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Drug resistance in the VP-16 resistant human leukemic cell line (THP-1/E) was studied the possible relevance of topoisomerase II activity. Strand-passing activity in crude nuclear extract from sensitive and resistant cells was comparable and equally sensitive to inhibition by VP-16. However, it was demonstrated that VP-16-mediated pBR322 DNA cleavage in the presence of nuclear extract from resistant cells was reduced to one-tenth of that from sensitive cells. These results suggested that the resistance of THP-1/E cells to VP-16 was due to reduced DNA cleavage activity.
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