Effects of 60 Hz extremely low frequency magnetic fields (EMF) on radiation- and chemical-induced mutagenesis in mammalian cells
Raheel M. Ansari and
Tom K. Hei1
Center for Radiological Research, College of Physicians and Surgeons of Columbia University, VC 11-218, 630 West 168th Street, New York, NY 10032, USA
 |
Abstract
|
---|
There is considerable uncertainty of the potential biological effects of extremely low frequency magnetic fields (ELF-MF or EMF) because of mixed results in epidemiological and laboratory studies. In the present study, exponentially growing humanhamster hybrid AL cells were treated with a 100 µT alternating EMF powered at 60 Hz for either 24 h or 7 days. Exposure to EMF was conducted either alone or in combination with graded doses of a physical or chemical carcinogen.
-radiation was chosen as a form of ionizing radiation while N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was chosen as a form of chemical contaminant. Exposure of AL cells to EMF alone for a period up to 7 days was non-cytotoxic and non-mutagenic. Concurrent EMF treatment did not increase either the cytotoxicity or induction of CD59 mutants by graded doses of
-rays or MNNG in AL cells. This study shows conclusively that short-term or long-term exposure to EMF alone neither affects the survival of AL cells nor increases the mutagenic potency of other environmental carcinogens.
Abbreviations: ELF-MF (or EMF), extremely low frequency magnetic fields; MNNG, N-methyl-N'-nitro-N-nitrosoguanidine.
 |
Introduction
|
---|
It has been well established that all electrical devices generate weak electric and magnetic fields into the surrounding environment (1). Since these fields are of low frequency (ranging from 50 to 60 Hz), it has been assumed for decades that they are harmless to human health. However, epidemiology studies in the past 10 years have raised the possibility that there may be a direct correlation between alternating extremely low frequency magnetic field (ELF-MF or EMF) exposure and cancer induction. It should be noted that this body of evidence is only suggestive of a causal link and is far from definitive.
The association between cancer induction in humans and exposure to EMF (5060 Hz) was first suggested based on epidemiological findings of an excess leukemia incidence among children living in the vicinity of high tension wires (2). Subsequent epidemiological studies by others conducted in several different countries provide supporting evidence linking EMF to a variety of human malignancies including brain tumors and leukemia (35). Whereas few of the early epidemiological studies demonstrate unequivocally the association between exposure to EMF and cancer, the consistency of the marginal findings over time heightens concern by the general public and demands definitive answers from regulatory agencies.
Although investigations such as these early epidemiology studies suggest a possible association between residential exposure to 60 Hz EMF and childhood leukemia, they have an important limitation: actual magnetic fields within the home were not measured, instead `wire codes' were generally used as a surrogate for magnetic fields (6). Furthermore, the association of residential EMF exposure and risk of cancer induction is not consistent across epidemiology studies. Although a number of residential studies have reported an increase in risk of childhood leukemia, several other investigations have showed no positive correlation (79).
Occupational EMF exposure has also heightened concern due to the fact that such exposure indices are much greater than residential exposure, and because of the growing population of exposed individuals. Like the residential investigations, many epidemiology studies focused on electrical occupations have suggested a possible link between EMF exposure and the risk of several forms of acute myeloid and chronic lymphocytic leukemia as well as breast cancer (1013). At the same time, several cohort studies focused on similar electrical occupations demonstrated no such correlation (1416). Moreover, assessment of exposure across occupational epidemiology studies is limited by the manner of EMF exposure classification: EMF exposures are often classified by job titles instead of measured exposure values.
Tobacco and radon have been proven in laboratory studies to be carcinogenic (1719), providing direct laboratory evidence to support epidemiological data. In contrast, EMF by itself has not been shown to induce tumors in laboratory animals (20). There is recent evidence to suggest that alternating EMF has weak promotional effects in both the two-stage skin tumor model using SENCAR mice (21) and in rat mammary tumors (22). However, studies on in vitro oncogenic transformations induced or promoted by EMF are limited and few of those reported have used conditions comparable with the extremely low frequency regions likely to be encountered in residential or occupational settings (23).
