cancer -- Molecular aspectsen_US
dc.subjectDissertations, Academicen_US
dc.titleAnalysis of colon cancer cells that survive checkpoint adaptation after treatment with a genotoxic ageen_US
dc.typeThesisen_US
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