Analysis of gene-expression profiles after gamma irradiation of normal human fibroblasts.
OBJECTIVE
To understand comprehensive transcriptional profile of normal human fibroblast in response to irradiation.


METHODS
To identify genes whose expression is influenced by gamma radiation, we used a cDNA microarray to analyze expression of 23,000 genes in normal human fibroblasts at 7 timepoints (1, 3, 6, 12, 24, 48, and 72 hours) after 5 different doses (0.5, 2, 5, 15, and 50 Gy) of exposure.


RESULTS
Among the genes that showed altered expression patterns, some were already known to be regulated by irradiation, for instance ODC, EGR1, FGF2, PCNA, PKC, and several p53-target genes, including p53DINP1, BTG2, GADD45, and MDM2. The time course of each dose showed that from 350 to 600 genes were affected as to their expression; induction profiles characteristic to each dose were demonstrated. Of the total identified, only 89 genes were up-regulated; the vast majority was down-regulated over the 72-hour time course. We identified 21 genes that were distinctly induced by irradiation; 11 of them were functionally known, and 6 of those were p53-target genes.


CONCLUSIONS
The results underscored the complexity of the transcriptional responses to irradiation, and the data should serve as a basis for global characterization of radiation-regulated genes and pathways.
Tachiiri
Seiji
S
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. tachiiri@kuhp.kyoto-u.ac.jp
Katagiri
Toyomasa
T
Tsunoda
Tatsuhiko
T
Oya
Natsuo
N
Hiraoka
Masahiro
M
Nakamura
Yusuke
Y
D005347:Fibroblasts / Q000528:radiation effects*; D005720:Gamma Rays; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis