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Changes in Nucleoside Transport of HL-60 Human Promyelocytic Cells during N,N-Dimethylformamide Induced Differentiation¹

Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912 [S-F. C., J. S. C., R. E. P., J. D. S.] and Department of Medicine, Roger Williams General Hospital, Providence, Rhode Island 02908 [A. B. H., M. C. W.]

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 µM radiolabeled adenosine and 2'-deoxyadenosine, measured by rapid transport assays, decreased 10- to 20-fold. The transport of 2 µM 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 29-fold decrease in the number of specific binding sites per cell (from 24–30 x 10⁴ to 1.2–1.7 x 10⁴) 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 µM 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.

¹ This work was supported by USPHS grants CA 37901, 20892, and 13943 awarded by the National Cancer Institute, Department of Health and Human Services. This report is a publication of the Roger Williams Cancer Center.

² Present address: Biomedical Products Department, Glenolden Laboratory, Du Pont Company, 500 S. Ridgeway Avenue, Glenolden, PA 19036.

³ To whom requests for reprints should be addressed.

Received 10/25/85. Revised 2/25/86. Accepted 3/25/86.

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