Investigation of checkpoint adaptation in human cancer cells treated with the genotoxic agent cisplatin

dc.contributor.authorSwift, Lucy H
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorGolsteyn, Roy
dc.date.accessioned2015-11-30T18:45:55Z
dc.date.available2015-11-30T18:45:55Z
dc.date.issued2015
dc.degree.levelPh.Den_US
dc.description.abstractWe investigated checkpoint adaptation in HT-29 colorectal adenocarcinoma cells treated with cisplatin. Cells that undergo checkpoint adaptation arrest at and then abrogate the G2/M checkpoint to enter mitosis with damaged DNA. We identified that cytotoxic amounts of cisplatin induce either checkpoint adaptation or apoptosis in a concentration dependent manner. We also found that some cisplatin treated cells can survive checkpoint adaptation. These survival cells may contain rearranged genomes, because they entered mitosis with damaged DNA. Additionally, cisplatin treated cells can die when they are induced to undergo checkpoint adaptation but entry into mitosis is inhibited. This might prevent cells surviving treatment with rearranged genomes and could improve the efficacy of genotoxic anti-cancer drugs. Finally, we show that the response following checkpoint adaptation is not identical after treatment with two different genotoxic agents; both HT-29 and M059K glioma cells treated with camptothecin spend longer in mitosis than cells treated with cisplatin.en_US
dc.embargoNoen_US
dc.identifier.urihttps://hdl.handle.net/10133/3813
dc.language.isoen_CAen_US
dc.proquest.subject0379en_US
dc.proquest.subject0307en_US
dc.proquest.subject0992en_US
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta : University of Lethbridge, Dept. of Biological Sciencesen_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.subjectapoptosisen_US
dc.subjectcheckpoint adaptationen_US
dc.subjectcisplatinen_US
dc.subjectgenotoxic agentsen_US
dc.subjectmitosisen_US
dc.titleInvestigation of checkpoint adaptation in human cancer cells treated with the genotoxic agent cisplatinen_US
dc.typeThesisen_US
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