Characterization of resistance to VP-16 in human leukemic cell line.
Resistance mechanism was studied in the VP-16-resistant human leukemic cell line (THP-1/E) which was developed by continuous drug exposure. The drug uptake and efflux studies revealed no decrease in net cellular drug accumulation. VP-16-induced DNA single- and double-strand breaks in the whole THP-1/E cells decreased significantly compared to the sensitive counterpart as assessed by alkaline elution methods. Decrease in DNA SSBs was also observable in the isolated nuclei from the THP-1/E cells. The resistance to VP-16 in THP-1/E appeared to be independent of altered membrane permeability, and more likely to be associated with decreased VP-16-mediated DNA cleavage.
Saijo
Y
Y
Department of Internal Medicine, Tohoku University, Sendai.
Kumano
N
N
Tokue
Y
Y
Satoh
K
K
Oizumi
K
K
Motomiya
M
M
D002460:Cell Line; D004273:DNA, Neoplasm / Q000187:drug effects*; D004351:Drug Resistance; D005047:Etoposide / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007938:Leukemia; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D004273:DNA, Neoplasm; D005047:Etoposide