title: Induction of granulocytic maturation in HL-60 human leukemia cells by free radicals: a hypothesis of cell differentiation involving hydroxyl radicals.
abstract: Tumor cells usually contain lower superoxide dismutase (SOD) activity than differentiating cells, suggesting the involvement of oxygen free radicals in cell maturation. The effects of a system known to produce the OH. radicals were tested on HL-60 cells cultured under optimum conditions for 96 hr. Hydroxyl radicals were generated by a Fenton reaction, involving an ADP-Fe2+ (or ATP-Fe2+) complex and H2O2. Changes induced by OH. were compared to the effects of DMSO-induced differentiation of HL-60 cells. Cell numbers, viability, thymidine incorporation, TPA-induced NBT reduction and propidium iodide staining in flow cytometry were determined. The OH. generating system inhibited the growth and thymidine incorporation of leukemic cells in a manner dependent on the dose of added H2O2 (from 0.005 to 0.05 mM). In addition, an increasing proportion of the treated cells displayed signs of cell differentiation. In DMSO-treated cells, SOD and catalase activities increased after 6 days of culturing. The results show that a portion of the OH. free radicals derived from H2O2, produced by the action of SOD, may be a necessary prerequisite for differentiation, whereas an overproduction of OH. causes cell lethality or aging. We suggest that OH. free radicals may have a more complex role in cell physiology than simply causing oxidative damage.
authors.affiliation: Verzár International Laboratory for Experimental Gerontology (VILEG), Debrecen, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Nagy
authors.forename: G
authors.initials: G
authors.lastname: Pásti
authors.forename: L
authors.initials: L
authors.lastname: Bene
authors.forename: I
authors.initials: I
authors.lastname: Zs-Nagy
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D006098:Granulocytes / Q000166:cytology* / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008954:Models, Biological; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: C045076:Fenton's reagent; D005609:Free Radicals; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine; D004121:Dimethyl Sulfoxide