Document Detail


AZT induces high frequency, rapid amplification of centromeric DNA.
MedLine Citation:
PMID:  9186505     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The reverse transcriptase inhibitor 3'-azido-deoxythymidine (AZT) has previously been shown to be incorporated into specific regions near the telomeres and centromeres of Chinese hamster ovary cell chromosomes. Our investigation of the effects of AZT on chromosome stability has led to the discovery of a high frequency amplification of telomere-like centromeric DNA. The amplified structures, when analyzed cytogenetically, appear as tandem arrays of tightly clustered blocks of centromeric repeats containing telomeric sequences (TTAGGG)n. There were 5-13 blocks of amplified DNA per structure. These structures form rapidly within one or two cell cycles and can be observed with an incidence as high as 2%. Because the amplification was so rapid, we tested whether the amplification structures could be the result of aberrant overreplication by analyzing BrdU incorporation. Our results indicate that the amplified DNA does not undergo abnormal replication during its formation, but appears to form from existing centromeric regions. We propose a model that involves the excision of multiple centromeric DNA regions from other chromosomes and their relocalization to a new site.
Authors:
I Parra; C Flores; D Adrian; B Windle
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cytogenetics and cell genetics     Volume:  76     ISSN:  0301-0171     ISO Abbreviation:  Cytogenet. Cell Genet.     Publication Date:  1997  
Date Detail:
Created Date:  1997-07-08     Completed Date:  1997-07-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0367735     Medline TA:  Cytogenet Cell Genet     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  128-33     Citation Subset:  IM; X    
Affiliation:
Cancer Therapy and Research Center, San Antonio, TX 78229, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimetabolites / pharmacokinetics
Bromodeoxyuridine / pharmacology
CHO Cells
Centromere / drug effects
Cricetinae
DNA / drug effects*
Dose-Response Relationship, Drug
Gene Amplification
Reverse Transcriptase Inhibitors / pharmacology*
Telomere
Zidovudine / pharmacology*
Grant Support
ID/Acronym/Agency:
CA54785/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antimetabolites; 0/Reverse Transcriptase Inhibitors; 30516-87-1/Zidovudine; 59-14-3/Bromodeoxyuridine; 9007-49-2/DNA

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


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