Although EMF has never been shown to be mutagenic by itself, there is evidence to suggest that it may act as a co-mutagen. Studies have shown that EMF (50 Hz) enhanced X-ray-induced gene mutations at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus by 12-fold in Chinese hamster ovary cells (24) and by 3-fold in human melanoma cells (25). Although the mechanism for this co-mutagenic effect is not known, these data are in agreement with the promotional effects observed in the in vivo studies described above. However, studies on the co-mutagenic effects of a 1.1 Tesla (T) magnetic field in conjunction with a 3.3 Gy dose of X-rays on recessive mutation incidence among Drosophila melanogaster showed no difference in mutagenic potential with or without concurrent magnetic field treatment (26). Unfortunately, all of these studies are limited in scope involving only a single dose of X-rays, thus making a definitive conclusion hard to draw.
Several factors such as differences in research design and the inability to replicate experiments have impeded a clear interpretation of laboratory studies investigating the biological effects of EMF (23). Results have been inconsistent across different exposure indices within and across studies (3,9,27) and discrepant with respect to the cancer types putatively affected (10,11,28). Due to the inevitable exposure to EMF for a massive population base, a more consistent database obtained with well-defined exposure conditions is urgently needed for a better understanding of the potential adverse health effects. Therefore, it would be ideal to use a highly sensitive mutational assay system, a standardized EMF exposure device, and a suitable dose of EMF exposure that is relevant to today's industrial surroundings to assess the mutagenic and co-mutagenic effects of EMF in conjunction with both physical and chemical carcinogens.
In this study, the short- and long-term biological effects of a 100µT (1 gauss) alternating magnetic field powered at 60 Hz are examined because this field strength is most relevant to residential and some occupational exposure levels. The mutagenic potential of EMF either alone or in combination with
-radiation or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is examined using the human-hamster hybrid AL cell line. This mutagenic assay is preferable over other more conventional systems such as Ouabain and HPRT because of its ability to not only detect mutations at the gene level, but at the chromosomal level as well. The greatest advantage of the use of a sensitive in vitro mutagenic assay such as that of the AL cell assay is in low-dose risk assessment where genotoxic endpoints can be directly measured as opposed to relying on extrapolation from high-dose data.
 |
Materials and methods
|
---|
Cell culture
The humanhamster hybrid (AL) cells developed by Waldren and Puck (30,31) that contain a standard set of Chinese hamster ovary-K1 chromosome and a single copy of human chromosome 11 were used. Chromosome 11 contains the CD59 gene (formerly known as M1C1) at 11p13.5, which encodes the CD59 cell surface antigen (also known as the S1 antigen). Wild-type AL cells lyse in the presence of specific complement and antiserum against the CD59 antigen (E7.1), while mutated cells that have lost the CD59 gene and, therefore, the cell surface marker, survive to form colonies (30). Antibody E7.1 was produced from hybridoma cultures as described (32) and rabbit serum was used as a source of complement. Cells were routinely maintained in exponential growth phase in Ham's F12 medium supplemented with 8% heat-inactivated fetal bovine serum (Atlanta Biologicals, Norcross, AT), 2x normal glycine (2x104 M) and 25 µg/ml gentamycin as described (32,33).
EMF exposure system
The MC-2XC concentric coil in vitro exposure system (Columbia Magnetic Incorporation, Kennewick, WA) which meets all the current magnetic field system design requirements of the US National Institute of Environmental Health Sciences was used in this study (Figure 1
). The system was powered at 5060 Hz by a variable transformer and utilizes two Merritt 4-coil sets arranged in a concentric configuration to limit stray fields. Two exposure chambers were connected to a Forma Scientific incubator (model 3026) that was held remote to prevent interference with the exposure study and to provide temperature and humidity to the exposure chambers. One exposure chamber was designated for sham exposure and the system contained an active compensation device to cancel weak circulating magnetic fields while equal currents flow in both exposed and sham coils to provide identical exposure conditions (but magnetic fields were absent in the sham chamber). The temperature difference between the two chambers was within ±0.1°C with magnetic field uniformity better than ±5%.

View larger version (42K):
[in this window]
[in a new window]
|
Fig. 1. Schematic diagram of the MC-2XC in vitro system showing coil configuration, commercial incubator and remote exposure chambers.
|
|
Irradiation
Exponential phase cultures of AL cells were plated in 60 mm diameter tissue culture dishes at a density of 105 cells/dish 2 days before treatment.
-rays from a 137Cesium irradiator at an absorbed dose rate of 1.01 Gy/min provided low-linear energy transfer radiation. In each of the 12 independent experiments performed, six dishes were irradiated with either a 1.5 or 3 Gy dose of
-rays. After irradiation, two irradiated dishes were placed in a normal incubator as irradiated controls while the other four dishes, two per set, were placed in the EMF exposure and sham chambers. Equivalent numbers of non-irradiated dishes were used either as the control or placed, in sets of two each, in the EMF exposure and sham chambers. The control culture was trypsinized and replated for survival and mutational assays. After 24 h and 7 days of EMF exposure at a constant 100 µT dose, the appropriate groups were trypsinized and replated for both surviving and mutation fraction as described (3335). During the 7 days of EMF exposure, groups were subcultured once to maintain exponential growth.
Chemical exposure
Exponential-phase cultures of AL cells plated two days before treatment, as described above, were treated with graded doses of MNNG for 24 h. Cells were then washed twice with Hank's balanced salt solution and fresh medium was replaced. As described above, dishes were then placed in their respective EMF or sham exposure chamber, or normal incubator for the required treatment period and processed as described.
Survival assay
At the conclusion of the various treatment periods, cultures were washed with buffered salt solution, trypsinized, counted with a Coulter counter (Coulter Corporation, Miami, FL) and replated in 100 mm diameter tissue culture dishes at a density such that 6080 viable clones would survive the treatment (typically ranging from 100 to 400 cells per dish). Cultures were incubated for 710 days at which time they were fixed with buffered formalin, stained with Giemsa and the number of colonies was counted.
Mutation assay
After completion of the EMF and sham treatments, cultures were trypsinized, replated and incubated for 1 week before mutagenesis testing began as described (3335). This expression period is necessary in order to permit surviving cells to recover from the temporary growth lag caused by the various treatments and to multiply sufficiently so that the progeny of the mutant cells are no longer expressing lethal amounts of the CD59 surface antigen. Maximum expression of mutants occurs 714 days after mutagen treatment and remains fairly constant for several weeks before leveling off. Cell cultures to be tested were trypsinized and counted, and aliquots containing 5x104 cells were plated into each of five 60 mm diameter plastic dishes in a total of 2 ml of F12 medium. The dishes were incubated for 2 h to allow cell attachment to the surface, after which 0.2% CD59 antiserum and 1.5% freshly thawed complement were added to each dish as described previously (3235). Controls included identical sets of dishes with appropriate numbers of cells containing antiserum alone, complement alone or neither agent. Cell cultures were tested each week for 2 consecutive weeks to ensure the full expression of mutants. Seven to 10 days after plating, cells were fixed with buffered formalin, stained with Giemsa stain and surviving colonies were counted. Mutation frequencies were determined as the number of surviving colonies over the total number of cells plated after correction for any non-specific cell killing due to complement alone.
Statistical analysis
Statistical analysis of data was carried out using Student's two-tailed t-test for unpaired data. Differences between means were regarded as significant if P < 0.05.
 |
Results
|
---|
The normal plating efficiency of AL cells ranged from 73 to 89% for the 12 experiments monitoring the survival rate of cells exposed to graded doses or
-radiation with or without concurrent EMF treatment for either 24 h or 7 days (Figures 2 and 3
). EMF treatment by itself, whether for 24 h (lane 5) or 7 days (lane 10), was non-cytotoxic to AL cells and the survival data were comparable with the appropriate sham-exposure (lanes 6 and 11) and control. Although a slight increase in survival rate was detected in AL cells treated with either EMF or sham exposure, such an increase was not statistically significant from the control (P > 0.05). Exposure of AL cultures to
-rays induced a dose-dependent reduction in survival in the 24 h group. Irradiation with a 1.5 and 3 Gy dose of
-rays resulted in surviving fractions of 0.56 and 0.32 respectively. Concurrent exposure to a 100 µT EMF for 24 h (lane 3 in Figures 2 and 3
) did not modulate the radiosensitivity of the AL cultures. Consistent with previously documented studies, delayed plating after radiation exposure increased the surviving fraction in both the 1.5 and 3 Gy dose group subcultured 7 days post-irradiation. Similarly, concurrent exposure to a 100 µT EMF for 7 days resulted in no modulation of the radiation survival of the irradiated cell population (Figures 2 and 3
).

