Melatonin and magnetic fields

There is public health concern raised by epidemiological studies indicating that extremely low frequency electric and magnetic fields generated by electric power distribution systems in the environment may be hazardous. Possible carcinogenic effects of magnetic field in combination with suggested oncostatic action of melatonin lead to the hypothesis that the primary effects of electric and magnetic fields exposure is a reduction of melatonin synthesis which, in turn, may promote cancer growth. In this review the data on the influence of magnetic fields on melatonin synthesis, both in the animals and humans, are briefly presented and discussed.     

Studies of the interactions between melatonin and 2 Hz, 0.3 mT PEMF on the proliferation and invasion of human breast cancer cells

Interactions between the hormone melatonin at pharmacological concentrations (10(-3) M) and 2 Hz, 0.3 mT pulsed electromagnetic fields (PEMF) on the proliferation and invasion of human breast cancer cells were studied in vitro. Three types of human breast cancer cells were used in this study: MDA-MB-435, MDA-MB-231, and MCF-7. Results showed that cellular growth of MDA-MB-231 cells, which were reported to be lowly metastatic, and MCF-7 cells, which were reported to be nonmetastatic, were both significantly reduced by melatonin regardless of the presence of the field. Results also showed that MDA-MB-435 and MDA-MB-231 cells were invasive, with MDA-MB-231 cells being more invasive than the MDA-MB-435 cells for both unexposed and experimental-PEMF groups. In addition, invasion studies showed that MCF-7 cells were not invasive and that melatonin did not have any effects on the invasion of these cells, with or without the PEMF. It is also suggested that since metastasis requires growth and invasion into tissue, anti-invasion agents can be used in conjunction with melatonin to prevent formation of secondary metastases. The overall studies suggest that PEMF at 2 Hz, 0.3 mT does not influence cancer metastasis; while having clinical merit in the healing of soft tissue injury, this field has shown no influence on cancer cells as 60 Hz power line fields have.     

Effects of 50 Hz magnetic fields on gap junctional intercellular communication.

To explore whether the extremely low frequency (ELF) electromagnetic fields (EMFs) may act as cancer promoters or be synergistic with 12-O-tetradecanoylphorbol-13-acetate (TPA) in cancer promotion, an experiment was conducted on the effects of 50 Hz magnetic fields (MFs) on gap junctional intercellular communication (GJIC) of Chinese hamster lung (CHL) cells. Lucifer dye was loaded into CHL cells by iontophoretic injection, and the number of dye-coupled cells (DCC) 5 min after the injection was adopted as the index of GJIC. The effects of TPA at different concentrations and magnetic fields at different intensities, combined with 5 ng/ml TPA, were studied. The results showed that the suppression of TPA on GJIC was dependent on TPA concentration; the threshold concentration of TPA for CHL cells was between 1 and 5 ng/ml. After exposure to 0.8 mT magnetic field for 24 h, the number of DCC decreased to 6.08 +/- 1.59, whereas the number of DCC in the control group was 9.84 +/- 2.27 (P < .05). When the cells were exposed at 0.2, 0.4, and 0.8 mT for 24 h, combined with 5 ng/ml TPA treatment during the last 1 h, the number of DCC decreased to 5.52 +/- 1.53, 5.00 +/- 1.22, and 4.00 +/- 1.29, respectively, which were significantly lower than the values for the group treated with 5 ng/ml TPA alone (6.38 +/- 1.39). It is suggested that certain intensities of 50 Hz magnetic field might act as cancer promoters, be additive with other promoters in cancer promotion, or both.     

Microarray gene expression profiling of a human glioblastoma cell line exposed in vitro to a 1.9 GHz pulse-modulated radiofrequency field

The widespread use of mobile phones has led to public concerns about the health effects associated with exposure to radiofrequency (RF) fields. The paramount concern of most persons relates to the potential of these fields to cause cancer. Unlike ionizing radiation, RF fields used for mobile telecommunications (800-1900 MHz) do not possess sufficient energy to directly damage DNA. Most rodent bioassay and in vitro genotoxicity/mutation studies have reported that RF fields at non-thermal levels have no direct mutagenic, genotoxic or carcinogenic effects. However, some evidence has suggested that RF fields may cause detectable postexposure changes in gene expression. Therefore, the purpose of this study was to assess the ability of exposure to a 1.9 GHz pulse-modulated RF field for 4 h at specific absorption rates (SARs) of 0.1, 1.0 and 10.0 W/kg to affect global gene expression in U87MG glioblastoma cells. We found no evidence that non-thermal RF fields can affect gene expression in cultured U87MG cells relative to the nonirradiated control groups, whereas exposure to heat shock at 43 degrees C for 1 h up-regulated a number of typical stress-responsive genes in the positive control group. Future studies will assess the effect of RF fields on other cell lines and on gene expression in the mouse brain after in vivo exposure.     

Rapporteur report: implications for exposure guidelines

There is a paucity of information regarding the long-term health effects associated with exposure to static magnetic fields. Perceptual and other acute effects have been demonstrated above a threshold of about 2 T, and these form the basis for human exposure standards at present. Exposures well above this threshold are increasingly becoming more common as the technology associated with magnetic resonance imaging advances. Therefore, priority should be given to assessing the health risks associated with exposures to such fields. Studies should include a prospective cohort study investigating cancer risks of workers and patients exposed to fields in excess of 2 T, a study investigating effects on human cognitive performance from repeated exposures, and a molecular biology study investigating acute changes in genomic responses in volunteers exposed to fields of up to 8 T. Studies investigating the effects of long-term exposure on cancer, and on neurobehavioural development are also recommended using animals, where the use of transgenic models is encouraged. In addition, dosimetric studies should be conducted using high-resolution male, female and pregnant voxel phantoms, as should theoretical studies investigating the local currents induced in the eye and in the heart by movement during exposure. Finally, studies are recommended to investigate further the ability of static magnetic fields to significantly affect radical pair reactions in biological systems.     

Low-level exposure to radiofrequency electromagnetic fields: Health effects and research needs

The World Health Organization (WHO), the International Commission on Non-Ionizing Radiation Protection (ICNIRP), and the German and Austrian Governments jointly sponsored an international seminar in November of 1996 on the biological effects of low-level radiofrequency (RF) electromagnetic fields. For purposes of this seminar, RF fields having frequencies only in the range of about 10 MHz to 300 GHz were considered. This is one of a series of scientific review seminars held under the International Electromagnetic Field (EMF) Project to identify any health hazards from EMF exposure. The scientific literature was reviewed during the seminar and expert working groups formed to provide a status report on possible health effects from exposure to low-level RF fields and identify gaps in knowledge requiring more research to improve health risk assessments. It was concluded that, although hazards from exposure to high-level (thermal) RF fields were established, no known health hazards were associated with exposure to RF sources emitting fields too low to cause a significant temperature rise in tissue. Biological effects from low-level RF exposure were identified needing replication and further study. These included in vitro studies of cell kinetics and proliferation effects, effects on genes, signal transduction effects and alterations in membrane structure and function, and biophysical and biochemical mechanisms for RF field effects. In vivo studies should focus on the potential for cancer promotion, co-promotion and progression, as well as possible synergistic, genotoxic, immunological, and carcinogenic effects associated with chronic low-level RF exposure. Research is needed to determine whether low-level RF exposure causes DNA damage or influences central nervous system function, melatonin synthesis, permeability of the blood brain barrier (BBB), or reaction to neurotropic drugs. Reported RF-induced changes to eye structure and function should also be investigated. Epidemiological studies should investigate: the use of mobile telephones with hand-held antennae and incidence of various cancers; reports of headache, sleep disturbance, and other subjective effects that may arise from proximity to RF emitters, and laboratory studies should be conducted on people reporting these effects; cohorts with high occupational RF exposure for changes in cancer incidence; adverse pregnancy outcomes in various highly RF exposed occupational groups; and ocular pathologies in mobile telephone users and in highly RF exposed occupational groups. Studies of populations with residential exposure from point sources, such as broadcasting transmitters or mobile telephone base stations have caused widespread health concerns among the public, even though RF exposures are very low. Recent studies that may indicate an increased incidence of cancer in exposed populations should be investigated further. Bioelectromagnetics 19:1–19, 1998. © 1998 Wiley-Liss, Inc.     

