Cellular events and the pattern of p53 protein expression following cyclophosphamide-initiated cell death in various organs of developing embryo

Arkady Torchinsky, Irena Ivnitsky, Shoshana Savion, Jeana Shepshelovich, Marat Gorivodsky, Amos Fein, Howard Carp, Dov Schwartz, Janne Frankel, Varda Rotter, Vladimir Toder

Research output: Contribution to journalArticlepeer-review

Abstract

This study was aimed at characterizing the temporal patterns of cell responses and p53 protein expression in the limbs, head, and liver of embryos responding to cyclophosphamide (CP)-induced teratogenic insult. ICR murine embryos were examined 24, 48, or 72 h after injection of 40 mg/kg CP on day 12 of pregnancy. The cellular events and temporal pattern of p53 protein expression were determined by FACS analysis and by TUNEL (apoptosis) in the head, limbs, and liver of the embryos. All tested organs showed apoptosis and a significantly decreased proportion of live cells after 24 h. Subsequent events were organ-dependent. In the liver, there were no dysmorphic events at any time and excessive cell death had been almost compensated for by 48 h. Compensation was preceded by G1 arrest and accompanied by an increased level of p53 protein in surviving cells. Excessive cell death in the head and the limbs resulted in structural anomalies. In the head, there was an increased level of p53 protein and G1 arrest after 24 h and the number of live cells at 48 h was equal to that seen in earlier samples, despite apoptosis. In the limbs, however, only isolated viable cells were seen by 48 h, but there was no increased level of p53 protein or G1 arrest. Results of this study suggest that the differential sensitivity of tested organ systems to CP may be associated with differences in cellular events following CP-initiated cell death. They also suggest that the input of p53 in determining the response of these organ systems to CP-induced teratogenic insult may be different.

Original languageEnglish
Pages (from-to)353-367
Number of pages15
JournalTeratogenesis Carcinogenesis and Mutagenesis
Volume19
Issue number5
DOIs
StatePublished - 1999

Keywords

  • Apoptosis
  • Cell cycle
  • Cyclophosphamide
  • P53
  • Teratogens

Fingerprint

Dive into the research topics of 'Cellular events and the pattern of p53 protein expression following cyclophosphamide-initiated cell death in various organs of developing embryo'. Together they form a unique fingerprint.

Cite this