Effect of deferoxamine on DNA synthesis, DNA repair, cell proliferation, and differentiation of HL-60 cells.
The ribonucleotide reductase inhibitors deferoxamine and hydroxyurea induce monocyte-macrophage cell differentiation in the leukemic cell line HL-60 as judged by the expression of cell surface antigens, nonspecific esterase activity, and morphological changes. Treatment of HL-60 cells with deferoxamine results in inhibition of DNA synthesis and irreversible loss of colony-forming ability. In addition, both deferoxamine and hydroxyurea caused an increase in the number of DNA strand breaks in HL-60 cells. A DNA methylating agent, N-methyl-N'-nitro-N-nitrosoguanidine, also caused cellular differentiation in HL-60 cells associated with DNA strand breaks. These observations are consistent with a role for DNA damage or for inhibition of DNA synthesis and repair in the differentiation process of HL-60 cells.
Kaplinsky
C
C
Division of Immunology/Rheumatology, Hospital for Sick Children, Toronto, Ontario, Canada.
Estrov
Z
Z
Freedman
M H
MH
Gelfand
E W
EW
Cohen
A
A
D000954:Antigens, Surface / Q000032:analysis; D001549:Benzamides / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D003676:Deferoxamine / Q000494:pharmacology*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D001549:Benzamides; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D008769:Methylnitronitrosoguanidine; C025160:3-aminobenzamide; D012264:Ribonucleotide Reductases; D003676:Deferoxamine; D006918:Hydroxyurea