Villarini Milena, Moretti Massimo, Scassellati-Sforzolini Giuseppina, Boccioli Bruno, Pasquini Rossana
Department of Medical-Surgical Specialities and Public Health, University of Perugia, Via del Giochetto, 06126 Perugia, Italy.
Sci Total Environ. 2006 May 15;361(1-3):208-19. doi: 10.1016/j.scitotenv.2005.05.006. Epub 2005 Jun 24.
In the present study, we used human peripheral blood leukocytes from 4 different donors, to investigate in vitro the possible genotoxic and/or co-genotoxic activity of extremely low frequency magnetic fields (ELF-MF) at 3 mT intensity. Two model mutagens were used to study the possible interaction between ELF-MF and xenobiotics: N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline N-oxide (4NQO). Primary DNA damage was evaluated by the alkaline single-cell microgel-electrophoresis ("comet") assay. Control cells (leukocytes not exposed to ELF-MF, nor treated with genotoxins) from the different blood donors showed a comparable level of basal DNA damage, whereas the contribution of individual susceptibility toward ELF-MF and the tested genotoxic compounds led to differences in the extent of DNA damage observed following exposure to the genotoxins, both in the presence and in the absence of an applied ELF-MF. A 3 mT ELF-MF alone was unable to cause direct primary DNA damage. In leukocytes exposed to ELF-MF and genotoxins, the extent of MNNG-induced DNA damage increased with exposure duration compared to sham-exposed cells. The opposite was observed in cells treated with 4NQO. In this case the extent of 4NQO-induced DNA damage was somewhat reduced in leukocytes exposed to ELF-MF compared to sham-exposed cells. Moreover, in cells exposed to ELF-MF an increased concentration of GSH was always observed, compared to sham-exposed cells. Since following GSH conjugation the genotoxic pattern of MNNG and 4NQO is quite different, an influence of ELF-MF on the activity of the enzyme involved in the synthesis of GSH leading to different activation/deactivation of the model mutagens used was hypothesized to explain the different trends observed in MNNG and 4NQO genotoxic activity in the presence of an applied ELF-MF. The possibility that ELF-MF might interfere with the genotoxic activity of xenobiotics has important implications, since human populations are likely to be exposed to a variety of genotoxic agents concomitantly with exposure to this type of physical agent.
在本研究中，我们使用了来自4名不同捐赠者的人类外周血白细胞，以体外研究3 mT强度的极低频磁场（ELF-MF）可能具有的遗传毒性和/或协同遗传毒性活性。使用两种模型诱变剂来研究ELF-MF与异生物素之间可能的相互作用：N-甲基-N'-硝基-N-亚硝基胍（MNNG）和4-硝基喹啉-N-氧化物（4NQO）。通过碱性单细胞微凝胶电泳（“彗星”）试验评估原发性DNA损伤。来自不同献血者的对照细胞（未暴露于ELF-MF且未用基因毒素处理的白细胞）显示出相当水平的基础DNA损伤，而个体对ELF-MF和测试的基因毒性化合物的易感性导致在暴露于基因毒素后观察到的DNA损伤程度存在差异，无论是否施加ELF-MF。单独的3 mT ELF-MF无法引起直接的原发性DNA损伤。在暴露于ELF-MF和基因毒素的白细胞中，与假暴露细胞相比，MNNG诱导的DNA损伤程度随暴露时间增加。在用4NQO处理的细胞中观察到相反的情况。在这种情况下，与假暴露细胞相比，暴露于ELF-MF的白细胞中4NQO诱导的DNA损伤程度有所降低。此外，与假暴露细胞相比，在暴露于ELF-MF的细胞中总是观察到谷胱甘肽（GSH）浓度增加。由于在GSH结合后MNNG和4NQO的遗传毒性模式有很大不同，因此推测ELF-MF对参与GSH合成的酶活性的影响导致所使用的模型诱变剂的不同激活/失活，以解释在施加ELF-MF的情况下在MNNG和4NQO遗传毒性活性中观察到的不同趋势。ELF-MF可能干扰异生物素的遗传毒性活性这一可能性具有重要意义，因为人类群体在暴露于这种物理因素的同时可能会接触到多种遗传毒性剂。
