Isolation and characterization of VP-16 resistant human leukemia cell line.
VP-16 resistant cells, designated VP-16K6-1 (K6-1) were isolated from human acute lymphoblastic leukemia cell line RPMI 8402. IC50 value against VP-16 were 11-fold higher than their sensitive parental cell line. The membrane permeability of the drug was not responsible for resistance in K6-1 cells. K6-1 cells showed resistance in drug-induced DNA strand breaks (single strand breaks) determined by the alkaline sucrose gradient sedimentation method. Dot-blot analysis of RNA extracted from 2 cell lines showed that the mRNA levels of DNA topoisomerase II in K6-1 cells decreased slightly compared with that of parent cells. However, Topo II activities were similar in wild-type and K6-1 cells. In addition, K6-1 cells exhibited cross-resistance only to VM-26. These data suggest that a reduced intracellular Topo II level may contribute to drug resistance as an important factor in K6-1 cells.
Hong
J H
JH
Department of Hematology, Hiroshima University, Japan.
Okada
K
K
Kusunoki
Y
Y
Komazawa
Y
Y
Kobayashi
M
M
Mizutani
A
A
Mizuno
T
T
Kuramoto
A
A
Kamada
N
N
D004261:DNA Replication; D004305:Dose-Response Relationship, Drug; D017405:Herpes Simplex Virus Protein Vmw65 / Q000302:isolation & purification*; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D013713:Teniposide / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D017405:Herpes Simplex Virus Protein Vmw65; D009943:Organophosphorus Compounds; C044965:trioctyl phosphine oxide; D013713:Teniposide