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Prediction of radiosensitivity in human bladder cell lines using nuclear chromatin phenotype
Author(s) -
Rajab Nor F.,
McKenna Declan J.,
Diamond Jim,
Williamson Kate,
Hamilton Peter W.,
McKelveyMartin Valerie J.
Publication year - 2006
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.20329
Subject(s) - chromatin , radioresistance , radiosensitivity , comet assay , cell culture , biology , microbiology and biotechnology , phenotype , dna damage , genetics , dna , medicine , radiation therapy , gene
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 γ‐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. © 2006 International Society for Analytical Cytology