Testing the relationship between checkpoint adaptation and micronuclei in human fibroblastic glioma and normal lung cells
Lewis, Cody W.
Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences.
This 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.
cancer cells , checkpoint adaptation , genotoxic agents , glioma cells , micronuclei , normal cells