Testing the relationship between checkpoint adaptation and micronuclei in human fibroblastic glioma and normal lung cells

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dc.contributor.authorLewis, Cody W.
dc.contributor.supervisorGolsteyn, Roy
dc.date.accessioned2014-10-03T20:13:08Z
dc.date.available2014-10-03T20:13:08Z
dc.date.issued2014-10-03
dc.degree.levelMastersen_US
dc.description.abstractThis thesis examines the relationship between checkpoint adaptation and micronuclei in human cancer cells with damaged DNA. When cancer cells are exposed to genotoxic agents they can form micronuclei, although the precise process has yet to be described. I examined glioma cells (M059K) and found that 48% of the cells contain micronuclei after treatment with cisplatin. Treated cells also underwent checkpoint adaptation: they signalled damaged DNA, had active Chk1, arrested in G2-phase, and then entered mitosis. The relationship between checkpoint adaptation and micronuclei was confirmed by use of chemical inhibitors against Chk1 or Cdk1, which have key roles in checkpoint adaptation. When Chk1 was inhibited in treated cells, additional micronuclei formed, whereas if Cdk1 was inhibited, no additional micronuclei formed. I treated normal cells (WI-38) with cisplatin and found that they did not undergo checkpoint adaptation or form micronuclei. These data demonstrate that micronuclei are an outcome of checkpoint adaptation.en_US
dc.description.sponsorshipAlberta Innovates Technology Futures, Alberta Scholarship Programs, University of Lethbridge School of Graduate Studiesen_US
dc.identifier.urihttps://hdl.handle.net/10133/3505
dc.language.isoen_CAen_US
dc.proquest.subject0379en_US
dc.proquest.subject0992
dc.proquest.subject0419
dc.proquestyesYesen_US
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences.
dc.publisher.departmentBiological Sciencesen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)
dc.subjectcancer cells
dc.subjectcheckpoint adaptation
dc.subjectgenotoxic agents
dc.subjectglioma cells
dc.subjectmicronuclei
dc.subjectnormal cells
dc.titleTesting the relationship between checkpoint adaptation and micronuclei in human fibroblastic glioma and normal lung cellsen_US
dc.typeThesisen_US
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