RADIOPROTECTANT COPPER COMPLEX--CU-LL-3,5-DIPS-2

辐射防护铜络合物--CU-LL-3,5-DIPS-2

• 批准号: 3180234
• 负责人: John Robert Joseph Sorenson
• 金额: $ 9.65万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-30 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3180234
• 关键词: antibody specificity; chemical hypersensitivity; chemical synthesis; copper; gamma radiation; ionizing radiation; metal complex; radiation immunosuppression; radiation recovery; radiation sensitivity; radiopharmacology; radioprotective agents; tissue /cell culture

Long term objectives are to evaluate Bis 3,5-diisopropylsaliclatocopper (II) Cu(II)(3,5-dips)2 treatment regimens for radioprotection of cells grown in culture and mice irradiated with clinically relevant doses of X- and gamma-radiation (40-170 rads/minute to deliver 800 to 1000 rads), and evaluate effects of radiation and treatment (0, 60, 80, or 100 mg/kg) on essential metalloelement metabolism and immunocompetency of mice. Specific aims of this proposal are to synthesize sufficient quantities of Cu(II) (3,5-dips)2 to enable studies of its radioprotectant activity. Radioprotectant activity will be determined by measuring survival of irradiated cultured cells and whole-body irradiated mice. Survival and treatment regimen will be correlated for irradiated cells grown in culture. Altered essential metalloelement metabolism and immunocompetency will be determined for irradiated and treated mice. Survival, alteration of plasma, liver, spleen, intestine, brain, and bone marrow copper content as well as immunocompetency will be correlated for irradiated and treated mice. Routine synthetic procedures will be used to synthesize Cu(II)(3,5-dips)2. Atomic absorption spectrophotometric methods will be used to determine tissue copper content. Colony formation, as measured with Puck-Marcus single cell techniques, will be used to determine irradiated-cell survival. Survival will also be used to measure the in vivo radioprotectant activity. Immunocompetency will be determined by evaluating the abilities of different lymphocyte subclasses to repopulate hosts with determinations of spleen cell markers, mitogen responsiveness, and bone marrow colony forming units. Antibody responsiveness will be measured using the Jerne plaque-forming assay and determinations of cell-mediated immunity will be measured using oxazolone hypersensitivity and mixed lymphocyte reactivity. Appropriate statistical programs will be used to evaluate significance of differences found in these studies.

长期目标是评估双3，5-二异丙基水杨酸铜 (2)铜(II)(3，5-二苯基)2治疗方案，用于细胞的辐射防护 在培养中生长，并经临床相关剂量的X-射线照射的小鼠 和伽马辐射(40-170拉德/分钟，发射800-1000拉德)，以及 评估放射和治疗(0、60、80或100 mg/kg)对 小鼠的必需金属元素代谢和免疫能力。 这项提议的具体目标是合成足够数量的 铜(II)(3，5-二苯基)2，使研究其辐射防护活性成为可能。 辐射防护剂的活性将通过测量 照射培养的细胞和全身照射的小鼠。生存和发展 治疗方案将与生长在 文化。必需金属元素代谢改变与免疫功能 将对受过辐射和治疗的小鼠进行检测。生存，改变 血浆、肝、脾、肠、脑和骨髓铜含量 以及免疫能力将与辐射和治疗相关 老鼠。 将使用常规的合成步骤来合成Cu(II)(3，5-dips)2。 将使用原子吸收分光光度法来测定 组织铜含量。用Puck-Marcus法测量的菌落形成 单细胞技术，将被用来确定辐照细胞 生死存亡。存活率也将被用来测量体内的 辐射防护剂的活性。免疫能力将由以下因素决定 评价不同淋巴细胞亚群的再生能力 宿主的脾细胞标志物，有丝分裂原反应性， 和骨髓集落形成单位。抗体反应性将是 用杰恩斑块形成试验测量和测定 将使用恶唑酮超敏反应来测量细胞介导的免疫 混合淋巴细胞反应性。适当的统计方案将是 用于评估在这些研究中发现的差异的意义。