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DNA Research Advance Access published online on March 21, 2006
DNA Research, doi:10.1093/dnares/dsi028
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© The Author 2006. Kazusa DNA Research Institute.
Received September 22, 2005
Revised February 11, 2006

Full Papers

The Role of Trp53 in the Transcriptional Response to Ionizing Radiation in the Developing Brain

J. Verheyde 1, L. de Saint-Georges 2, L. Leyns 3, and M. A. Benotmane 2 *

1 Laboratory of Radiobiology, Studiecentrum voor Kernenergie/Centre d'étude de l'Énergie Nucléaire (SCK•CEN), Boeretang 200, Mol B-2400, Belgium; Laboratory for Cell Genetics, Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium
2 Laboratory of Radiobiology, Studiecentrum voor Kernenergie/Centre d'étude de l'Énergie Nucléaire (SCK•CEN), Boeretang 200, Mol B-2400, Belgium
3 Laboratory for Cell Genetics, Vrije Universiteit Brussel, Pleinlaan 2, Brussels B-1050, Belgium

* To whom correspondence should be addressed.
M. A. Benotmane, E-mail: abenotma{at}sckcen.be


  Abstract

Brain formation results from a series of well-timed consecutive waves of cellular proliferation, migration and differentiation. Acute irradiation during pregnancy selectively interferes with these events to result in malformations such as microcephaly, reduced cortical thickness and mental retardation. In the present study we performed a straight-through cDNA-microarray analysis of the developing mouse brain at embryonic day E13, 3 h after in utero exposure to 50 cGy X-radiation. This dataset was used as an indication of genes involved in different pathways that are activated upon early radiation exposure, and for further evaluation using quantitative PCR (qPCR). Microarray and qPCR data revealed that the main activated pathways in irradiated wild-type embryos are involved in the regulation of a p53-mediated pathway that may lead to cell cycle delay/arrest and increased levels of apoptosis. To define whether the transcriptional radiation response was solely p53 mediated, we analysed the expression of cell cycle regulating genes in a Trp53 null mutant. The modulated expression of cell cycle regulating genes such as cyclins and Cdk genes indicated the induction of a cell cycle arrest, without evidence for the onset of apoptosis. Additional gene-expression studies have shown that various E2F transcription factors may be involved in this event. Together, these results provide a detailed view of the different p53-related mechanisms that are triggered in response to ionizing radiation in the developing brain.

Keywords: cDNA microarray; ionizing radiation; brain development; Trp53; p53.
Communicated by Shoji Tsuji
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