title: Comprehensive analysis of time- and dose-dependent patterns of gene expression in a human mesenchymal stem cell line exposed to low-dose ionizing radiation.
abstract: We focused on the transcriptional responses induced by low and very low doses of ionizing radiation with time effect. Regardless of their importance only a few limited studies have been done. Here we applied a 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 h after exposure. The essential transcriptional responses were identified according to dose and time. A total of 6,016 genes showed altered expression patterns at more than one time point or dose level 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 were 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. A highly non-linear relationship between the IR dose and the transcriptional relative response was obtained from the dose-dependent group. The time-dependent group also exhibited a non-linear relationship as the complex effect group did. Some of the early-reactive-phase (1-4 h) genes showed a 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 a 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.
authors: Division of Radiation Effect Research, Radiation Health Research Institute of KHNP, Seoul 132-703, Korea.
authors: Young-Woo
authors: YW
authors: Jin
authors: Young-Ji
authors: YJ
authors: Na
authors: Young-Ju
authors: YJ
authors: Lee
authors: Sungkwan
authors: S
authors: An
authors: Jung Eun
authors: JE
authors: Lee
authors: Meeseon
authors: M
authors: Jung
authors: Heesun
authors: H
authors: Kim
authors: Seon Young
authors: SY
authors: Nam
authors: Cha Soon
authors: CS
authors: Kim
authors: Kwang Hee
authors: KH
authors: Yang
authors: Seung Up
authors: SU
authors: Kim
authors: Woo Kyung
authors: WK
authors: Kim
authors: Woong-Yang
authors: WY
authors: Park
authors: Keun-Young
authors: KY
authors: Yoo
authors: Chong Soon
authors: CS
authors: Kim
authors: Ju Han
authors: JH
authors: Kim
mesh_terms: D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D015870:Gene Expression / Q000528:radiation effects*; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D059630:Mesenchymal Stem Cells / Q000528:radiation effects*; D020411:Oligonucleotide Array Sequence Analysis; D011839:Radiation, Ionizing; D013995:Time; D014158:Transcription, Genetic / Q000528:radiation effects*