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存在较弱的 暴露于电磁场 (EMF) 与癌症之间的关系 目前几乎没有合理的分子机制来解释这一现象 影响。 已知自由基与癌症病因有关 和其他疾病提出了电磁场可能以某种方式起作用的可能性 增加自由基的寿命和/或浓度。 它有 多年来人们都知道，在有组织的介质中（例如洗涤剂 胶束）施加的磁场导致平均自由度增加 自由基浓度并延长自由基的寿命。 如果 这些效应发生在体内，那么这可以解释一些报道的情况 EMF 的生物效应。 我们最初的研究集中在 完整的红细胞作为测试系统，可用于研究 MF 对自由基过程的影响。我们发现酮洛芬， 一种光毒性、非甾体抗炎药（结构相关 为二苯甲酮），引起人红细胞完全溶血 只需20分钟的紫外线照射。光溶血取决于存在 氧并受到还原型谷胱甘肽和丁基化的抑制 羟基甲苯 (BHT) 表明该机制涉及脂质 过氧化。 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+) 显着缩短（78 分钟 vs. 96 分钟）。 显着减少 在 t1/2 中可以在低至 250G 的场中观察到，但效果 到100G就消失了。这些观察结果可归因于磁力 场引起的系统间穿越速率的降低 酮洛芬还原产生的双联三重态自由基对 由红细胞膜成分处于三重激发态，可能 脂质。 据我们所知，这是效果的首次展示 MF 对毒理学过程的影响，已知是通过自由 激进的机制。