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: 6162244
• 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/6162244
• 关键词: antiinflammatory agents; butylated hydroxytoluene; cytotoxicity; electromagnetic radiation; erythrocytes; free radicals; glutathione; hemolysis; magnetic field; photochemistry; radiation carcinogenesis; tissue /cell culture; toxicology; triplet state; ultraviolet radiation

Summary of Work: 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. We have now found that,in the absence of an applied external magnetic field, polystyrene microspheres containing magnetite (Fe3O4) also dramatically increase the rate of photohemolysis. This effect was not observed when control microspheres (ie no Fe3O4) or soluble iron (FeCl3) were present These observations suggest that the magnetic field associated with the spheres is responsible for the increase in the rate of hemolysis. Our findings 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 these are the first demonstrations of an effect of MF on a toxicological process(hemolysis) that is known to occur via a free radical mechanism.

工作总结：尽管流行病学研究表明， 暴露于电磁场 (EMF) 和 癌症目前尚无合理的分子机制 解释一下这个效应。 已知自由基参与 癌症和其他疾病的病因学提出了电磁场可能 以某种方式通过增加游离态的寿命和/或浓度来起作用 部首。多年来，众所周知，在有组织的媒体中（例如 洗涤剂胶束）施加的磁场导致平均 自由基集中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。我们现在发现，在没有应用的情况下 外部磁场，含磁铁矿的聚苯乙烯微球 (Fe3O4) 也显着增加光溶血的速率。这 当对照微球（即没有 Fe3O4）或 存在可溶性铁 (FeCl3) 这些观察结果表明 与球体相关的磁场负责 溶血率增加。 我们的发现可以归因于 磁场导致系间穿越速率下降 通过还原生成的双三重态自由基对 酮洛芬通过红细胞膜处于三重激发态 成分，可能是脂质。 据我们所知，这些是第一个 证明 MF 对毒理学过程（溶血）的影响 已知这是通过自由基机制发生的。