International Journal of Molecular Sciences | |
Impact of Premature Senescence on Radiosensitivity Measured by High Throughput Cell-Based Assays | |
David Murray1  Razmik Mirzayans1  Bonnie Andrais1  | |
[1] Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada; | |
关键词: ionizing radiation; p53 signaling; premature senescence; viability; proliferation; apoptosis; colony forming ability; MTT; XTT; CellTiter-Blue; | |
DOI : 10.3390/ijms18071460 | |
来源: DOAJ |
【 摘 要 】
In 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.
【 授权许可】
Unknown