Abstract
The responses to ionizing radiation (IR) in tumors are dependent on cellular context. We investigated radiation-related expression patterns in Jurkat T cells with nonsense mutation in p53 using cDNA microarray. Expression of 2400 genes in γ-irradiated cells was distinct from other stimulations like anti-CD3, phetohemagglutinin (PHA) and concanavalin A (ConA) in unsupervised clustering analysis. Among them, 384 genes were selected for their IR-specific changes to make ‘RadChip’. In spite of p53 status, every type of cells showed similar patterns in expression of these genes upon γ-radiation. Moreover, radiation-induced responses were clearly separated from the responses to other genotoxic stress like UV radiation, cisplatin and doxorubicin. We focused on two IR-related genes, phospholipase Cγ2 (PLCG2) and cytosolic epoxide hydrolase (EPHX2), which were increased at 12 h after γ-radiation in RT–PCR. TPCK could suppress the induction of these two genes in either of Jurkat T cells and PBMCs, which might suggest the transcriptional regulation of PLCG2 and EPHX2 by NF-κB upon γ-radiation. From these results, we could identify the IR-specific genes from expression profiling, which can be used as radiation biomarkers to screen radiation exposure as well as probing the mechanism of cellular responses to ionizing radiation.
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Acknowledgements
We thank Dr Dong-Sup Lee for his helpful discussions and our laboratory members for their helpful inspiration to this study. J-H Kim and J-H Woo are elective students for this project (2001). This work was supported by Nuclear Research Funds from KISTEP to W-Y Park (1999–2001). This study was supported in part by 2001 BK21 project for Medicine, Dentistry and Pharmacy to M-J Kang, C-N Im, C-I Hwang, W-Y Park and J-S Seo.
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Park, WY., Hwang, CI., Im, CN. et al. Identification of radiation-specific responses from gene expression profile. Oncogene 21, 8521–8528 (2002). https://doi.org/10.1038/sj.onc.1205977
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DOI: https://doi.org/10.1038/sj.onc.1205977
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