Đang chuẩn bị liên kết để tải về tài liệu:
Báo cáo khoa học: " A specific inhibitor of protein kinase CK2 delays gamma-H2Ax foci removal and reduces clonogenic survival of irradiated mammalian cells"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Radiation Oncology cung cấp cho các bạn kiến thức về ngành y đề tài: A specific inhibitor of protein kinase CK2 delays gamma-H2Ax foci removal and reduces clonogenic survival of irradiated mammalian cells. | Zwicker et al. Radiation Oncology 2011 6 15 http www.ro-journal.eom content 6 1 15 RADIATION ONCOLOGY RESEARCH Open Access A specific inhibitor of protein kinase CK2 delays gamma-H2Ax foci removal and reduces clonogenic survival of irradiated mammalian cells 1.2 1 1.2 1 1 Felix Zwicker Maren Ebert Peter E Huber Jurgen Debus Klaus-Josef Weber Abstract Background The protein kinase CK2 sustains multiple pro-survival functions in cellular DNA damage response and its level is tightly regulated in normal cells but elevated in cancers. Because CK2 is thus considered as potential therapeutic target DNA double-strand break DSB formation and rejoining apoptosis induction and clonogenic survival was assessed in irradiated mammalian cells upon chemical inhibition of CK2. Methods MRC5 human fibroblasts and WIDR human colon carcinoma cells were incubated with highly specific CK2 inhibitor 4 5 6 7-tetrabromobenzotriazole TBB or mock-treated 2 hours prior to irradiation. DSB was measured by pulsed-field electrophoresis PFGE as well as gamma-H2AX foci formation and removal. Apoptosis induction was tested by DAPI staining and sub-G1 flow cytometry survival was quantified by clonogenic assay. Results TBB treatment did not affect initial DNA fragmention PFGE up to 80 Gy or foci formation 1 Gy . While DNA fragment rejoining PFGE was not inhibited by the drug TBB clearly delayed gamma-H2AX foci disappearence during postirradiation incubation. No apoptosis induction could be detected for up to 38 hours for both cell lines and exposure conditions monotherapies or combination but TBB treatment at this moderately toxic concentration of 20 dM about 40 survival enhanced radiation-induced cell killing in the clonogenic assay. Conclusions The data imply a role of CK2 in gamma-H2AX dephosporylation most likely through its known ability to stimulate PP2A phosphatase rather than DSB rejoining. The slight but definite clonogenic radiosensitization by TBB does apparently not result from .