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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adenocarcinoma, Apoptosis, Ataxia Telangiectasia Mutated Proteins, Blotting, Western, Cell Cycle, Cell Cycle Proteins, Cell Proliferation, Chromatin Immunoprecipitation, Combined Modality Therapy, Comet Assay, DNA Damage, DNA, Neoplasm, DNA-Activated Protein Kinase, DNA-Binding Proteins, Female, Flow Cytometry, Humans, Immunoenzyme Techniques, Mammary Neoplasms, Experimental, Nuclear Proteins, Protein-Serine-Threonine Kinases, Quinoxalines, Radiation, Ionizing, Radiation-Sensitizing Agents, Reactive Oxygen Species, Tumor Cells, Cultured, Tumor Suppressor Proteins.
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Does the radiosensitizer 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide induce DNA damage in EMT-6 mammary carcinoma cells? Context: DCQ (2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide), a synthetic quinoxaline 1,4-dioxide, enhances the cytotoxic effect of ionizing radiation (IR) in vivo and in vitro. We sought to clarify whether increased radiation-induced DNA damage, decreased rate of damage repair, and the generation of reactive oxygen species (ROS) contribute to DCQ enhancement of IR. Murine mammary adenocarcinoma EMT-6 cells were treated with DCQ for 4 h before exposure to 10 Gy IR. Treated cells were monitored for modulations in cell cycle, induction of DNA damage, and generation of ROS. Combined DCQ and IR treatments (DCQ+IR) induced rapid cell-cycle arrests in EMT-6 cells, particularly in S and G2/M phases. Alkaline comet assays revealed high levels of DNA damage in cells after exposure to DCQ+IR, consistent with damage-induced arrest. Unlike IR-only and DCQ-only treated cells, the damage induced by combined DCQ+IR was repaired at a slower rate. Combined treatment, compared to separate DCQ and IR treatments, activated DNA-protein kinase and induced more p-ATM, supporting a role for double strand breaks (DSBs), which are more toxic and difficult to repair than single strand breaks (SSBs). Contributing factors to DCQ radiosensitization appear to be the induction of ROS and DSBs.
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Collectively, our findings indicate that radiosensitization by DCQ is mediated by DNA damage and decreased repair and that ROS are at least partially responsible. Final Decision: yes