View larger version (74K):
[in this window]
[in a new window]
|
Fig. 2. Effects of a 100 µT EMF on survival fractions of AL cells treated with or without a 1.5 Gy dose of -rays. Exponentially growing cells were replated into 60 mm tissue culture dishes at 1x105 cells per dish. Forty-eight hours later, the cultures were first irradiated, and then treated with EMF (+) or sham exposed (-) for the designated treatment period. Data were pooled from three to six experiments. Bars show ±SD.
|
|
Data for the induction of CD59- mutants by graded doses of
-radiation and EMF, either alone or in combination are shown in Figures 4 and 5
. The background mutant fraction of AL cells used in these experiments averaged 78.9 ± 33.4 mutants per 105 survivors. A 24 h and 7 day treatment with EMF exposure or sham alone induced a low and insignificant mutant fraction relative to the background frequency.
-rays induced a dose-dependent increase in CD59- mutants in AL cells. A 3 Gy dose exposure resulted in an induced mutant fraction (total number of mutants minus background) that was ~3-fold above the background when subcultured 24 h after irradiation (Figure 5
). Further holding of the irradiated population induced a decrease in mutagenic yield such that continuous culture of irradiated cells 7 days post-radiation treatment reduced the mutant fraction to ~50% of the 24h group (lane 7 versus lane 2 in Figures 4 and 5
). Concurrent exposure to a 100 µT dose of EMF for either a 24 h or 7 day period did not alter the mutant fractions induced by radiation treatment alone. It can be established from these results that short- or long-term EMF exposure alone has no effects on either the clonogenic viability of AL cells or the co-mutagenic potential with
-rays.

View larger version (38K):
[in this window]
[in a new window]
|
Fig. 4. Mutation induction at the CD59- locus in AL cells treated with a 1.5 Gy dose of -rays and a 100µT EMF (+) or sham exposure (-). Results were expressed as number of induced mutants (total mutant yield minus background) per 105 survivors. Data were pooled from three to six experiments. Bars show ±SD.
|
|

View larger version (48K):
[in this window]
[in a new window]
|
Fig. 5. Mutation induction at the CD59- locus in AL cells treated with a 3 Gy dose of -rays and a 100 µT EMF (+) or sham exposure (-). Results were expressed as number of induced mutants (total mutant yield minus background) per 105 survivors. Data were pooled from three to six experiments. Bars show ±SD.
|
|
N-nitroso compounds are metabolites formed from N-nitrosation in human upon ingestion of nitrite-preserved food, from herbicide contamination and smoking (18,29). In laboratory studies MNNG has been shown to be a direct alkylating agent that does not require metabolic activation. To assess the co-mutagenicity of a chemical carcinogen with EMF, two doses of MNNG corresponding to low and moderate cytotoxicity were chosen in the present study. Figure 6
shows the surviving fraction of AL cells exposed to the higher dose of 0.05 µg/ml MNNG, either alone or in combination with a 100 µT dose of EMF for either a 24 h or 7 day exposure. Treatment of AL cells with EMF alone was non-toxic and non-mutagenic (data not shown). Whereas MNNG treatment showed a dose-dependent increase in toxicity (low-dose data not shown), with the higher dose at 0.05 µg/ml resulting in ~50% cell killing, there was no modulation of chemically induced toxicity by concurrent exposure to EMF for up to 7 days.

View larger version (60K):
[in this window]
[in a new window]
|
Fig. 6. Effects of a 100 µT EMF on survival fractions of AL cells treated in combination with a 0.05 µg/ml dose of MNNG. Exponentially growing cells were replated into 60 mm tissue culture dishes at 1x105 cells per dish. Forty-eight hours later, the cultures were treated with MNNG for 24 h, and then treated with EMF (+) or sham exposed (-) for the proper treatment period. Data were pooled from three to five experiments. Bars show ±SD.
|
|
In addition, MNNG induced a dose-dependent increase in CD59- mutants in AL cells with the 0.05 µg/ml dose exposure, resulting in an induced mutant fraction that was ~2 fold above the background incidence of 66.3 ± 33.7 per 105 survivors when subcultured 24 h post-treatment (Figure 7
). Holding of the chemically exposed cultures induced a further decrease in mutagenic yield such that continuous cultivation of MNNG-treated cells for 7 days reduced the mutant fraction to ~40% of the 24 h group. Furthermore, concurrent exposure to a 100 µT EMF for either a 24 h or 7 day period did not alter the mutant fraction induced by MNNG treatment alone.

