Prediction of radiosensitivity in human bladder cell lines using nuclear chromatin phenotype.
BACKGROUND
Nuclear texture analysis measures phenotypic changes in chromatin distribution within a cell nucleus, while the alkaline Comet assay is a sensitive method for measuring the extent of DNA breakage in individual cells. The authors aim to use both methods to provide information about the sensitivity of cells to ionizing radiation.


METHODS
The alkaline Comet assay was performed on six human bladder carcinoma cell lines and one human urothelial cell line exposed to gamma-radiation doses from 0 to 10 Gy. Nuclear chromatin texture analysis of 40 features was then performed in the same cell lines exposed to 0, 2, and 6 Gy to explore if nuclear phenotype was related to radiation sensitivity.


RESULTS
Comet assay results demonstrated that the cell lines exhibited different levels of radiosensitivity and could be divided into a radiosensitive and a radioresistant group at >6 Gy. Using stepwise discriminant analysis, a subset of important nuclear texture features that best discriminated between sensitive and resistant cell lines were identified A classification function, defined using these features, correctly classified 81.75% of all cells into their radiosensitive or radioresistant groups based on their pretreatment chromatin phenotype. Posttreatment chromatin changes also varied between cell lines, with sensitive cell lines showing a relaxed chromatin conformation following radiation, whereas resistant cell lines exhibited chromatin condensation.


CONCLUSIONS
The authors conclude that the alkaline Comet assay and nuclear texture methodologies may prove to be valuable aids in predicting the response of tumor cells to radiotherapy.
Rajab
Nor F
NF
Cancer and Ageing Research Group, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, United Kingdom.
McKenna
Declan J
DJ
Diamond
Jim
J
Williamson
Kate
K
Hamilton
Peter W
PW
McKelvey-Martin
Valerie J
VJ
D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D002843:Chromatin / Q000378:metabolism; D020552:Comet Assay; D053960:DNA Breaks; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D006801:Humans; D011836:Radiation Tolerance; D001743:Urinary Bladder / Q000166:cytology / Q000528:radiation effects*; D019459:Urothelium / Q000166:cytology / Q000528:radiation effects
D002843:Chromatin