Effect of verapamil on daunorubicin accumulation in human leukemic cells with different levels of MDR1 gene expression.
The purpose of the present study was to evaluate the distribution of the multiple drug resistance phenotype in leukemic cells with different levels of mdr1 gene expression. Peripheral leukemic cells from 8 patients (5 with detectable and 3 with undetectable mdr1 RNA levels) were incubated with daunorubicin (1 microM) in the absence and presence of verapamil (6.6 microM). Daunorubicin accumulation in individual cells was analysed by flow cytometry. Verapamil increased (16-45%) the mean daunorubicin accumulation in 7 of the 8 cell samples. In cells from 4 of these 7 patients, the fluorescence histograms showed a general increase of daunorubicin accumulation. The increase was limited to a small subpopulation of cells in one patient. In the remaining two patients an increase of daunorubicin accumulation was seen in the majority of cells, while cells with the highest accumulation were unaffected. In conclusion, verapamil can increase daunorubicin accumulation in leukemic cells with and without detectable mdr1 gene expression and the increase seems to affect the majority of the cell population.
Gruber
A
A
Division of Medicine, Karolinska Hospital, Stockholm, Sweden.
Briese
B
B
Areström
I
I
Vitols
S
S
Björkholm
M
M
Peterson
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003630:Daunorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*
D012334:RNA, Neoplasm; D014700:Verapamil; D003630:Daunorubicin