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Published on: July 3, 2015
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.
Abstract:
Apoptosis is a physiological phenomenon occurring during embryonic development, T and B cell maturation, and endocrine-induced atrophy. It can be initiated by various agents and has been considered to be related to the expression of the oncosuppressor p53 gene. In this review, p53 gene-targeting mice were used to study the effect of p53 gene status on the induction of apoptosis in bone marrow cells by gamma-ray irradiation. The results showed that homozygous null (p53 -/-) murine bone marrow cells were more resistant to the induction of apoptosis by radiation than other genotypes (heterozygous, p53 +/- and wild type, p53 +/+). The percentage of apoptotic cells in p53 +/+ mice was about three times that in p53 -/- mice at 4 hr after 6 Gy gamma-irradiation, and the analysis of the apoptosis-characteristic DNA ladder further supported these findings. We found that the homozygous null mice also can undergo apoptosis after irradiation. This suggested that there is another independent apoptotic p53 gene mechanism in irradiated murine bone marrow cells. Thus, in murine bone marrow cells, both p53 gene-dependent and -independent apoptosis occurred after irradiation. In our previous work, an increase in survival of hemopoietic progenitor cells after irradiation in vitro in p53 gene deletion mice was observed. This increase is closely related to the inhibition of apoptosis in bone marrow cells in p53 gene deletion mice.
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.
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