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Identification of differentially transcribed genes in human lymphoblastoid cells irradiated with 0.5 Gy of γ-ray and the involvement of low dose radiation inducible CHD6 gene in cell proliferation and radiosensitivity

作者:Huihui Wang, Xiaoqin Long, Zhaoyun Sun, O. Rigaud, Qin-Zhi Xu, Yu‐Chen Huang, J. L. Sui, Bei Bai, Ping‐Kun Zhou · 发表于:International Journal of Radiation Biology · 年份:2006 · DOI:10.1080/09553000600632261 · 被引用次数:35 · 研究领域:Effects of Radiation Exposure、DNA Repair Mechanisms、PARP inhibition in cancer therapy

PURPOSE: To identify candidate genes specifically involved in response to low-dose irradiation in human lymphoblastoid cells; to better clarify the role of the human chromodomain helicase DNA binding protein 6 gene (CHD6), one of these genes, in cell proliferation and radiosensitivity. MATERIALS AND METHODS: DNA microarray technology was used to analyse global transcriptional profile in human lymphoblastoid AHH-1 cells at 4 h after exposure to 0.5 Gy of gamma-ray. Gene expression changes were confirmed by semi-quantitative reverse transcription--polymerase chain reaction (RT-PCR) and Northern blot. RNA interfering technology was employed to knock-down the CHD6 gene in A549 cells. Colony-forming ability was used to analyse radiosensitivity. RESULTS: The microarray assay revealed a set of 0.5 Gy-responsive genes, including 30 up-regulated genes and 45 down-regulated genes. The up-regulated genes include a number of genes involved in: signal transduction pathways, e.g., STAT3, CAMKK2, SIRT1, CREM, MAPK3K7IP2 and GPR56; transcription or DNA-binding, e.g., CHD6, CRSP3, SNURF, SH2 domain binding protein 1 and MIZF. Some of the down-regulated genes are involved in: cytoskeleton and cell movement (WASF2, LCP1, MSN, NIPSNAP1, KIF2C); DNA replication and repair (MCM2, MCM3, MCM7 and XRCC-4). Radiation-increased expression of CHD6 was also found in A549 cells and HeLa cells. The sustained CHD6 induction was restricted to relatively low doses (0.2 Gy or 0.5 Gy), no change occurring after...