Purpose: To understand comprehensive transcriptional profile of normal human fibroblast in response to irradiation.
Methods and materials: 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.