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Int. J. Mol. Sci. 2017, 18(2), 360; doi:10.3390/ijms18020360

Multinucleated Giant Cancer Cells Produced in Response to Ionizing Radiation Retain Viability and Replicate Their Genome

Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, AB T6G 1Z2, Canada
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Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 29 December 2016 / Revised: 29 January 2017 / Accepted: 3 February 2017 / Published: 8 February 2017
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Abstract

Loss of wild-type p53 function is widely accepted to be permissive for the development of multinucleated giant cells. However, whether therapy-induced multinucleation is associated with cancer cell death or survival remains controversial. Herein, we demonstrate that exposure of p53-deficient or p21WAF1 (p21)-deficient solid tumor-derived cell lines to ionizing radiation (between 2 and 8 Gy) results in the development of multinucleated giant cells that remain adherent to the culture dish for long times post-irradiation. Somewhat surprisingly, single-cell observations revealed that virtually all multinucleated giant cells that remain adherent for the duration of the experiments (up to three weeks post-irradiation) retain viability and metabolize 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT), and the majority (>60%) exhibit DNA synthesis. We further report that treatment of multinucleated giant cells with pharmacological activators of apoptosis (e.g., sodium salicylate) triggers their demise. Our observations reinforce the notion that radiation-induced multinucleation may reflect a survival mechanism for p53/p21-deficient cancer cells. With respect to evaluating radiosensitivity, our observations underscore the importance of single-cell experimental approaches (e.g., single-cell MTT) as the creation of viable multinucleated giant cells complicates the interpretation of the experimental data obtained by commonly-used multi-well plate colorimetric assays. View Full-Text
Keywords: ionizing radiation; p53; p21WAF1; multinucleated giant cells; premature senescence; viability; proliferation; colony forming ability; 96-well plate XTT; single-cell MTT ionizing radiation; p53; p21WAF1; multinucleated giant cells; premature senescence; viability; proliferation; colony forming ability; 96-well plate XTT; single-cell MTT
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mirzayans, R.; Andrais, B.; Scott, A.; Wang, Y.W.; Kumar, P.; Murray, D. Multinucleated Giant Cancer Cells Produced in Response to Ionizing Radiation Retain Viability and Replicate Their Genome. Int. J. Mol. Sci. 2017, 18, 360.

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