Changes in nucleoside transport of HL-60 human promyelocytic cells during N,N-dimethylformamide induced differentiation.

Abstract

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.

• Authors: S F Chen, J S Cleaveland, A B Hollmann, M C Wiemann, R E Parks Jr, J D Stoeckler
• Journal: Cancer research (Cancer Res) Vol. 46 Issue 7 Pg. 3449-55 (Jul 1986) ISSN: 0008-5472 [Print] United States
• PMID: 3486711 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adenosine Deaminase Inhibitors
• Deoxyadenosines
• Nucleosides
• Purines
• Coformycin
• Pentostatin
• Thioinosine
• Dimethylformamide
• 4-nitrobenzylthioinosine
• Adenosine

Topics

• Adenosine (metabolism)
• Adenosine Deaminase Inhibitors
• Cell Differentiation (drug effects)
• Cell Line
• Coformycin (analogs & derivatives, metabolism)
• Deoxyadenosines (metabolism)
• Dimethylformamide (pharmacology)
• Humans
• Leukemia, Myeloid, Acute (metabolism, pathology)
• Nucleosides (metabolism)
• Pentostatin
• Purines (metabolism)
• Thioinosine (analogs & derivatives, metabolism)