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Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
* Author to whom correspondence should be addressed.
Received: 16 September 2013; in revised form: 29 October 2013 / Accepted: 4 November 2013 / Published: 13 November 2013
Abstract: Ionizing radiation triggers diverse responses in human cells encompassing apoptosis, necrosis, stress-induced premature senescence (SIPS), autophagy, and endopolyploidy (e.g., multinucleation). Most of these responses result in loss of colony-forming ability in the clonogenic survival assay. However, not all modes of so-called clonogenic cell “death” are necessarily advantageous for therapeutic outcome in cancer radiotherapy. For example, the crosstalk between SIPS and autophagy is considered to influence the capacity of the tumor cells to maintain a prolonged state of growth inhibition that unfortunately can be succeeded by tumor regrowth and disease recurrence. Likewise, endopolyploid giant cells are able to segregate into near diploid descendants that continue mitotic activities. Herein we review the current knowledge on the roles that the p53 and p21WAF1 tumor suppressors play in determining the fate of human fibroblasts (normal and Li-Fraumeni syndrome) and solid tumor-derived cells after exposure to ionizing radiation. In addition, we discuss the important role of WIP1, a p53-regulated oncogene, in the temporal regulation of the DNA damage response and its contribution to p53 dynamics post-irradiation. This article highlights the complexity of the DNA damage response and provides an impetus for rethinking the nature of cancer cell resistance to therapeutic agents.
Keywords: ionizing radiation; p53; WIP1; premature senescence; apoptosis; endopolyploidy
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Mirzayans, R.; Andrais, B.; Scott, A.; Wang, Y.W.; Murray, D. Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status. Int. J. Mol. Sci. 2013, 14, 22409-22435.
Mirzayans R, Andrais B, Scott A, Wang YW, Murray D. Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status. International Journal of Molecular Sciences. 2013; 14(11):22409-22435.
Mirzayans, Razmik; Andrais, Bonnie; Scott, April; Wang, Ying W.; Murray, David. 2013. "Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status." Int. J. Mol. Sci. 14, no. 11: 22409-22435.