Abstract
We investigated the effect of an acidic environment on the radiation-induced G2/M arrest and apoptosis using RKO·C human colorectal cancer cells expressing wild-type p53 and RC10·1 cells, a subline of RKO·C cells deficient in p53 as well as p53+/+ MEFs and p53−/− MEFs (mouse embryonic fibroblasts). The cells were irradiated with 4 Gy or 12 Gy of γ-rays in pH 7.5 medium or pH 6.6 medium. p53 accentuated the progression of cells from radiation-induced G2/M arrest to apoptosis and the pH 6.6 environment suppressed the progression of cells through G2/M-phase to apoptosis after irradiation. Further analysis indicated that the radiation-induced G2/M arrest was due mainly to G2 arrest in both pH 7.5 and pH 6.6. Therefore, it was concluded that p53 enhances, and an acidic environment suppresses, the exit of cells from radiation-induced G2 arrest by altering cyclin B1-Cdc2 kinase activity. Cell Death and Differentiation (2000) 7, 729–738
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Abbreviations
- Cdc2 kinase:
-
cyclin-dependent serine/threonine protein kinase
- PARP:
-
poly(ADP-ribose) polymerase
- PI:
-
propidium iodide
- SDS–PAGE:
-
sodium dodecyl sulfate-poly acrylamide gel electrophoresis
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Acknowledgements
The authors are thankful to Dr. Seymour H Levitt for his continuous encouragement and Ms. Peggy T Stewart for her editorial assistance. This work was supported by a National Cancer Institute grant (CA13353) and KOSEF-1999-2-208-003-3.
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Park, H., Lyons, J., Ohtsubo, T. et al. Cell cycle progression and apoptosis after irradiation in an acidic environment. Cell Death Differ 7, 729–738 (2000). https://doi.org/10.1038/sj.cdd.4400702
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DOI: https://doi.org/10.1038/sj.cdd.4400702
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