| Loss of cell cycle controls in apoptotic lymphoblasts of the bursa of Fabricius. | |
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MedLine Citation:
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PMID: 7812045 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lymphoblasts of the normal embryonic follicles of the chicken bursa of Fabricius undergo rapid apoptosis when exposed to gamma-radiation or when cell-cell contacts are disrupted by mechanical dispersion in short term culture. We have observed previously that overexpression of v-myc sensitizes preneoplastic bursal lymphoblasts to induction of cell death, whereas resistance to induced cell death is acquired during progression to neoplasia. In this study we observed extensive DNA degradation in the large majority of the lymphoblast population within the first hour after dispersion-induced apoptosis. Paradoxically these cells continued to progress into S-phase with the bulk of DNA cleavage and death occurring in S-phase cells (i.e., in cells with more than 2C and less than 4C DNA content). We confirmed the S phase status of apoptotic cells by determining that detection of nuclear cyclin A in individual cells also corresponded with detection of DNA breakage. Levels of cyclin E, cyclin E-dependent H1 histone kinase, and p53 proteins were maintained during dispersion-induced DNA cleavage. gamma-radiation failed either to inhibit cell cycle progression or to raise p53 levels in dispersed bursal lymphoblasts. In intact bursal follicles low doses of gamma-radiation induced p53 whereas higher, apoptosis-inducing doses failed to induce p53 or prevent G1 to S-phase progression. These results suggest that normal DNA damage-induced cell cycle checkpoint controls are lost or overridden when apoptosis is induced in bursal lymphoblasts. |
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Authors:
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P E Neiman; C Blish; C Heydt; G Loring; S J Thomas |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular biology of the cell Volume: 5 ISSN: 1059-1524 ISO Abbreviation: Mol. Biol. Cell Publication Date: 1994 Jul |
Date Detail:
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Created Date: 1995-02-06 Completed Date: 1995-02-06 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9201390 Medline TA: Mol Biol Cell Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 763-72 Citation Subset: IM |
Affiliation:
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Fred Hutchinson Cancer Research Center, Seattle, Washington. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* Bursa of Fabricius / cytology*, radiation effects Cell Cycle / physiology*, radiation effects Cells, Cultured Chick Embryo Cyclin-Dependent Kinases / analysis* Cyclins / analysis* DNA Damage* DNA Replication Gamma Rays Lymphocytes / cytology*, radiation effects S Phase Specific Pathogen-Free Organisms Tumor Suppressor Protein p53 / analysis* |
| Grant Support | |
ID/Acronym/Agency:
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CA-20068/CA/NCI NIH HHS; CA-57215/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclins; 0/Tumor Suppressor Protein p53; EC 2.7.11.22/Cyclin-Dependent Kinases |
| Comments/Corrections | |
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