Prevention of 1-beta-D arabinofuranosylcytosine toxicity by 4-nitrobenzyl-6-thioinosine or dipyridamole in human leukemia cell lines.
The ability of the nucleoside transport inhibitors, 4-nitrobenzyl-6-thioinosine (NBTI) and dipyridamole (DP) to prevent 1-beta-D arabinofuranosylcytosine (Ara-C) toxicity was evaluated in two human leukemia cell lines, Molt 4 and HL-60. At non-toxic concentrations, DP (in Molt4 and HL-60) and NBTI (only in Molt 4) provided significant protection, whereas HL-60 was quite insensitive to NBTI. The different response of these two cell lines to NBTI and DP was also noted in the toxicity of other nucleoside analogs, including 9-beta-D arabinofuranosyladenine (Ara-A), 2'-chlorodeoxyadenosine (CdA), tubercidin and 5'-bromodeoxyuridne (BUdR). A transport study of [3H]-Ara-C revealed that NBTI partially inhibited the drug entry into HL-60 cells, which correlated well with Ara-CTP generation.
Kubota
M
M
Department of Pediatrics, Kyoto University, Japan.
Takimoto
T
T
Kitoh
T
T
Tanizawa
A
A
Kiriyama
Y
Y
Akiyama
Y
Y
Mikawa
H
H
D001085:Arabinofuranosylcytosine Triphosphate / Q000096:biosynthesis; D001692:Biological Transport / Q000187:drug effects; D003561:Cytarabine / Q000378:metabolism* / Q000633:toxicity; D003864:Depression, Chemical; D004176:Dipyridamole / Q000494:pharmacology*; D004351:Drug Resistance; D006801:Humans; D007288:Inosine / Q000031:analogs & derivatives*; D007945:Leukemia, Lymphoid / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008297:Male; D008727:Methotrexate / Q000378:metabolism / Q000633:toxicity; D009705:Nucleosides / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011355:Prodrugs / Q000378:metabolism* / Q000633:toxicity; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013936:Thymidine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D009705:Nucleosides; D004364:Pharmaceutical Preparations; D011355:Prodrugs; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate; D013868:Thioinosine; D007288:Inosine; D004176:Dipyridamole; C001789:4-nitrobenzylthioinosine; D013936:Thymidine; D008727:Methotrexate