title: Quiescence does not affect p53 and stress response by irradiation in human lung fibroblasts.
abstract: Cells in many organs exist in both proliferating and quiescent states. Proliferating cells are more radio-sensitive, DNA damage pathways including p53 pathway are activated to undergo either G1/S or G2/M arrest to avoid entering S and M phase with DNA damage. On the other hand, quiescent cells are already arrested in G0, therefore there may be fundamental difference of irradiation response between proliferating and quiescent cells, and this difference may affect their radiosensitivity. To understand these differences, proliferating and quiescent human normal lung fibroblasts were exposed to 0.10-1 Gy of γ-radiation. The response of key proteins involved in the cell cycle, cell death, and metabolism as well as histone H2AX phosphorylation were examined. Interestingly, p53 and p53 phosphorylation (Ser-15), as well as the cyclin-dependent kinase inhibitors p21 and p27, were induced similarly in both proliferating and quiescent cells after irradiation. Furthermore, the p53 protein half-life, and expression of cyclin A, cyclin E, proliferating cell nuclear antigen (PCNA), Bax, or cytochrome c expression as well as histone H2AX phosphorylation were comparable after irradiation in both phases of cells. The effect of radioprotection by a glycogen synthase kinase 3β inhibitor on p53 pathway was also similar between proliferating and quiescent cells. Our results showed that quiescence does not affect irradiation response of key proteins involved in stress and DNA damage at least in normal fibroblasts, providing a better understanding of the radiation response in quiescent cells, which is crucial for tissue repair and regeneration.
authors: Molecular Radiobiology Laboratory, Division of Cellular and Molecular Research, Singapore.
authors: Jiawen
authors: J
authors: Dai
authors: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore. Electronic address: koji.itahana@duke-nus.edu.sg.
authors: Koji
authors: K
authors: Itahana
authors: Molecular Radiobiology Laboratory, Division of Cellular and Molecular Research, Singapore; Department of Radiation Oncology, National Cancer Centre, Singapore. Electronic address: r.baskar@nccs.com.sg.
authors: Rajamanickam
authors: R
authors: Baskar
mesh_terms: D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D005720:Gamma Rays; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006207:Half-Life; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008168:Lung / Q000166:cytology*; D008301:Maleimides / Q000494:pharmacology; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D007211:Indoles; D008301:Maleimides; C417521:SB 216763; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Irradiation; Lung fibroblasts; Proliferating cells; Quiescent cells