Document Detail

Sister chromatid exchanges and DNA topoisomerase II inhibitors: effect of low concentrations of etoposide (VP-16) in ataxia telangiectasia lymphoblastoid cell lines.
MedLine Citation:
PMID:  9508359     Owner:  NLM     Status:  MEDLINE    
The correlation between etoposide (VP-16) cytotoxicity and the induction of sister chromatid exchanges (SCEs) suggested that the promotion of DNA recombination events may be crucial for the activity of antitopoisomerase drugs. To further evaluate this hypothesis, we investigated the correlation between VP-16 induction of SCEs, chromosomal aberrations and cell cycle alterations in lymphoblastoid cell lines derived from patients affected by ataxia telangiectasia (AT), whose cells are known as hypersensitive to the cytotoxic and clastogenic activity of DNA topoisomerase II inhibitors. Our present study has shown that AT homozygous and heterozygous cell lines exposed to low VP-16 concentrations, although hypersensitive to the induction of chromosomal aberrations, exhibit an induction of SCEs comparable to that found in normal cell lines. Moreover, while the clastogenic effect of the drug was directly correlated to the reduction of the mitotic index, the enhancement of SCE frequencies, obtained over the same range of VP-16 concentrations, was not paralleled by a modification of proliferation index. Thus, these results suggest that etoposide retains in AT cells a strong clastogenic and cytostatic activity which is independent from DNA recombination events and which may be important for the induction of cell death by this kind of drug.
C Fantini; P Vernole; B Tedeschi; D Caporossi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mutation research     Volume:  412     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  1998 Jan 
Date Detail:
Created Date:  1998-04-07     Completed Date:  1998-04-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  1-7     Citation Subset:  IM    
Department of Public Health and Cellular Biology, University of Tor Vergata, Rome, Italy.
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MeSH Terms
Ataxia Telangiectasia / genetics
Cell Division / drug effects
Cell Line
Cell Line, Transformed
DNA Topoisomerases, Type II / antagonists & inhibitors*
Enzyme Inhibitors / toxicity*
Etoposide / toxicity*
Herpesvirus 4, Human
Mitotic Index / drug effects
Mutagens / toxicity*
Recombination, Genetic / drug effects
Reference Values
Sister Chromatid Exchange / drug effects*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Mutagens; 33419-42-0/Etoposide; EC Topoisomerases, Type II

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