No effects of extremely low frequency magnetic fields found on cytotoxic activities and cytokine production of human peripheral blood mononuclear cells in vitro

Several epidemiologic studies have suggested an association between exposure to extremely low frequency (ELF) magnetic fields (MFs) and cancer in adults and children. A possible target of MFs is the immune system. The effects of the exposure to ELF MFs on the immunological functions of human peripheral blood mononuclear cells (PBMCs) obtained from healthy male volunteers were assessed by measuring the natural killer (NK) and lymphokine activated killer (LAK) activities and the production of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and interleukin-10 (IL-10). The PBMCs were exposed to three different MF: linearly polarized (vertical), circularly polarized, and elliptically polarized, at 50 and 60 Hz. Magnetic flux densities were set at 500, 100, 20, and 2 microT (rms) for vertical field and at 500 microT (rms) for the rotating fields. Using cytotoxicity assay and enzyme-linked immunosorbent assay (ELISA) for cytokine production, we could not find any effects of ELF MFs on the cytotoxic activities and the cytokines production of human PBMCs.     

Absence of genotoxicity in human blood cells exposed to 50 Hz magnetic fields as assessed by comet assay, chromosome aberration, micronucleus, and sister chromatid exchange analyses

In the past, epidemiological studies indicated a possible correlation between the exposure to ELF fields and cancer. Public concern over possible hazards associated with exposure to extremely low frequency magnetic fields (ELFMFs) stimulated an increased scientific research effort. More recent research and laboratory studies, however, have not been able to definitively confirm the correlation suggested by epidemiological studies. The aim of this study was to evaluate the effects of 50 Hz magnetic fields in human blood cells exposed in vitro, using several methodological approaches for the detection of genotoxicity. Whole blood samples obtained from five donors were exposed for 2 h to 50 Hz, 1 mT uniform magnetic field generated by a Helmholtz coil system. Comet assay, sister chromatid exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN) tests were used to assess DNA damage, one hallmark of malignant cell transformation. The effects of a combined exposure with X-rays were also evaluated. Results obtained do not show any significant difference between ELFMFs exposed and unexposed samples. Moreover, no synergistic effect with ionizing radiation has been observed. A slight but significant decrease of cell proliferation was evident in ELFMFs treated samples and samples subjected to the combined exposure.     

Extremely low frequency electric fields and cancer: Assessing the evidence

Much of the research and reviews on extremely low frequency (ELF) electric and magnetic fields (EMFs) have focused on magnetic rather than electric fields. Some have considered such focus to be inappropriate and have argued that electric fields should be part of both epidemiologic and laboratory work. This paper fills the gap by systematically and critically reviewing electric‐fields literature and by comparing overall strength of evidence for electric versus magnetic fields. The review of possible mechanisms does not provide any specific basis for focusing on electric fields. While laboratory studies of electric fields are few, they do not indicate that electric fields should be the exposure of interest. The existing epidemiology on residential electric‐field exposures and appliance use does not support the conclusion of adverse health effects from electric‐field exposure. Workers in close proximity to high‐voltage transmission lines or substation equipment can be exposed to high electric fields. While there are sporadic reports of increase in cancer in some occupational studies, these are inconsistent and fraught with methodologic problems. Overall, there seems little basis to suppose there might be a risk for electric fields, and, in contrast to magnetic fields, and with a possible exception of occupational epidemiology, there seems little basis for continued research into electric fields. Bioelectromagnetics 31:89–101, 2010. © 2009 Wiley‐Liss, Inc.     

Transient suppression of X-ray-induced apoptosis by exposure to power frequency magnetic fields in MCF-7 cells

Epidemiological studies suggest that exposure to power frequency magnetic fields may be a risk factor for breast cancer in humans. To study the relationship between exposure to 60-Hz magnetic fields (MFs) and breast cancer, cell cycle distribution, apoptosis, and the expression of related proteins (p21, Bax, and Bcl-2) were determined in MCF-7 cells following exposure to magnetic fields (60 Hz, 5 mT) alone or in combination with X rays. It was found that exposure of MCF-7 cells to 60-Hz MFs for 4, 8, and 24 h had no effect on cell cycle distribution. Furthermore, 60-Hz MFs failed to affect cell growth arrest and p21 expression induced by X rays (4 Gy). Similarly, 60-Hz MFs did not induce apoptosis or the expression of Bax and Bcl-2, two proteins related to apoptosis. However, exposure of cells to 60-Hz MFs for 24 h after irradiation by X rays (12 Gy) significantly decreased apoptosis and Bax expression but increased Bcl-2 expression. The effects of exposure to 60-Hz MFs on X-ray-induced apoptosis and Bax and Bcl-2 expressions were not observed at 72 h. These data suggest that exposure to 60-Hz MFs has no effects on the growth of MCF-7 cells, but it might transiently suppress X-ray-induced apoptosis through increasing the Bcl-2/Bax ratio.     

Health effects of static magnetic fields--a review of the epidemiological evidence

Potential health effects of static magnetic fields have received far less attention than, for example, power frequency or radiofrequency fields. Static fields are found in certain occupational settings, e.g. in the aluminium and chloralkali industries, in arc-welding processes, and certain railways systems. Magnetic resonance imaging (MRI) for medical diagnosis is another source. This paper summarizes the epidemiological evidence of static magnetic field exposure and long-term health effects. There are only a few epidemiological studies available, and the majority of these have focused on cancer risks. There are some reports on reproductive outcomes, and sporadic studies of other outcomes. Overall, few occupational studies have focused specifically on effects of static magnetic field exposure, and exposure assessment have consequently been poor or non-existent. Results from studies that have estimated static magnetic field exposure have not indicated any increased cancer risks, but they are generally based on small numbers of cases and crude exposure assessment. Control of confounding has been limited, and it is likely that the “healthy worker” effect have influenced the results. A few studies have reported results on reproductive outcomes among aluminium workers and MRI operators, but limitations in study designs prevent conclusions. A problem in epidemiological studies of static magnetic fields is that workers in exposed occupations are also exposed to a wide variety of other potentially harmful agents, including some known carcinogens. In conclusion, the available evidence from epidemiological studies is not sufficient to draw any conclusions about potential health effects of static magnetic field exposure.     

稻鸭共育生态效应及经济效益

稻鸭共育是一项无须使用除草剂和施用较少农药的低成本生态农业技术。通常,20d左右大的鸭子按225只.hm-2放入移栽不久的稻田。由于取食和活动,它们能够帮助控制田间杂草、虫害、甚至病害,并且对水稻生长发育、土壤理化性状、水体溶氧量和微生物等产生一定的影响。本文概述了稻鸭共育的生态效应和经济效益的研究进展,并指出应加强在精确施肥和水稻后期病虫害防治等方面的深入研究。     

Static magnetic fields: animal studies

Various experimental studies carried out over the last 30–40 years have examined the effects of the chronic or acute exposure of laboratory animals to static magnetic fields. Many of the earlier studies have been adequately reviewed elsewhere; few adverse effects were identified. This review focuses on studies carried out more recently, mostly those using vertebrates, particularly mammals. Four main areas of investigation have been covered, viz., nervous system and behavioural studies, cardiovascular system responses, reproduction and development, and genotoxicity and cancer. Work on the role of the natural geomagnetic field in animal orientation and migration has been omitted.

Generally, the acute responses found during exposure to static fields above about 4 T are consistent with those found in volunteer studies, namely the induction of flow potentials around the heart and the development of aversive/avoidance behaviour resulting from body movement in such fields. No consistently demonstrable effects of exposure to fields of 1 T and above have been seen on other behavioural or cardiovascular endpoints. In addition, no adverse effects of such fields on reproduction and development or on the growth and development of tumours have been firmly established. Overall, however, far too few animal studies have been carried out to reach any firm conclusions.     

