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12 March 2015 NFκB and Survivin-Mediated Radio-Adaptive Response
David J. Grdina, Jeffrey S. Murley, Richard C. Miller, Gayle E. Woloschak, Jian Jian Li
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A survivin-mediated radio-adaptive response was induced in SA-NH murine sarcoma cells following activation of nuclear transcription factor κB (NFκB) by very low doses of ionizing radiation of 5, 20 or 100 mGy. SA-NH cells and a clone stably transfected with a plasmid containing a mutated IκBα gene that prevents the activation of NFκB (SA-NH mIκBα1) were used to investigate the role of NFκB activation in the development and expression of the survivin-mediated radio-adaptive response. Tumor cells were exposed to very low doses of radiation 30 min prior to or at times ranging from 30 min to 6 h after the first of two 2 Gy doses separated by 24 h under in vitro conditions. Evidence of very low dose radiation induced a radio-adaptive response only in SA-NH but not SA-NH mIκBα1 cells was shown by both an increase in SA-NH cell survival of 20–40% using a standard colony forming assay and reduced apoptosis frequencies of 20–40% as determined by the TUNEL assay. Changes in survivin protein levels as a function of irradiation conditions were monitored by Western blot. A 100 mGy exposure 30 min prior to a 2 Gy dose resulted in an elevation in total survivin protein 24 h later in SA-NH but not SA-NH mIκBα1 cells. Transfection of cells with survivin siRNA inhibited elevation of survivin protein by very low dose radiation and the subsequent radio-adaptive response in SA-NH cells. These data suggest that the survivin-mediated radio-adaptive response is dependent upon the ability of cells to activate NFκB.

David J. Grdina, Jeffrey S. Murley, Richard C. Miller, Gayle E. Woloschak, and Jian Jian Li "NFκB and Survivin-Mediated Radio-Adaptive Response," Radiation Research 183(4), 391-397, (12 March 2015).
Received: 18 December 2014; Accepted: 1 January 2015; Published: 12 March 2015
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