Changes in nucleoside transport of HL-60 human promyelocytic cells during N,N-dimethylformamide induced differentiation.
The rate of nucleoside transport decreased profoundly in human promyelocytic leukemia HL-60 cells after myeloid differentiation was induced by 5-6 days of exposure to 0.8% N,N-dimethylformamide (DMF). The facilitated diffusion of 100 microM radiolabeled adenosine and 2'-deoxyadenosine, measured by rapid transport assays, decreased 10- to 20-fold. The transport of 2 microM coformycin or 2'-deoxycoformycin, which is mediated by the same mechanism and was monitored by the adenosine deaminase titration assay, decreased 29-fold. The reduction in nucleoside transport capacity after DMF treatment was confirmed by a 19-fold decrease in the number of specific binding sites per cell (from 24-30 X 10(4) to 1.2-1.7 X 10(4)) for [3H]-6-p-nitrobenzylthioinosine, a nucleoside transport inhibitor. The binding affinity of 6-p-nitrobenzylthioinosine was not altered significantly and nucleoside transport remained sensitive to the transport inhibitors, 6-p-nitrobenzylthioinosine, dipyridamole, and dilazep after DMF-induced maturation. Time-dependence studies showed that the rate of 100 microM deoxyadenosine transport was unchanged for the first 24 h of exposure to DMF but fell to about 36% of control rates at 24-26 h and then gradually decreased further to about 4-5% of control rates after 5-6 days. In contrast, transport rates of the purine bases were reduced only 2- to 3-fold in HL-60 cells after 5 days of DMF treatment. The rates of adenosine and deoxyadenosine transport were unchanged or reduced by no more than 2-fold after 5-6 days of exposure to 0.8% DMF in the following human tumor cell lines that are not inducible with DMF: ARH-77 (multiple myeloma), KG-1 (acute myelogenous), and K-562 (chronic myelogenous). Thus, changes in nucleoside transport may serve as an early, membrane-associated marker of differentiation of the HL-60 cell line.
D000241:Adenosine / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003070:Coformycin / Q000031:analogs & derivatives / Q000378:metabolism; D003839:Deoxyadenosines / Q000378:metabolism; D004126:Dimethylformamide / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D009705:Nucleosides / Q000378:metabolism*; D015649:Pentostatin; D011687:Purines / Q000378:metabolism; D013868:Thioinosine / Q000031:analogs & derivatives / Q000378:metabolism
D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D009705:Nucleosides; D011687:Purines; D003070:Coformycin; D015649:Pentostatin; D013868:Thioinosine; D004126:Dimethylformamide; C001789:4-nitrobenzylthioinosine; D000241:Adenosine