View larger version (59K):
[in this window]
[in a new window]
|
Fig. 7. Effects of a 100 µT EMF (+) or sham exposure (-) on induction of CD59- mutants in AL cells treated with a 0.05 µg/ml dose of MNNG for 24 h. Induced mutant frequency is the total mutant yield minus background. Data were pooled from three to five experiments. Bars show ±SD.
|
|
 |
Discussion
|
---|
Electromagnetic fields are widely present in today's industrial society and expose an enormous population. The discrepancies in many of the epidemiology and laboratory studies have heightened concern of the general public and demand definitive assessment of exposure risk from regulatory agencies. Various in vitro and in vivo studies have shown that magnetic fields including those in the ELF regions affect cell membrane functions, particularly the movement of Ca2+ across the membrane (3639). Since the Ca2+ ion is an integral part of various cellular signaling pathways involving protein kinases, ELF-magnetic fields have the potential to modulate the cellular response of a variety of DNA damaging agents whose mechanisms of action are linked to serine/threonine kinases, such as ionizing radiation (40). The possibility that activation of cellular ion channels may be connected to an induction of DNA repair pathway (41) is consistent with recent findings that potassium channel blockers such as cesium chloride significantly reduced radiation-induced mutagenesis in CHO cells (24).
The utilization of a sensitive in vitro mutagenic assay presents advantages over human epidemiological studies in the low-dose risk assessment. Because of the exquisite sensitivity of the AL cell system, the effects of low doses of radiation or chemicals can be studied, which would be quite impossible to detect in human epidemiological surveys or in most experimental animal systems. AL cells contain a full complement of hamster chromosomes, but only one copy of human chromosome 11. Except for a small segment near the distal end, most of this chromosome is not essential for the survival of AL cells, hence the entire chromosome can act as a target for mutagens and mutational damage in this chromosome is unlikely to be lost by cell death due to damage to neighboring essential genes (32,33). Therefore, a higher induction of mutants is expected, especially from mutagens that induce predominantly large multilocus deletions such as ionizing radiation and asbestos fibers (3335).
Our present study also addresses several critical issues that are frequently overlooked in EMF studies. Throughout this study, we have used a standardized EMF exposure system that has been approved by the US National Institute of Environmental Health Sciences, namely the MC-2XC concentric coil in vitro exposure system. This study also focuses on the effects of both short- and long-term EMF exposure and at the same time considered the co-mutagenic effects of EMF with low and high doses of known environmental carcinogens. Moreover, we use an index of EMF strength most relevant to residential and some occupational exposure levels.
Judging from the data for cell survival rates and CD59- mutant induction in cells treated with EMF for either a 24 h or 7 day period, we can conclude that short- or long-term exposure to a 100 µT 60 Hz alternating EMF is non-toxic and non-mutagenic by itself in a mammalian mutagenic assay system. These data are consistent with recent laboratory studies suggesting that 60 Hz EMF exposure has little or no effect on cancer development in F344/N rats or B6C3F1 mice (42,43). In two separate 2 year whole-body exposure studies on rats and mice, Boorman and colleagues reported no increases in incidence of the cancer types that have previously been identified in epidemiology studies as possible targets of EMF exposure: leukemia, breast cancer and brain cancer (42,43). Surprisingly, they even found reductions in different neoplastic transformations at various magnetic field strengths. While these reductions in incidence cannot be interpreted to be biologically significant, they are in agreement with our current findings and those of others suggesting a negative association between EMF exposure and cancer induction.
Our present findings are also consistent with other laboratory studies indicating an absence of an additive effect between EMF and other carcinogens. As described earlier, Mittler found no difference in mutagenic potential between X-irradiated Drosophilia with or without concurrent magnetic field treatment (26). In two recent studies, Anderson and colleagues found no evidence that 50 or 60 Hz magnetic fields promote breast cancer in the DMBA initiationpromotion mammary gland model in SpragueDawley rats (44,45).
