Genome-wide gene expression changes in normal human fibroblasts in response to low-LET gamma-radiation and high-LET-like 125IUdR exposures.

Functional genomics studies were carried out to characterize the transcriptional response of normal human fibroblasts to ionizing radiation (IR) of different types. To this end, lung fibroblast IMR-90 cultures were exposed either to external beam gamma-radiation or to internal irradiation from decay of (125)I-labeled deoxyuridine ((125)IUdR) incorporated into the cellular DNA. A relatively small dose of 1 Gy of gamma-radiation was delivered to cell cultures either at a high dose-rate (HDR, 1 Gy, 1 min) or at a low dose-rate (LDR, 1 Gy, 22 h). More than 41,000 transcripts were assayed by oligo DNA microarray featuring all known and predicted genes in human genome. Gene expression profiles following gamma-radiation and decays of high-linear energy transfer (LET)-like (125)I share the majority of genes in common, indicating the involvement of similar pathways in signal transduction after IR exposures of different modalities. Gene Ontology (GO) analysis revealed that the oxidative phosphorylation, metabolism of nt, protein kinase cascade and cell cycle are among the up-regulated biological processes mostly affected by gamma-radiation in IMR-90 cells. The translational elongation, negative regulation of cell growth, antigen processing and protein targeting are down-regulated following IR exposures. About one-third of genes differentially expressed following either HDR or LDR gamma-radiation exposures in the same absorbed dose were different, indicating the involvement of distinct transcriptional programs in cellular response to irradiation delivered with the different dose rates.