Effects of static magnetic fields at the cellular level

There have been few studies on the effects of static magnetic fields at the cellular level, compared to those of extremely low frequency magnetic fields. Past studies have shown that a static magnetic field alone does not have a lethal effect on the basic properties of cell growth and survival under normal culture conditions, regardless of the magnetic density. Most but not all studies have also suggested that a static magnetic field has no effect on changes in cell growth rate. It has also been shown that cell cycle distribution is not influenced by extremely strong static magnetic fields (up to a maximum of 10 T). A further area of interest is whether static magnetic fields cause DNA damage, which can be evaluated by determination of the frequency of micronucleus formation. The presence or absence of such micronuclei can confirm whether a particular treatment damages cellular DNA. This method has been used to confirm that a static magnetic field alone has no such effect. However, the frequency of micronucleus formation increases significantly when certain treatments (e.g., X-irradiation) are given prior to exposure to a 10 T static magnetic field. It has also been reported that treatment with trace amounts of ferrous ions in the cell culture medium and exposure to a static magnetic field increases DNA damage, which is detected using the comet assay. In addition, many studies have found a strong magnetic field that can induce orientation phenomena in cell culture.     

Does lack of tocopherols and tocotrienols put women at increased risk of breast cancer?

Breast cancer is the leading site of new cancers in women and the second leading cause (after lung cancer) of cancer mortality in women. Observational studies that have collected data for dietary exposure to alpha-tocopherol with or without the other related tocopherols and tocotrienols have suggested that vitamin E from dietary sources may provide women with modest protection from breast cancer. However, there is no evidence that vitamin E supplements confer any protection whatever against breast cancer. Observational studies that have assessed exposure to vitamin E by plasma or adipose tissue concentrations of alpha-tocopherol have failed to provide consistent support for the idea that alpha-tocopherol provides any protection against breast cancer. In addition, evidence from studies in experimental animals suggest that alpha-tocopherol supplementation alone has little effect on mammary tumors. In contrast, studies in breast cancer cells indicate that alpha- gamma-, and delta-tocotrienol, and to a lesser extent delta-tocopherol, have potent antiproliferative and proapoptotic effects that would be expected to reduce risk of breast cancer. Many vegetable sources of alpha-tocopherol also contain other tocopherols or tocotrienols. Thus, it seems plausible that the modest protection from breast cancer associated with dietary vitamin E may be due to the effects of the other tocopherols and the tocotrienols in the diet. Additional studies will be required to determine whether this may be the case, and to identify the most active tocopherol/tocotrienol.     

Association of residential magnetic fields with contact voltage

The US National Electrical Code's (NEC) requirement to ground a home's electrical service to the residential water line results in a voltage between the water line and earth, V W-E. The voltage may result from ground return current that flows into the earth via the water line or from inductive effects from other sources of magnetic fields, such as transmission lines. This voltage can, in turn, serve as a source for Vbath, the voltage between the water fixtures and conductive drain pipes sunk into the earth beneath a residence. Vbath can be a source of contact current exposure to a child touching a water fixture while bathing. Previous research has suggested that exposure to these currents could be the basis for the association between power-frequency magnetic fields and childhood leukemia. In this study, we assessed the association between measured Vbath and VW-E with the average spot-measured magnetic field, Bavg, in a sample of 191 single-family residences in the Denver metropolitan area. This area was the source of cases and controls for previous studies of electric and magnetic field (EMF) and childhood cancer. The association of both Vbath and VW-E with Bavg had upward trends across magnetic field strata (<0.1 microT (reference); 0.1-<0.3 microT; and > or = 0.3 microT). In addition, VW-E was associated with Vbath. Without further study, these results cannot be applied to multi-dwelling residences or to electrical systems prevalent in other nations. Nonetheless, when combined with the finding that contact current is a far more plausible candidate than the residential magnetic field for mediating biological effects on the basis of comparative dose to bone marrow, these associations indicate that contact current exposure deserves further study.     

