Reduced topoisomerase II-mediated DNA cleavage in VP-16 resistant human leukemic cell line.
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.
Saijo
Y
Y
Department of Internal Medicine, Tohoku University, Sendai, Japan.
Satoh
K
K
Tokue
Y
Y
Kumano
N
N
Motomiya
M
M
D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004351:Drug Resistance / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D007938:Leukemia; D010957:Plasmids
D005047:Etoposide; D004250:DNA Topoisomerases, Type II