Gene expression profile changes correlating with radioresistance in human cell lines.
OBJECTIVE
To identify gene expression profiles specific to radioresistance of human cells.


METHODS
Global gene expression profiles of a total of 15 tumor and normal fibroblast cell lines were analyzed using DNA microarrays and statistical clustering methods. Initially, six of the cell lines were categorized into radioresistant (RG) or nonradioresistant (NRG) groups according to the radiation dose required to reduce their survival to 10% (D10). Genes for which expression was specific to each group at 1 or 3 h after irradiation were identified using statistical procedures including analysis of variance and a two-dimensional hierarchical clustering method. The remaining nine cell lines were subjected to the k-nearest neighbor pattern classification.


RESULTS
The nine test cell lines were successfully classified by their D10 value using 46 and 44 genes for which transcription levels had significantly changed at 1 and 3 h after irradiation, respectively. Of these genes, 25 showed altered expression at both time points in the NRG or RG, but independently were unable to classify the test cell lines.


CONCLUSIONS
Radioresistant cell lines analyzed in this study showed certain radiation-induced changes in gene expression profiles that are different from the profile changes of the more-sensitive cell lines.
Ishikawa
Ken-ichi
K
RadGenomics Project, Frontier Research Center, National Institute of Radiological Sciences, Inage, Chiba, Japan.
Koyama-Saegusa
Kumiko
K
Otsuka
Yoshimi
Y
Ishikawa
Atsuko
A
Kawai
Seiko
S
Yasuda
Kaori
K
Suga
Tomo
T
Michikawa
Yuichi
Y
Suzuki
Masao
M
Iwakawa
Mayumi
M
Imai
Takashi
T
D045744:Cell Line, Tumor / Q000528:radiation effects*; D005347:Fibroblasts / Q000528:radiation effects; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011836:Radiation Tolerance / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors