Identification of radiation-specific responses from gene expression profile.
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 gamma-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 gamma-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 Cgamma2 (PLCG2) and cytosolic epoxide hydrolase (EPHX2), which were increased at 12 h after gamma-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-kappaB upon gamma-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.
Park
Woong-Yang
WY
Ilchun Molecular Medicine Institute, Seoul National University, Chongnogu, Seoul, Korea.
Hwang
Chang-Il
CI
Im
Chang-Nim
CN
Kang
Min-Ji
MJ
Woo
Jang-Hee
JH
Kim
Ju-Hoon
JH
Kim
Yon Su
YS
Kim
Ju-Han
JH
Kim
Ho
H
Kim
Kyung-A
KA
Yu
Hyung-Jin
HJ
Lee
Sue-Jae
SJ
Lee
Yun-Sil
YS
Seo
Jeong-Sun
JS
D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D019169:Jurkat Cells; D020411:Oligonucleotide Array Sequence Analysis; D010835:Phytohemagglutinins / Q000494:pharmacology; D011839:Radiation, Ionizing; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects
D017252:CD3 Complex; D010835:Phytohemagglutinins; D003208:Concanavalin A