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.