USE OF EPR OXIMETRY IN PATIENTS W/ TUMORS UNDERGOING RADIATION THERAPY

EPR 血氧测定法在接受放射治疗的肿瘤患者中的应用

• 批准号: 6353173
• 负责人: TED ABRAHAM
• 金额: $ 1.22万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6353173
• 关键词: Mammalia; biological products; biomaterials; biomedical resource; environmental toxicology; enzymes; hematology

Elevated levels of arsenite, the trivalent form of arsenic, in drinking water correlate with increased vascular disease and vessel remodeling. Previous studies from the laboratory demonstrated that environmentally relevant concentrations of arsenite caused oxidant-dependent increases in nuclear transcription factor levels in cultured porcine vascular endothelial cells (Barchowsky et al., Free Radical Biology & Medicine, 21:6; p.783-790, 1996). The current studies characterized the reactive species generated in these cells exposed to levels of arsenite just sufficient to signal cells. These exposures did not deplete ATP, nor did they affect basal or bradykinin-stimulated intracellular free Ca2+ levels, indicating that they were not lethal. Electron Paramagnetic Resonance (EPR) and spin trapping with carboxy-PTIO (cPTIO) demonstrated that 5 M or less of arsenite did not increase NO levels over a 30 minute time period relative to stimulation by bradykinin. However, these same levels of arsenite rapidly increase both oxygen consumption and superoxide formation, as measured by EPR oximetry and spin trapping with DMPO, respectively. Pre-treatment of the cells with diphenyleneiodonium (DPI), rotenone, or cyanide attenuated arsenite-stimulated oxygen consumption. Arsenite increased release of H2O2, measured as oxidation of homovanillic acid, with the same time and dose dependence. These data suggest that superoxide and H2O2 are the predominant reactive species produced by endothelial cells following arsenite exposures that stimulate cell signaling and activate transcription factors.

砷的水平升高，砷的三价形式 饮用水与增加的血管疾病和血管相关 重塑。 实验室的先前研究表明 砷引起的环境相关浓度 氧化剂依赖性的核转录因子水平增加 培养的猪血管内皮细胞（Barchowsky等，游离 激进生物学与医学，21：6； P.783-790，1996）。 电流 研究表征了这些细胞中产生的反应性物种 暴露于足以发出信号细胞的砷水平。 这些 暴露没有耗尽ATP，也不会影响基础或 Bradyinin刺激的细胞内无CA2+水平，表明 他们不是致命的。 电子顺磁共振（EPR）和自旋 用羧基Ptio捕获（CPTIO）表明5 m或更少 在30分钟的时间内，砷没有增加水平 相对于心动激肽刺激。 但是，这些相同的水平 砷迅速增加氧气消耗和超氧化物 形成，通过EPR血氧仪和DMPO旋转陷阱测量， 分别。 用二苯基二氧化基金的细胞预处理 （DPI），烤面包酮或氰化物减弱砷刺激的氧气 消耗。 砷增加了H2O2的释放，测量为 同时和剂量的同型氧化剂的氧化 依赖。 这些数据表明超氧化物和H2O2是 内皮细胞产生的主要反应物种之后 砷暴露于刺激细胞信号传导并激活 转录因子。