The authors wished to identify the radiation-induced early transcriptional responses and genes related to individual radiation sensitivity. Seven normal and three radiation sensitive primary human fibroblast cell lines were irradiated with 2 Gy gamma-radiations and RNA isolated 2 h later. Radiation-induced transcriptional alterations and differences in basal gene expression profiles were investigated using Agilent’s Whole Human Genome Oligo Microarray (44000 features) system. Statistically significant (P<0.001) alterations was determined using Agilent’s Feature extraction Image Analysis software. Limited number of genes showed significant radiation-induced responses in normal cells: 109 were up-regulated and 114 were down-regulated. In radiation sensitive fibroblasts 144 genes were up- and 56 genes were down-regulated. When radiation-induced responses were compared in normal and sensitive cells, 28 genes were up- and 2 were down-regulated in all fibroblasts. The radiation-response genes were functionally categorized into the following groups: cell cycle, DNA repair, stress response, energy metabolism, signal transduction and function unknown. When basal gene expression profiles of radiation sensitive strains were compared to normal fibroblasts 60 genes were up- and 150 genes were down-regulated in all sensitive cell lines. We suggest that genes responding to radiation both in normal and sensitive fibroblasts have an inevitable function in radiation response. Genes responding to radiation either only in normal or sensitive cells, and genes whose basal expression profile was altered in all sensitive fibroblasts might contribute to individual radiation sensitivity. The data presented here could contribute to the better understanding of early radiation responses and the development of biomarkers to identify radiation susceptible individuals.
[Proc Amer Assoc Cancer Res, Volume 47, 2006]