Comprehensive analysis of time- and dose-dependent patterns of gene expression in a human mesenchymal stem cell line exposed to low-dose ionizing radiation.
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.
Jin
Young-Woo
YW
Division of Radiation Effect Research, Radiation Health Research Institute of KHNP, Seoul 132-703, Korea.
Na
Young-Ji
YJ
Lee
Young-Ju
YJ
An
Sungkwan
S
Lee
Jung Eun
JE
Jung
Meeseon
M
Kim
Heesun
H
Nam
Seon Young
SY
Kim
Cha Soon
CS
Yang
Kwang Hee
KH
Kim
Seung Up
SU
Kim
Woo Kyung
WK
Park
Woong-Yang
WY
Yoo
Keun-Young
KY
Kim
Chong Soon
CS
Kim
Ju Han
JH
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*