Queuine, a tRNA anticodon wobble base, maintains the proliferative and pluripotent potential of HL-60 cells in the presence of the differentiating agent 6-thioguanine.
6-Thioguanine (6-TG)-induced differentiation of hypoxanthine phosphoribosyltransferase (IMP: pyrophosphate phosphoribosyltransferase, EC 2.4.2.8)-deficient HL-60 cells is characterized by 2 days of growth, after which morphological differentiation proceeds. Addition of the tRNA wobble base queuine, in the presence of 6-TG, maintains the proliferative capability of the cells. The ability of 6-TG to induce differentiation correlates with c-myc mRNA down-regulation, but queuine has no effect on this parameter. Treatment with 6-TG for 2-3 days commits HL-60 cells to granulocytic differentiation, and, once committed, these cells do not respond to the monocytic inducer phorbol 12-myristate 13-acetate. Nonetheless, when cells are treated with queuine and 6-TG, they maintain the promyelocytic morphology and are capable of being induced down the monocytic pathway by phorbol 12-myristate 13-acetate as indicated by stabilization of c-fms mRNA and cell adherence. In the absence of queuine, phorbol 12-myristate 13-acetate is incapable of inducing monocytic markers in the 6-TG-treated cells. The data presented indicate that 6-TG-induced differentiation of HL-60 cells is a tRNA-facilitated event and that the tRNA wobble base queuine is capable of maintaining both the proliferative and pluripotent potential of the cells.
French
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BT
Comprehensive Cancer Center, Ohio State University, Columbus 43210.
Patrick
D E
DE
Grever
M R
MR
Trewyn
R W
RW
D000926:Anticodon / Q000235:genetics*; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D013866:Thioguanine / Q000494:pharmacology*
D000926:Anticodon; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D006147:Guanine; C019549:queuine; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine