title: Radiation-induced senescence-like terminal growth arrest in thyroid cells.
abstract: Premature senescence may play an important role as an acute, drug-, or ionizing radiation (IR)-inducible growth arrest program along with interphase apoptosis and mitotic catastrophe. The aim of the study was to evaluate whether IR can induce senescence-like phenotype (SLP) associated with terminal growth arrest in the thyroid cells, and if so, to evaluate impact of terminal growth arrest associated with SLP in intrinsic radiosensitivity of various thyroid carcinomas. The induction of SLP in thyroid cells were identified by: (1) senescence associated beta-galactosidase (SA-beta-Gal) staining method, (2) dual-flow cytometric analysis of cell proliferation and side light scatter using vital staining with PKH-2 fluorescent dye, (3) double labeling for 5-bromodeoxyuridine and SA- beta-Gal, (4) Staining for SA-beta-Gal with consequent antithyroglobulin immunohistochemistry. IR induced SLP associated with terminal growth arrest in four thyroid cancer cells lines and in primary thyrocytes in time- and dose-dependent manner. Analysis of relationship between induction of SLP and radiosensitivity revealed a trend in which more radioresistant cell lines strongly tended to show lower specific SLP yields (r = -0.93, p = 0.068). We find out that SA-beta-Gal staining is detectable in irradiated ARO xenotransplants, but not in control tumors. We, therefore, conclude that induction of SLP with terminal growth arrest contribute to the elimination of clonogenic populations after IR.
authors.affiliation: Department of Molecular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Alexei
authors.initials: A
authors.lastname: Podtcheko
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Namba
authors.forename: Vladimir
authors.initials: V
authors.lastname: Saenko
authors.forename: Akira
authors.initials: A
authors.lastname: Ohtsuru
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Starenki
authors.forename: Serik
authors.initials: S
authors.lastname: Meirmanov
authors.forename: Iryna
authors.initials: I
authors.lastname: Polona
authors.forename: Tatiana
authors.initials: T
authors.lastname: Rogounovitch
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D016922:Cellular Senescence / Q000528:radiation effects*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis; D011836:Radiation Tolerance; D013961:Thyroid Gland / Q000528:radiation effects*; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D001616:beta-Galactosidase