RESUMO
The ataxia telangiectasia-mutated (ATM) protein, which is mutated in the inherited disease ataxia telangiectasia (AT), is a key activator of cell cycle checkpoint, initiating cell response to DNA damage and ensuring genomic stability. AT cells exhibit defects in all cellular responses to ionizing radiation and radiomimetic chemicals. Inactivation of ATM may therefore make cells fail to execute many responses to DNA damage and improve the cells' sensitivity to radiation. Recent developments in the use of small interference RNA molecules (siRNAs) to inhibit specific protein expression have highlighted the potential use of siRNA as a therapeutic agent. In this study, we have designed and exogenously delivered plasmids encoding siRNAs targeting ATM to human cervical carcinoma SiHa cells and generated a stable cell line, SiHa(ATM). SiHa(ATM) cells displayed minimal levels of ATM protein and showed a marked increase in sensitivity to radiation. Together, these data provide strong evidence for the potential use of siRNA as a novel radiation/chemotherapy-sensitizing agent.
Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Sobrevivência Celular/efeitos da radiação , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , RNA Interferente Pequeno/farmacologia , Tolerância a Radiação/fisiologia , Proteínas Supressoras de Tumor/antagonistas & inibidores , Neoplasias do Colo do Útero/patologia , Ataxia Telangiectasia/metabolismo , Ataxia Telangiectasia/patologia , Proteínas Mutadas de Ataxia Telangiectasia , Western Blotting , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta à Radiação , Feminino , Citometria de Fluxo , Humanos , Fosforilação/efeitos da radiação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Radiação Ionizante , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Neoplasias do Colo do Útero/genéticaRESUMO
Because deuteron-induced reactions on 51V, 52Cr, 56Fe, and 57Fe have been widely used in medical radioisotope production, research on radiation damage, and activation analysis, the excitation functions were evaluated and calculated for 51V, 52Cr, 56Fe, and 57Fe (d, n), (d, p), (d, alpha), (d, 3He), (d, d'), (d, t), (d, 2n), (d, np + pn), (d, nalpha + alphan), (d, 2p) and (d, 3n) from respective threshold to 30.0 MeV.