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

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Swift, Lucy H
University of Lethbridge. Faculty of Arts and Science
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Lethbridge, Alta : University of Lethbridge, Dept. of Biological Sciences
We 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.
apoptosis , checkpoint adaptation , cisplatin , genotoxic agents , mitosis