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.
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Acknowledgements
We thank Drs LA Donehower and A Bradley for their kind gift of p53 deficient mice. We also thank Drs J Allen, GG Gomez and AAM Hart of The Netherlands Cancer Institute for their helpful discussion during preparation of this paper. This publication is partly supported by a research subsidy from the Showa Shell Sekiyu Environmental Research Foundation to Dr N Mori, by a grant from the Japan Atomic Energy Research Institute, by the contract of the Nuclear Safety Research Association to Dr M Okumoto, and by a grant from the Dutch Cancer Foundation to Dr P Demant.
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Mori, N., Yamate, J., Stassen, A. et al. Modulations of glucocorticoid-induced apoptosis linked to the p53 deletion and to the apoptosis susceptibility gene Rapop1 (Radiation-induced apoptosis 1). Oncogene 18, 4282–4285 (1999). https://doi.org/10.1038/sj.onc.1202719
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DOI: https://doi.org/10.1038/sj.onc.1202719