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Detection of hyperdiploidy and breakage affecting the 1cen-1q12 region of cultured interphase human lymphocytes treated with various genotoxic agents

✍ Scribed by D. S. Rupa; M. Schuler; D. A. Eastmond


Publisher
John Wiley and Sons
Year
1997
Tongue
English
Weight
85 KB
Volume
29
Category
Article
ISSN
0893-6692

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✦ Synopsis


Chromosomal aberrations are associated with can-dium arsenite and hydroquinone, agents that have cer, birth defects, and pregnancy loss. Previous been reported to have relatively weak aneuploidystudies using banding techniques have revealed inducing and clastogenic activity. Significant inthat chromosomal alterations induced in human pe-creases in chromosomal alterations were seen with ripheral lymphocytes by many genotoxic agents oc-all agents tested and the results were generally consiscur nonrandomly throughout the genome. One of tent with those previously seen using standard cytogethe regions prone to breakage is the centromeric netic techniques. Treatment with colchicine, diethylheterochromatin of chromosome 1. We have devel-stilbestrol, and vincristine sulfate resulted in high freoped a fluorescence in situ hybridization (FISH) pro-quencies of primarily hyperdiploid nuclei, and cells cedure using tandem DNA probes to distinguish hy-exposed to radiation, mitomycin C, and etoposide perdiploidy from breakage occurring in this region. exhibited elevated frequencies of breakage affecting Interphase nuclei exhibiting breakage or exchanges the 1cen-1q12 region. Sodium arsenite and hydroaffecting the 1cen-1q12 region can readily be dis-quinone induced relatively minor but significant intinguished from nuclei hyperdiploid for this chromo-creases in both hyperdiploidy and breakage. These some by identifying the number and location of the results indicate that this tandem labeling approach hybridization signals. This hybridization approach can be used to distinguish aneuploidy-inducing was tested using cultured human lymphocytes agents from those causing breakage in interphase treated with a series of known aneuploidy-inducing human cells and may be a valuable procedure for agents (colchicine, diethylstilbestrol, and vincristine monitoring human populations exposed to genotoxic sulfate), several potent clastogens (ionizing radia-agents.