Identification of radiation-specific responses from gene expression profile

Oncogene. 2002 Dec 5;21(55):8521-8. doi: 10.1038/sj.onc.1205977.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • CD3 Complex / immunology
  • Cell Division
  • Concanavalin A / pharmacology
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic / radiation effects*
  • Humans
  • Jurkat Cells
  • Oligonucleotide Array Sequence Analysis
  • Phytohemagglutinins / pharmacology
  • Radiation, Ionizing
  • Signal Transduction
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / radiation effects

Substances

  • CD3 Complex
  • Phytohemagglutinins
  • Concanavalin A