Delayed effects of exposure to a moderate radiation dose on transcription profiles in human primary fibroblasts.

Abstract

Ionizing radiation (IR) is used in a wide variety of medical and nonmedical applications and poses a potential threat to human health. Knowledge of changes in gene expression in irradiated cells may be helpful for the establishment of effective paradigms for radiation protection. IR-induced DNA damage triggers a complex cascade of signal transduction. Recently, genome-wide approaches have allowed the detection of alterations in gene expression across a wide range of radiation doses. However, the delayed or long-term biological effects of mild-doses of IR remain largely unknown. The main objective of the present study was to investigate the effects of a moderate dose of gamma-rays (50 cGy) on gene expression 6 days post-irradiation. Gene expression using cDNA microarrays revealed statistically significant changes in the expression of 59 genes (FDR < 0.07), whose functions are related to cell-cycle control, protein trafficking, ubiquitin cycle, Rho-GTPAse pathway, protein phosphatase signalization, oxidoreductase control, and stress response. A set of 464 genes was also selected by a less stringent approach, and we demonstrate that this broader set of genes can efficiently distinguish the irradiated samples from the unirradiated, defining a long-term IR signature in human primary fibroblasts. Our findings support the existence of persistent responses to mild doses of IR detectable by changes in gene expression profiles. These results provide insight into delayed effects observed in human primary cells as well as the role of long-term response in neoplastic transformation. Environ.