Document Detail

Conversion to the terminally differentiated state during treatment of NG108-15 neural tumor cells with 1-beta-D-arabinofuranosylcytosine in defined medium.
MedLine Citation:
PMID:  2910463     Owner:  NLM     Status:  MEDLINE    
Differentiation of cells of the neural tumor hybrid cloned cell line NG108-15 begins stochastically upon transfer to a serum-free defined medium (A. Krystosek, J. Cell. Physiol., 125: 319-329, 1985). Such cultures in N2 medium contain both proliferating and neurite-forming cells (which are not mutally exclusive subpopulations). Addition of 1-beta-D-arabinofuranosylcytosine (ara-C) to NG108-15 cells in N2 medium yielded cultures with a highly differentiated appearance. Investigation of the nature of this effect revealed that ara-C did not increase the probability that cells would enter the differentiation pathway; it did, however, completely abolish proliferation. The early kinetics of neurite formation were similar in control and treated cultures. This was followed by a phase in which ara-C-treated cells underwent continuous rapid maturation including normalization of nucleolar features. Loss of proliferative potential of treated cells was tested in a drug-free serum challenge protocol. Permanently postmitotic cells (i.e., cells which failed to divide even once) were shown to accumulate with time of ara-C pretreatment; this represented 59% of total cells at day 3 and 94% at day 7 of treatment. Thus, the bulk of the population can commit to terminal differentiation. Even among the minority of cells capable of 1-2 rounds of division in the challenge incubation, cessation of proliferation was more likely than continuous colonial growth, suggesting that a profound phenotypic alteration had occurred. The results show that advanced morphological maturation and the step(s) of terminal neuronal differentiation can be achieved in this cell line in response to a cancer chemotherapeutic agent and that this drug is a more complete inducer than compounds which modulate the cyclic AMP system.
A Krystosek
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer research     Volume:  49     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1989 Jan 
Date Detail:
Created Date:  1989-02-22     Completed Date:  1989-02-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  450-8     Citation Subset:  IM    
Department of Biochemistry, Biophysics, and Genetics, University of Colorado Health Sciences Center, Denver 80206.
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MeSH Terms
Cell Differentiation / drug effects
Cell Division / drug effects
Cell Nucleolus / drug effects
Cell Survival / drug effects
Culture Media
Cytarabine / pharmacology*
Neuroblastoma / pathology*
Grant Support
Reg. No./Substance:
0/Culture Media; 147-94-4/Cytarabine

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