Document Detail


Detection of hyperdiploidy and breakage affecting the 1cen-1q12 region of cultured interphase human lymphocytes treated with various genotoxic agents.
MedLine Citation:
PMID:  9118968     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chromosomal aberrations are associated with cancer, birth defects, and pregnancy loss. Previous studies using banding techniques have revealed that chromosomal alterations induced in human peripheral lymphocytes by many genotoxic agents occur nonrandomly throughout the genome. One of the regions prone to breakage is the centromeric heterochromatin of chromosome 1. We have developed a fluorescence in situ hybridization (FISH) procedure using tandem DNA probes to distinguish hyperdiploidy from breakage occurring in this region. Interphase nuclei exhibiting breakage or exchanges affecting the 1cen-1q12 region can readily be distinguished from nuclei hyperdiploid for this chromosome by identifying the number and location of the hybridization signals. This hybridization approach was tested using cultured human lymphocytes treated with a series of known aneuploidy-inducing agents (colchicine, diethylstilbestrol, and vincristine sulfate), several potent clastogens (ionizing radiation, mitomycin C, and etoposide), as well as sodium arsenite and hydroquinone, agents that have been reported to have relatively weak aneuploidy-inducing and clastogenic activity. Significant increases in chromosomal alterations were seen with all agents tested and the results were generally consistent with those previously seen using standard cytogenetic techniques. Treatment with colchicine, diethylstilbestrol, and vincristine sulfate resulted in high frequencies of primarily hyperdiploid nuclei, and cells exposed to radiation, mitomycin C, and etoposide exhibited elevated frequencies of breakage affecting the 1cen-1q12 region. Sodium arsenite and hydroquinone induced relatively minor but significant increases in both hyperdiploidy and breakage. These results indicate that this tandem labeling approach can be used to distinguish aneuploidy-inducing agents from those causing breakage in interphase human cells and may be a valuable procedure for monitoring human populations exposed to genotoxic agents.
Authors:
D S Rupa; M Schuler; D A Eastmond
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Environmental and molecular mutagenesis     Volume:  29     ISSN:  0893-6692     ISO Abbreviation:  Environ. Mol. Mutagen.     Publication Date:  1997  
Date Detail:
Created Date:  1997-04-22     Completed Date:  1997-04-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8800109     Medline TA:  Environ Mol Mutagen     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  161-7     Citation Subset:  IM    
Affiliation:
Department of Entomology, University of California, Riverside 92521, USA.
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MeSH Terms
Descriptor/Qualifier:
Aneuploidy*
Chromosomes, Human, Pair 1*
Humans
In Situ Hybridization / methods*
Lymphocytes / drug effects*
Male
Mutagens / pharmacology*
Chemical
Reg. No./Substance:
0/Mutagens

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


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