Microarray analysis of genes in fetal central nervous system after ethylnitrosourea administration

Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):255-60. doi: 10.1002/bdrb.20045.


Background: Ethylnitrosourea (ENU), a monofunctional alkylating agent, induces apoptosis and cell cycle arrest in neuroepithelial cells, neural stem cells in the fetal central nervous system (CNS). These effects occur immediately after the administration of ENU to pregnant animals resulting in fetal brain anomalies and long-term effects include brain tumors in the offspring.

Methods: Changes in gene expression were investigated in the fetal CNS after ENU administration to pregnant rats using microarray to identify the genes involved in the injury and recovery of the fetal CNS.

Results: The up-regulation of 21 genes in injury and 15 genes in recovery phases and down-regulation of 5 genes in injury and 3 genes in recovery phases were identified. The genes up-regulated in the injury phase contained p53-target genes that mediate apoptosis and cell cycle arrest, and those in the recovery phase contained cell proliferation-promoting genes. The genes down-regulated in the injury phase contained cholesterol biosynthesis-related genes. In addition, there were some genes that have not been identified to be involved in the CNS injury and recovery.

Conclusions: The present study will provide a better understanding of the mechanisms of development, regeneration and carcinogenesis of the CNS as well as the mechanisms of ENU-induced fetal CNS injury and recovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylating Agents / administration & dosage
  • Alkylating Agents / toxicity*
  • Animals
  • Apoptosis / genetics
  • Cell Cycle / drug effects
  • Down-Regulation
  • Ethylnitrosourea / administration & dosage
  • Ethylnitrosourea / toxicity*
  • Female
  • Fetus / drug effects*
  • Fetus / innervation
  • Gene Expression / drug effects*
  • Oligonucleotide Array Sequence Analysis
  • Pregnancy
  • Prenatal Injuries*
  • Rats
  • Telencephalon / drug effects*
  • Telencephalon / embryology
  • Telencephalon / metabolism
  • Up-Regulation


  • Alkylating Agents
  • Ethylnitrosourea