1. A HYPOTHESIS OF RADIORESISTANCE AND CELL-SURVIVAL CURVE SHAPE BASED ON CELL-CYCLE PROGRESSION AND DAMAGE TOLERANCE
- Author
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Carsten Herskind, Junqi Liu, Hui Hui Ma, Elsa Angelie, Frederik Wenz, Frank A. Giordano, L. Ma, Xiaolei Liu, Yingying Zhang, Marlon R. Veldwijk, and Qi Liu
- Subjects
Cell Survival ,Cell ,Apoptosis ,Human skin ,Biology ,Radiation Tolerance ,Cell Line ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Radioresistance ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lymphocytes ,Survival analysis ,Radiation ,Radiological and Ultrasound Technology ,X-Rays ,Lymphoblast ,Public Health, Environmental and Occupational Health ,Dose-Response Relationship, Radiation ,Cell Cycle Checkpoints ,General Medicine ,Fibroblasts ,Dose–response relationship ,medicine.anatomical_structure ,Cell culture ,030220 oncology & carcinogenesis ,Cancer research ,Glioblastoma ,Cell survival curve - Abstract
Exponential survival curves of early-passage human fibroblasts challenge classic biophysical models of cell inactivation. Thus, X-ray doses of 2-4 Gy inactivate normal, human skin fibroblasts in spite of negligible residual double-strand breaks. By contrast, radioresistant p53-mutant U251 glioblastoma cells proliferate in spite of residual damage. Similarly, p53 wildtype TK6 lymphoblastoid cells show exponential survival curves while the related p53-mutant WTK1 cell line continued to proliferate and showed a shouldered survival curve. Here, we propose a model in which the radioresistant shoulder region is due to tolerance to certain types or amounts of residual damage that would otherwise inactivate normal cells. Thus, the steeper initial slope and absence of a shoulder in the survival curve of normal cells may not imply a higher number of residual lesions but rather non-tolerance to these lesions.
- Published
- 2018
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