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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1995-9-14
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pubmed:abstractText |
To better understand the molecular basis of radiation-induced cell death, we studied the role of the bcl-2 oncogene and the p53 tumor suppressor gene in this process. A temperature-sensitive mutant of murine p53 (p53Val-135) and/or bcl-2 was transfected into murine erythroleukemia cells (MEL, DP16-1, which are null in p53). We demonstrate that radiation-induced cell death occurs by both p53-dependent and -independent pathways and overexpression of bcl-2 modulates both pathways. When viability was measured 24 h post-radiation, cells that had been briefly exposed to wtp53 immediately after X-ray irradiation had decreased survival as compared to unirradiated cells expressing wtp53 or X-ray irradiated DP16-1 cells. However, at later times X-ray irradiated parental DP16-1 cells also had decreased survival compared to the unirradiated control. This decrease in survival began 48 h following radiation. Bcl-2 prevented radiation-induced cell death in DP16-1 cells expressing wtp53 and delayed radiation-induced cell death in DP16-1 cells without wtp53. X-ray irradiated cells expressing wtp53 displayed microscopic and biochemical characteristics consistent with cell death due to apoptosis. DP16-1 cells which were untransfected or co-transfected with wtp53 and bcl-2 displayed characteristics of cells undergoing necrosis. These results suggest that radiation-induced cell death occurs by both p53-dependent and p53-independent pathways. The p53-dependent pathway results in cell death via apoptosis and occurs approximately 24 h following radiation. The p53-independent pathway does not appear to involve apoptosis and occurs at a later time, starting 48 h after X-ray exposure. Thus, bcl-2 protects cells from p53-dependent radiation-induced apoptotic cell death and attenuates p53-independent radiation-induced cell death.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0143-3334
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
16
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1761-7
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pubmed:dateRevised |
2005-11-17
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pubmed:meshHeading |
pubmed-meshheading:7634401-Animals,
pubmed-meshheading:7634401-Apoptosis,
pubmed-meshheading:7634401-Cells, Cultured,
pubmed-meshheading:7634401-Leukemia, Erythroblastic, Acute,
pubmed-meshheading:7634401-Mice,
pubmed-meshheading:7634401-Proto-Oncogene Proteins,
pubmed-meshheading:7634401-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:7634401-Tumor Suppressor Protein p53,
pubmed-meshheading:7634401-X-Ray Therapy
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pubmed:year |
1995
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pubmed:articleTitle |
Bcl-2 protects murine erythroleukemia cells from p53-dependent and -independent radiation-induced cell death.
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pubmed:affiliation |
Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor 48109, USA.
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pubmed:publicationType |
Journal Article
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