Comprehensive analysis of time and dose-dependent patterns of gene expression in a human mesenchymal stem cell line exposed to low-dose ionizing radiation

Complete text of publication follows. We focus on transcriptional responses induced by low and very low doses of ionizing radiation with time effect. A few and limited studies have been done regardless of their importance. Here we have applied large-scale gene transcript profile to elucidate the genes and biological pathways. Immortalized human mesenchymal stem cells were irradiated with 0.01, 0.05, 0.2 and 1 Gy of gamma radiation and total RNA was extracted from each cell line at 1, 4, 12 and 48 hours after exposure. The essential transcriptional responses were identified according to does and time. The 6,016 genes showed altered expression patterns at more than one time points or dose levels among the investigated 10,800 genes. Genes that showed dose dependent expression responses were involved in signal transduction, regulation of transcription, proteolysis, peptidolysis and metabolism. Those that showed time-dependent responses could be divided into two distinct groups: the up-and-down group was associated with 'cellular defense mechanisms' such as apoptosis, cell adhesion, stress response and immune response and the down-and-up group with 'fundamental cellular processes' such as DNA replication, mitosis, RNA splicing, DNA repair and translation initiation. Genes showing both dose-and-time dependent responses exhibited a mixture of both features. Highly nonlinear relationship between IR dose and transcriptional relative response are obtained from the dose dependent group. Time-dependent group also has nonlinear relationship as complex effect group does. Some of the early-reactive-phase (1 - 4 h) genes showed differential expression response to 0.01, 0.05 and 0.2 Gy but were unresponsive to 1 Gy. Some of the late-recovery-phase (12 - 48 h) genes showed differential expression to 1 Gy but were relatively unresponsive to other doses. We further characterized the gene-expression patterns that could be implicated in the molecular mechanism of the cellular responses to low and very low-dose irradiation.