Impact of Premature Senescence on Radiosensitivity Measured by High Throughput Cell-Based Assays
AbstractIn most p53 wild-type human cell types, radiosensitivity evaluated by the colony formation assay predominantly reflects stress-induced premature senescence (SIPS) and not cell death (Int. J. Mol. Sci. 2017, 18, 928). SIPS is a growth-arrested state in which the cells acquire flattened and enlarged morphology, remain viable, secrete growth-promoting factors, and can give rise to tumor-repopulating progeny. The impact of SIPS on radiosensitivity measured by short-term assays remains largely unknown. We report that in four p53 wild-type human solid tumor-derived cell lines (HCT116, SKNSH, MCF7 and A172): (i) the conventional short-term growth inhibition assay (3 days post-irradiation) generates radiosensitivity data comparable to that measured by the laborious and time-consuming colony formation assay; (ii) radiation dose-response curves obtained by multiwell plate colorimetric/fluorimetric assays are markedly skewed towards radioresistance, presumably reflecting the emergence of highly enlarged, growth-arrested and viable cells; and (iii) radiation exposure (e.g., 8 Gy) does not trigger apoptosis or loss of viability over a period of 3 days post-irradiation. Irrespective of the cell-based assay employed, caution should be exercised to avoid misinterpreting radiosensitivity data in terms of loss of viability and, hence, cell death. View Full-Text
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Mirzayans, R.; Andrais, B.; Murray, D. Impact of Premature Senescence on Radiosensitivity Measured by High Throughput Cell-Based Assays. Int. J. Mol. Sci. 2017, 18, 1460.
Mirzayans R, Andrais B, Murray D. Impact of Premature Senescence on Radiosensitivity Measured by High Throughput Cell-Based Assays. International Journal of Molecular Sciences. 2017; 18(7):1460.Chicago/Turabian Style
Mirzayans, Razmik; Andrais, Bonnie; Murray, David. 2017. "Impact of Premature Senescence on Radiosensitivity Measured by High Throughput Cell-Based Assays." Int. J. Mol. Sci. 18, no. 7: 1460.
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