Modulations of glucocorticoid-induced apoptosis linked to the p53 deletion and to the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1).
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.
Mori
N
N
Department of Applied Bioscience, Research Institute for Advanced Science and Technology, Osaka Prefecture University, Sakai, Japan.
Yamate
J
J
Stassen
A P
AP
Oka
S
S
Okumoto
M
M
Tsubura
A
A
Akamatsu
T
T
Sakuma
S
S
Demant
P
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D003433:Crosses, Genetic; D003907:Dexamethasone / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D005809:Genes, Regulator; D016158:Genes, p53; D005838:Genotype; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011836:Radiation Tolerance / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000502:physiology
D016159:Tumor Suppressor Protein p53; D003907:Dexamethasone