Document Detail


Loss of cell cycle controls in apoptotic lymphoblasts of the bursa of Fabricius.
MedLine Citation:
PMID:  7812045     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
P E Neiman; C Blish; C Heydt; G Loring; S J Thomas
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular biology of the cell     Volume:  5     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1995-02-06     Completed Date:  1995-02-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  763-72     Citation Subset:  IM    
Affiliation:
Fred Hutchinson Cancer Research Center, Seattle, Washington.
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MeSH Terms
Descriptor/Qualifier:
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:
CA-20068/CA/NCI NIH HHS; CA-57215/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cyclins; 0/Tumor Suppressor Protein p53; EC 2.7.11.22/Cyclin-Dependent Kinases
Comments/Corrections

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