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.

亚砷酸盐（砷的三价形式）含量升高 饮用水与血管疾病和血管疾病增加相关 重塑。 实验室之前的研究表明 造成的亚砷酸盐环境相关浓度 核转录因子水平的氧化剂依赖性增加 培养的猪血管内皮细胞（Barchowsky 等人，免费 激进生物学与医学，21:6；第 783-790 页，1996 年）。 目前的 研究表征了这些细胞中产生的活性物质 暴露于足以向细胞发出信号的亚砷酸盐水平。 这些 暴露不会消耗 ATP，也不会影响基础或 缓激肽刺激的细胞内游离 Ca2+ 水平，表明 它们并不致命。 电子顺磁共振 (EPR) 和自旋 用羧基-PTIO (cPTIO) 捕获表明 5 M 或更少 亚砷酸盐在 30 分钟内不会增加 NO 水平 与缓激肽的刺激有关。 然而，这些相同水平的 亚砷酸盐迅速增加耗氧量和超氧化物 通过 EPR 血氧测定法和 DMPO 自旋捕获测量形成， 分别。 用二亚苯基碘鎓预处理细胞 (DPI)、鱼藤酮或氰化物衰减亚砷酸盐刺激氧 消耗。 亚砷酸盐增加了 H2O2 的释放，测量为 高香草酸的氧化，相同的时间和剂量 依赖性。 这些数据表明超氧化物和 H2O2 是 内皮细胞产生的主要活性物质如下 亚砷酸盐暴露会刺激细胞信号传导并激活 转录因子。