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A hypothesis of radioresistance and cell-survival curve shape based on cell-cycle progression and damage tolerance

Exponential survival curves of early-passage humanfibroblasts challenge classic biophysical models of cell inactivation. Thus,X-ray doses of 2–4 Gy inactivate normal, human skinfibroblasts in spite of negligible residual double-strand breaks. By con-trast, radioresistant p53-mutant U251 glioblastoma...

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Bibliographic Details
Main Authors: Herskind, Carsten (Author) , Liu, Qi (Author) , Liu, Xiaolei (Author) , Zhang, Yingying (Author) , Ma, Lin (Author) , Angelie, Elsa (Author) , Ma, Hui Hui (Author) , Liu, Junqi (Author) , Giordano, Frank Anton (Author) , Wenz, Frederik (Author) , Veldwijk, Marlon Romano (Author)
Format: Article (Journal)
Language:English
Published: 2019
In: Radiation protection dosimetry
Year: 2019, Volume: 183, Issue: 1/2, Pages: 107-110
ISSN:1742-3406
DOI:10.1093/rpd/ncy247
Online Access:Verlag, Volltext: https://doi.org/10.1093/rpd/ncy247
Verlag: https://academic.oup.com/rpd/article/183/1-2/107/5238184
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Author Notes:Carsten Herskind, Qi Liu, Xiaolei Liu, Yingying Zhang, Lin Ma, Elsa Angelie, Hui Hui Ma, Junqi Liu, Frank A. Giordano, Frederik Wenz and Marlon R. Veldwijk
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Summary:Exponential survival curves of early-passage humanfibroblasts challenge classic biophysical models of cell inactivation. Thus,X-ray doses of 2–4 Gy inactivate normal, human skinfibroblasts in spite of negligible residual double-strand breaks. By con-trast, radioresistant p53-mutant U251 glioblastoma cells proliferate in spite of residual damage. Similarly, p53 wildtype TK6lymphoblastoid cells show exponential survival curves while the related p53-mutant WTK1 cell line continued to proliferateand showed a shouldered survival curve. Here, we propose a model in which the radioresistant shoulder region is due to toler-ance to certain types or amounts of residual damage that would otherwise inactivate normal cells. Thus, the steeper initialslope and absence of a shoulder in the survival curve of normal cells may not imply a higher number of residual lesions butrather non-tolerance to these lesions.
Item Description:Advance Access publication 11 December 2018
Gesehen am 21.01.2020
Physical Description:Online Resource
ISSN:1742-3406
DOI:10.1093/rpd/ncy247

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