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KMID : 0352819950100020009
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Kosin Medical Journal
1995 Volume.10 No. 2 p.9 ~ p.16
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Effects of benzo(a)pyrene on the DNA topoisomerase II-mediated DNA cleavage in
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Abstract
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In a previous study, we have found that benzo(a)pyrene(BP) and it's metabolites specificaily bind to the DNA topoitomerase II traction of mouse fibroblast C3H/10T1/2 cell cultures. The enzyme was predicted to be a primary target of BP causing
malignancy. We theretore investigated, in the present study, changes in DNA cleavage by various concentrations of BP bound to DNA topoisomerase II in the human c-myc protooncogene. DNA topoisomerase II was purified by glycerol gradient
centrifugation
from murine L1210 leukemia cells. Supercoiled pBR322 DNA was completely reversed to a relaxed form in the presence of 160ng of purified DNA topoisomerase II. In BP-treated HindIII/XbaI cutting c-myc DNA, DNA cleavage was most apparently increased
in the
upstream of exon 1, the effect being particularly pronounced with 0.1 M BP. It is indicated that stimulation of the DNA topoisomerase II induced DNA cleavage sites in the c-myc by BP act on selective region, which increased cleavage at specific
sites
may induce gene expression of abnormal pattern.
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KEYWORD
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