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The Clinical and Fundamental Study of Free Radicals Produced by Anticancer Drugs and Function of Blood Cells

抗癌药物产生的自由基与血细胞功能的临床和基础研究

基本信息

批准号：
62570889
负责人：
KIMURA Hiroto
金额：
$ 1.28万
依托单位：
Hirosaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

项目摘要

As the method to detect free radicals, I have applied the CLA - dependent chemiluminescence specific to superoxide anion radical ( O^-_ and the ESR spin trapping technique highly sensitive to hydroxyl radical ( ・OH ) by this Grant-in-Aid.1. The Effects of Anticancer Drugs on the Active Oxygen Produced by Polymorphnuclear Leukocyte(PEN). The production of O^-_ from PMN stimulated by OZ or PMA was remarkably enhanced by the addition of BLM and its analog, Peplomycin (PEP). The effect of PEP is stronger than that of BLM. Any other anticancer drugs did not influence on the generation of O^-_ from PMN. The method to measure O^-_ is CLA -dependent chemi-luminescence using luminescence reader purchased by this Grant-in-Aid.2. Clinical Study of the Active Oxygen Production by PMN from Oral Cancer Patients. The O^-_ production ability of PMN obtained from patients showed low values compared to that of PMN from healthy volunteers. The administration of anticancer drugs to the patients had no effect on the O^-_ production ability of PMN from the patients except for PMA as a stimulant. These results suggested that the primary host-defence mechanism of patients were depressed. The investigation of the changes for long periods must be the subject of further study.3. Effect of Anticancer Drugs on Free Radical Generation Systems in vitro. I report here the effect of BLM and PEP on free radical generation systems, which were (1)HX+XOD -> O^-_ and (2)Fe(II)+H_2O_2-> ・OH, using chemiluminescence method and ESR spin trapping technique. As results, both BLM and PEP increased the free radical generation in proportion to the concentration of drugs. The effect of PEP is two times stronger than that of BLM same as described above.These results suggested that the Fe(II) - BLM complex reacted with free radicals to produce secondarily hydroxyl radicals.

作为检测自由基的方法，我应用了超氧阴离子自由基(O^-_)的共轭亚油酸依赖的化学发光和对羟基自由基(·OH)高度敏感的ESR自旋捕获技术。抗癌药物对多形核白细胞(PEN)产生活性氧的影响加入博莱曼及其类似物培普霉素(PEP)可显著促进OZ或PMA刺激的PMN产生O^-__。PEP的作用强于BLM。其他抗癌药物对中性粒细胞产生O^-_无影响。本实验所采用的测量O^-__的方法是基于共轭亚油酸的化学发光，使用的是本公司购买的发光读数。口腔癌患者外周血多形核细胞产生活性氧的临床研究患者PMN的O^-产生能力低于健康志愿者PMN。患者给予抗癌药物治疗后，除PMA作为刺激剂外，对PMN产生O^--能力无明显影响。这些结果表明，患者的主要宿主防御机制受到抑制。对长期变化的调查必须是进一步研究的主题。抗癌药物对体外自由基生成系统的影响本文用化学发光法和ESR自旋捕捉技术研究了BLM和PEP对(1)HX+XOD-&GT；O^-_和(2)Fe(II)+H_2O_2-&GT；·OH自由基生成体系的影响。结果表明，BLM和PEP均随药物浓度的增加而增加自由基的产生。PEP的作用比BLM强一倍以上，上述结果表明，Fe(II)-BLM络合物与自由基反应产生二次羟基自由基。