Fluorescent cDNA microarray hybridization reveals complexity and heterogeneity of cellular genotoxic stress responses

Sally A. Amundson, Mike Bittner, Yidong Chen, Jeffrey Trent, Paul Meltzer, Albert J. Fornace

Research output: Contribution to journalArticle

285 Scopus citations

Abstract

The fate of cells exposed to ionizing radiation (IR) may depend greatly on changes in gene expression, so that an improved view of gene induction profiles is important for understanding mechanisms of checkpoint control, repair and cell death following such exposures. We have used a quantitative fluorescent cDNA microarray hybridization approach to identify genes regulated in response to γ-irradiation in the p53 wild-type ML-1 human myeloid cell line. Hybridization of the array to fluorescently-labeled RNA from treated and untreated cells was followed by computer analysis to derive relative changes in expression levels of the genes present in the array, which agreed well with actual quantitative changes in expression. Forty-eight sequences, 30 not previously identified as IR-responsive, were significantly regulated by IR. Induction by IR and other stresses of a subset of these genes, including the previously characterized CIP1/WAF1, MDM2 and BAX genes, as well as nine genes not previously reported to be IR-responsive, was examined in a panel of 12 human cell lines. Responses varied widely in cell lines with different tissues of origin and different genetic backgrounds, highlighting the importance of cellular context to genotoxic stress responses. Two of the newly identified IR-responsive genes, FRA-1 and ATF3, showed a p53-associated component to their IR-induction, and this was confirmed both in isogenic human cell lines and in mouse thymus. The majority of the IR-responsive genes, however, showed no indication of p53-dependent regulation, representing a potentially important class of stress-responsive genes in leukemic cells.

Original languageEnglish (US)
Pages (from-to)3666-3672
Number of pages7
JournalOncogene
Volume18
Issue number24
DOIs
StatePublished - Jun 17 1999
Externally publishedYes

Keywords

  • Genotoxic stress
  • Ionizing radiation
  • Leukemia
  • cDNA microarray
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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