Apoptosis in bone marrow cells of mice with different p53 genotypes after gamma-rays irradiation in vitro

Y F Cui1, P K Zhou, L B Woolford

  • 1Institute of Radiation Medicine, Beijing, P.R. China.

Insights

The p53 tumor suppressor gene influences apoptosis in bone marrow cells following radiation exposure. Mice lacking the p53 gene exhibit resistance to radiation-induced apoptosis, indicating a p53-independent pathway.

Area of Science:

  • Cell Biology
  • Genetics
  • Radiation Biology

Background:

  • Apoptosis, or programmed cell death, is crucial for development and tissue homeostasis.
  • The oncosuppressor p53 gene plays a recognized role in initiating apoptosis.
  • Radiation exposure can trigger apoptosis in various cell types, including bone marrow cells.

Purpose of the Study:

  • To investigate the role of the p53 gene status in radiation-induced apoptosis of murine bone marrow cells.
  • To compare apoptosis induction in bone marrow cells with different p53 gene genotypes (p53 -/-, p53 +/-, p53 +/+).
  • To explore the existence of p53-independent apoptotic mechanisms in response to irradiation.

Main Methods:

  • Utilized p53 gene-targeting mice (homozygous null, heterozygous, and wild type).
  • Exposed murine bone marrow cells to gamma-ray irradiation (6 Gy).
  • Quantified apoptotic cells and analyzed DNA laddering at 4 hours post-irradiation.

Main Results:

  • Homozygous null (p53 -/-) murine bone marrow cells showed increased resistance to radiation-induced apoptosis compared to p53 +/- and p53 +/+ genotypes.
  • The percentage of apoptotic cells in wild-type (p53 +/+) mice was approximately three times higher than in p53 -/- mice.
  • DNA ladder analysis confirmed reduced apoptosis in p53 -/- mice, yet apoptosis was still observed, suggesting an alternative pathway.

Conclusions:

  • Both p53-dependent and p53-independent apoptotic pathways are activated in murine bone marrow cells following gamma-ray irradiation.
  • The absence of the p53 gene confers resistance to radiation-induced apoptosis in bone marrow cells.
  • Previous findings of increased hemopoietic progenitor cell survival in p53-deleted mice are linked to apoptosis inhibition.