Modulations of glucocorticoid-induced apoptosis linked to the p53 deletion and to the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1)

Oncogene. 1999 Jul 22;18(29):4282-5. doi: 10.1038/sj.onc.1202719.

Abstract

We have analysed the effects of p53 and of the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1) located on chromosome 16 on glucocorticoid- and radiation-induced in vivo apoptosis of thymocytes. For those analyses, we used Rapop1 semicongenic mice heterozygous for the STS and BALB/cHeA alleles in the chromosomal segment containing Rapop1 in the BALB/cHeA background, mice bearing a p53 deficient allele in the BALB/cHeA background and the genetic crosses between these mice. The p53 wild type mice with a STS/A allele at the Rapop1 locus were less susceptible to both radiation- and glucocorticoid-induced apoptosis than those with homozygous BALB/cHeA alleles at this locus. Surprisingly, glucocorticoid-induced apoptosis was enhanced in the p53 hemizygous mice and considerably increased in the p53 nullizygous mice. In contrast, a sizable reduction of radiation-induced apoptosis was seen in the p53 hemizygous mice. The low susceptiblity to glucocortocoid-induced apoptosis linked to the STS allele of Rapop1 was less pronounced in the p53 hemizygous mice and a diminished effect of Rapop1 on radiation-induced apoptosis was seen in these mice. Although it remains to be established whether the genes modulating glucocortocoid-induced apoptosis are identical to p53 and Rapop1, our data suggest that p53 and Rapop1 may participate in glucocorticoid-induced apoptosis of thymocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Apoptosis / radiation effects
  • Crosses, Genetic
  • Dexamethasone / pharmacology*
  • Drug Resistance / genetics
  • Genes, Regulator*
  • Genes, p53*
  • Genotype
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Radiation Tolerance / genetics*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / radiation effects
  • Tumor Suppressor Protein p53 / deficiency*
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Tumor Suppressor Protein p53
  • Dexamethasone