title: Senescence-like changes induced by hydroxyurea in human diploid fibroblasts.
abstract: Hydroxyurea was found to inhibit the growth of human diploid fibroblasts, which resulted in senescence-like changes both in morphology and replicative potential similar to the replicative senescence. SA-beta-gal activity, a typical characteristic of the replicative senescence was also induced through a long-term treatment of the presenescent cells with 400-800 microgM of hydroxyurea for about 3 weeks. In addition, we determined the levels of cyclin-dependent kinase inhibitors, p21(Waf1) and p16(INK4a), and the p53 tumor suppressor in order to monitor its effect on cell cycle and stress responses. We observed a great induction of both p53 and p21(Waf1), but not of p16(INK4a) in the premature senescent cells. UV-irradiation of the premature senescent cells showed a decreased level of DNA fragmentation presumably ascribed to the reduced activation of stress-activated protein kinases. These results suggest that a chronic hydroxyurea treatment induces the cellular senescence in association with the induction of p53 and p21(Waf1).
authors.affiliation: Department of Biochemistry, Cheju National University Colege of Medicine, Cheju, South Korea.
authors.forename: E J
authors.initials: EJ
authors.lastname: Yeo
authors.forename: Y C
authors.initials: YC
authors.lastname: Hwang
authors.forename: C M
authors.initials: CM
authors.lastname: Kang
authors.forename: I H
authors.initials: IH
authors.lastname: Kim
authors.forename: D I
authors.initials: DI
authors.lastname: Kim
authors.forename: J S
authors.initials: JS
authors.lastname: Parka
authors.forename: H E
authors.initials: HE
authors.lastname: Choy
authors.forename: W Y
authors.initials: WY
authors.lastname: Park
authors.forename: S C
authors.initials: SC
authors.lastname: Park
mesh_terms: D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D053938:DNA Fragmentation; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000633:toxicity*; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: C493956:CDKN1A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D006918:Hydroxyurea