INFLUENCE OF EMF ON FREE RADICAL MEDIATED TOXOCOLOGICAL PROCESSES

EMF 对自由基介导的毒理学过程的影响

• 批准号: 2574390
• 负责人: C F CHIGNELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2574390
• 关键词: antiinflammatory agents; butylated hydroxytoluene; cytotoxicity; electromagnetic radiation; erythrocytes; free radicals; glutathione; hemolysis; magnetic field; photochemistry; radiation carcinogenesis; toxicology; triplet state; ultraviolet radiation

Although epidemiological studies suggest that there is a weak relationship between exposure to electromagnetic fields (EMF) and cancer there are at present few plausible molecular mechanisms to explain this effect. The known involvement of free radicals in the etiology of cancer and other diseases raises the possibility that EMF may somehow act by increasing the lifetime and/or concentration of free radicals. It has been known for many years that in organized media (e.g. detergent micelles) applied magnetic fields cause an increase in average free radical concentration and lengthen the lifetime of free radicals. If these effects occur in vivo then this may explain some of the reported biological effects of EMF. Our initial studies have focused on the intact erythrocyte as a test system that could be used to study the effects of MF on free radical processes. We have found that ketoprofen, a phototoxic, non-steroidal anti-inflammatory drug (structurally related to benzophenone), caused complete hemolysis of human erythrocytes after only 20 min UV irradiation. Photohemolysis was dependent on the presence of oxygen and was inhibited by reduced glutathione and butylated hydroxytoluene (BHT) suggesting that the mechanism involved lipid peroxidation. When UV irradiation was carried out in a magnetic field (3500G) the time taken for hemolysis to occur in 50% of the cells (t+) was significantly shortened (78 min vs. 96 min). A significant decrease in t1/2 could be observed at fields as low as 250G but the effect disappeared at 100G. These observations can be attributed to a magnetic field induced decrease in the rate of intersystem crossing of the geminate triplet radical pair generated by the reduction of ketoprofen in its triplet excited state by erythrocyte membrane components, probably lipids. To our knowledge this is the first demonstration of an effect of MF on a toxicological process that is known to occur via a free radical mechanism.

尽管流行病学研究表明有一种微弱的 电磁场暴露与癌症的关系 目前，几乎没有可信的分子机制来解释这一点。 效果。已知自由基在癌症病因学中的作用 而其他疾病增加了电磁场可能通过某种方式发挥作用的可能性 增加自由基的寿命和/或浓度。它有 多年来一直知道在有组织的媒体(例如洗涤剂)中 胶束)外加磁场导致平均自由态增加 能浓缩自由基，延长自由基寿命。如果 这些效应发生在体内，这可能解释了一些已报道的 电磁场的生物效应。我们的初步研究主要集中在 完整红细胞作为一种测试系统，可以用来研究 MF对自由基过程的影响。我们发现酮洛芬， 一种光毒性、非类固醇消炎药(结构相关 二苯甲酮)，引起人红细胞完全溶血 只需20分钟的紫外线照射。光溶血作用依赖于 被还原型谷胱甘肽和丁基化抑制 羟基甲苯(BHT)提示其机制与脂质有关 过氧化。当在磁场中进行紫外线照射时 (3500G)50%的细胞发生溶血所需的时间(t+) 显著缩短(78分钟比96分钟)。显著下降 在低至250g的磁场中可以观察到T1/2，但其效应 在100G时消失。这些观察结果可以归因于一种磁场 田间诱变降低了黄瓜幼虫的系统交叉率 酮洛芬还原生成的双三线态自由基对 在红细胞膜成分的三重激发状态下，可能 脂类。据我们所知，这是一种效果的第一次演示 已知的毒理过程是通过一种 激进的机制。