Document Detail


Spontaneous cell transformation: karyoplasts derived from multinucleated cells produce new cell growth in senescent human epithelial cell cultures.
MedLine Citation:
PMID:  15479119     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously, it was shown that SV40-induced cell transformation of human diploid (2N), epithelial cells was a dynamic process of nuclear and cellular events. In this process, nuclei of polyploid (above 2N) cells broke down into multinucleated cells (MNCs) by amitotic division. An induced mass karyoplast (i.e., small cell with reduced amount of cytoplasm) budding process from the MNCs produced transformed cells with extended life span (EL) and altered morphology. In this study, without the use of SV40 and no induction of karyoplast budding, the same sequence of cellular events was found to occur spontaneously for the same type of cells at replicative senescence (no mitosis). These cell transformation events were followed by phase-contrast photography of living cell cultures. Primary, diploid, epithelial cell cultures grew for two to three passages and then entered senescence. Cells remaining in the cultures after widespread cell death (mortality stage 1; M1) developed the typical large, flat-cell morphology of senescence with increased cytoplasmic volume. Some of these cells were MNCs, mostly with two to four nuclei. Cytokinesis in MNCs and spontaneous karyoplast budding from MNCs were observed, and new, limited EL cell growth was present either in foci of cells or as prolonged cell growth over one to two passages. At the end of their replicative phase, the EL cells entered another death crisis (M2) from which no cells survived. In M2-crisis, rarely transformed cells appear with immortal cell growth characteristics (i.e., cell lines). Numerous examples of fragmentation or amitosis of polyploid nuclei in the production of multinucleated cells (MNCs) are presented. Such nuclear divisions produced nuclei with unequal sizes, which suggest unbalanced chromosomal segregations. The nuclear and cellular events in cell transformation are compared with a natural (no induction) occurrence of MNC-offspring cells in mammalian placentas. The possibility of a connection between these two processes is discussed. And finally the difference in the duration of EL cell growth from SV40-MNCs versus from senescent-MNCs is ascribed to increased mutational load in SV40-induced MNCs as compared with that in senescence MNCs.
Authors:
Kirsten H Walen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  In vitro cellular & developmental biology. Animal     Volume:  40     ISSN:  1071-2690     ISO Abbreviation:  In Vitro Cell. Dev. Biol. Anim.     Publication Date:    2004 May-Jun
Date Detail:
Created Date:  2004-10-13     Completed Date:  2004-11-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9418515     Medline TA:  In Vitro Cell Dev Biol Anim     Country:  United States    
Other Details:
Languages:  eng     Pagination:  150-8     Citation Subset:  IM    
Affiliation:
Viral and Rickettsial Disease Laboratory, California Department of Health Services, 850 Marina Bay Parkway, Richmond, California 94804, USA. psavage@dhs.ca.gov
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MeSH Terms
Descriptor/Qualifier:
Amniocentesis / methods
Cell Aging / genetics,  physiology*
Cell Line, Transformed / cytology*,  metabolism
Cell Nucleus
Cell Transformation, Viral
Chromosome Breakage / physiology
Cytokinesis / physiology
DNA Fragmentation / physiology
Epithelial Cells / cytology*,  metabolism
Female
Giant Cells / cytology*,  metabolism
Humans
Microscopy, Phase-Contrast / methods
Placenta / cytology,  physiology
Polyploidy
Pregnancy
Simian virus 40 / physiology

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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