Mechanism of action of moderate-intensity static magnetic fields on biological systems

There is substantial evidence indicating that moderate-intensity static magnetic fields (SMF) are capable of influencing a number of biological systems, particularly those whose function is closely linked to the properties of membrane channels. Most of the reported moderate SMF effects may be explained on the basis of alterations in membrane calcium ion flux. The mechanism suggested to explain these effects is based on the diamagnetic anisitropic properties of membrane phospholipids. It is proposed that reorientation of these molecules during moderate SMF exposure will result in the deformation of imbedded ion channels, thereby altering their activation kinetics. Channel inactivation would not be expected to be influenced by these fields because this mechanism is not located within the intramembraneous portion of the channel. Patch-clamp studies of calcium channels have provided support for this hypothesis, as well as demonstrating a temperature dependency that is understandable on the basis of the membrane thermotropic phase transition. Additional studies have demonstrated that sodium channels are similarly affected by SMFs, although to a lesser degree. These findings support the view that moderate SMF effects on biological membranes represent a general phenomenon, with some channels being more susceptible than others to membrane deformation.     

Magnetic fields and the melatonin hypothesis: a study of workers chronically exposed to 50-Hz magnetic fields

Because epidemiological studies report clinical disorders (mainly neurobehavioral alterations and/or cancer) that may be related to diminished melatonin secretion or to changes in its circadian rhythm in subjects living or working in environments exposed to magnetic fields, research on the effects of these fields in humans is particularly important. In this study, we examine the circadian rhythm of melatonin in 15 men exposed chronically and daily for a period of 1-20 yr, in the workplace and at home, to a 50-Hz magnetic field in search of any cumulative effect from those chronic conditions of exposure. The weekly geometric mean of individual exposures ranged from 0.1 to 2.6 microT. The results are compared with those for 15 unexposed men who served as controls (individual exposures ranged from 0.004 to 0.092 microT). Blood samples were taken hourly from 2000 to 0800. Nighttime urine was also collected and analyzed. This work shows that subjects exposed over a long period (up to 20 yr) and on a daily basis to magnetic fields experienced no changes in their plasma melatonin level, their urinary 6-sulfatoxymelatonin level, or the circadian rhythm of melatonin. Our data strongly suggest that magnetic fields do not have cumulative effects on melatonin secretion in humans and thus clearly rebut the "melatonin hypothesis" that a decrease in plasma melatonin concentration (or a disruption in its secretion) explains the occurrence of clinical disorders or cancers possibly related to magnetic fields.     

Prostate cancer with variants in CYP17 and UGT2B17 genes: a meta-analysis

Both CYP17 and UGT2B17 are suggested to be potential risk factors of prostate cancer (PCa). To date, many studies have evaluated the relationship between CYP17 T-34C and UGT2B17 Del polymorphisms and Prostate cancer with conflicting results. Here, we performed comprehensive meta-analyses of over 25 studies, including results from about 17,000 subjects on the association of CYP17 T-34C and UGT2B17 Del polymorphisms with Prostate cancer. Overall, no significant associations between CYP17 T-34C polymorphism and Prostate cancer risk were found for T versus C (P=0.63), TT versus CC (P=0.52), TT+TC versus CC (P=0.40) or TT versus TC+CC (P=0.98), though there was a marginally significant association with the UGT2B17 Del polymorphism under Del/Del versus Ins/Ins +Ins/Del (P=0.05). In an analysis of various subgroups, there were no substantially significant associations with the CYP17 T-34C polymorphism; while there was a significant association for the UGT2B17 Del/Del genotype in a subgroup of men-based controls (P < 0.0001). The current meta-analysis results suggest that the CYP17 T-34C polymorphism may not be associated with Prostate cancer, while the UGT2B17 Del polymorphism may significantly contribute to prostate cancer susceptibility in men. These findings also support the idea that CYP17 has no significant effects on androgen levels, while UGT2B17 does.     

Methodologic considerations for trials of lung cancer prophylaxis.

Prophylaxis is likely to be of increasing importance in the control of lung cancer. Areas already suggested as potential fields of investigation include the use of specific immunoprophylaxis or synthetic retinoids. Thorough evaluation of the effects and hazards of such prophylaxis will be required, and the most satisfactory approach is to conduct controlled prophylactic trials. Such trials must rest on the same basic principles as those established for therapeutic trials. However, new problems bearing on ethical requirements, the sampling procedure, and the practical conduct of the trials will arise. Compliance, adverse effects, end points for analysis of the prophylactic effects, and rules for when to stop a trial are discussed.