Nitroreductase-mediated cell ablation is very rapid and mediated by a p53-independent apoptotic pathway

Gene Ther. 1999 May;6(5):764-70. doi: 10.1038/sj.gt.3300873.

Abstract

Nitroreductase (NTR)-mediated selective cell ablation using the prodrug CB1954 has been achieved in vivo by targeting the nitroreductase gene to the luminal cells of the mammary gland in transgenic mice. We report that the cell ablation occurs very rapidly, starting as early as 7 h after administration of the prodrug. By cross-breeding the BLG-NTR transgenic mice to a p53-deficient mouse strain, we have generated BLG-NTR transgenic mice on a p53 null background and tested NTR-mediated cell ablation in these mice. The transgenic mice lacking a functional p53 gene showed cell ablation at a similar level compared with p53 wild-type transgenic mice, showing that functional p53 is not required for CB1954-NTR mediated cell death. These results provide further support for using this system in anti-cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Apoptosis / genetics*
  • Aziridines / administration & dosage
  • Female
  • Genes, p53
  • Genetic Therapy / methods*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Mammary Glands, Animal / pathology
  • Mice
  • Mice, Transgenic
  • Neoplasms / therapy*
  • Nitroreductases / genetics*
  • Prodrugs / administration & dosage
  • Time Factors

Substances

  • Antineoplastic Agents
  • Aziridines
  • Prodrugs
  • tretazicar
  • Nitroreductases