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Effects of co-exposure to extremely low frequency (50 Hz) magnetic fields and xenobiotics determined in vitro by the alkaline comet assay

机译:共暴露于碱性彗星试验在体外确定的极低频率(50 Hz)磁场和异生物的影响

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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.
机译:在本研究中,我们使用了来自4个不同供体的人外周血白细胞,以体外研究在3 mT强度下的极低频磁场(ELF-MF)可能的遗传毒性和/或协同遗传毒性活性。使用两种模型诱变剂研究ELF-MF与异种生物之间的可能相互作用: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”)分析评估初级DNA损伤。来自不同献血者的对照细胞(未暴露于ELF-MF或未经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和测试的遗传毒性化合物的敏感性导致了在存在和不存在施加的ELF-MF的情况下,暴露于基因毒素后观察到的DNA损伤程度。单独使用3 mT ELF-MF不能导致直接的初级DNA损伤。与假暴露细胞相比,在暴露于ELF-MF和基因毒素的白细胞中,MNNG诱导的DNA损伤程度随暴露时间的延长而增加。在用4NQO处理的细胞中观察到相反的情况。在这种情况下,与假暴露的细胞相比,暴露于ELF-MF的白细胞中4NQO诱导的DNA损伤的程度有所降低。此外,与假暴露的细胞相比,在暴露于ELF-MF的细胞中始终观察到GSH浓度增加。由于在GSH偶联后,MNNG和4NQO的基因毒性模式有很大不同,因此假设ELF-MF对GSH合成中涉及的酶活性的影响会导致所用模型诱变剂的激活/失活,以解释不同的原因在使用ELF-MF的情况下,MNNG和4NQO的遗传毒性活动中观察到了这种趋势。 ELF-MF可能干扰异种生物的遗传毒性活性的可能性具有重要的意义,因为人类人群可能会同时接触多种遗传毒性药物,并同时接触这类物理药物。

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