In conclusion, this study shows that a 100 µT alternating 60 Hz EMF is non-cytotoxic and non-mutagenic by itself in mammalian cells. Furthermore, it does not increase the cytotoxicity or mutagenic potential of either physical or chemical carcinogens. These results provide supporting evidence to earlier studies which show that alternating EMF are not carcinogenic and do not have a co-mutagenic effect with physical carcinogens.
 |
Notes
|
---|
1 To whom correspondence should be addressedEmail: tkh1{at}columbia.edu 
 |
Acknowledgments
|
---|
This work was supported in part by NIH grants ES-08926 and ES-07890.
 |
References
|
---|
-
Boorman,G.A., Gauger,J.R., Johnson,T.R., Tomlinson,M.J., Findlay,J.C., Travlos,G.S. and McCormick,D.L. (1997) Eight-week toxicity study of 60 Hz magnetic fields in F344 rats and B6C3F1 mice. Fundam. Appl. Toxicol., 35, 5563.[ISI][Medline]
-
Wertheimer,N. and Leeper,E. (1979) Electrical wiring configurations and childhood cancer. Am. J. Epidemiol., 109, 273284.[Abstract]
-
Savitz,D.A. and Zuckerman,D.L. (1987) Childhood cancer in the Denver metropolitan area 19761983. Cancer, 59, 15391542.[ISI][Medline]
-
Ahlbom,A. (1988) A review of the epidemiological literature on magnetic fields and cancer. Scand. J. Work Environ. Health, 14, 337343.[ISI][Medline]
-
Shelikh,K. (1986) Exposure to electromagnetic fields and the risk of leukemia. Arch. Environ. Health., 41, 5663.[ISI][Medline]
-
Barnes,F., Wachtel,H., Savitz,D. and Fuller,J. (1989) Use of wiring configuration and wiring codes for estimating externally generated electric and magnetic fields. Bioelectromagnetics, 10, 1321.[ISI][Medline]
-
Fulton,J.P., Cobb,S., Preble,L., Leone,L. and Forman,E. (1980) Electrical wiring configurations and childhood leukemia in Rhode Island. Am. J. Epidemiol., 111, 292296.[Abstract]
-
Meyers,A., Clayden,A.D., Cartwright,R.A. and Cartwright,S.C. (1990) Childhood cancer and overhead powerlines: A case-control study. Br. J. Cancer, 62, 10081014.[ISI][Medline]
-
London,S.J., Thomas,D.C., Bowman,J.D., Sobel,E., Cheng,T.C. and Peters,J.M. (1991) Exposure to residential electric and magnetic fields and risk of childhood leukemia. Am. J. Epidemiol., 134, 923937.[Abstract]
-
Theriault,G., Goldberg,M., Miller,A.B., Armstrong,B., Guenel,P., Deadman,J., Imbernon,E., To,T., Chevailer,A., Cyr,D. and Wall,C. (1994) Cancer risks associated with occupational exposure to magnetic fields among electrical utility workers in Ontario and Quebec, Canada and France: 19701989. Am. J. Epidemiol., 139, 550572.[Abstract]
-
Savitz,D.A. and Loomis,D.P. (1995) Magnetic field exposure in relation to leukemia and brain mortality among electric utility workers. Am. J. Epidemiol., 141, 123134.[Abstract]
-
Demers,P.A., Thomas,D.B., Rosenblatt,K.A., Jimenez,L.M., McTiernan,A., Stalsberg,H., Stemhagen,A., Thompson,W.D., Curnen,M.G.M., Satariano,W., Austin,D.F., Isacson,P., Greenberg,R.S., Key,C., Kolonel,L.N. and West,D.W. (1991) Occupational exposure to electromagnetic fields and breast cancer in men. Am. J. Epidemiol., 134, 340347.[Abstract]
-
National Radiological Protection Board (1992) Electromagnetic Fields and the Risk of Cancer. NRPB, Chilton, UK.
-
Feychting,M., Florssen,U. and Floderus,B. (1997) Occupational and residential magnetic field exposure and leukemia and central nervous system tumors. Epidemiology, 8, 384389.[ISI][Medline]
-
Johansen,C. and Olsen,J.H. (1998) Risk of cancer among Danish utility workersA nationwide cohort study. Am. J. Epidemiol., 147, 548555.[Abstract]
-
Tynes,T. and Haldorsen,T. (1997) Electromagnetic fields and cancer in children residing near Norwegian high-voltage power lines. Am. J. Epidemiol., 145, 219226.[Abstract]
-
Hall,E.J. and Hei,T.K. (1990) Modulating factors in the expression of radiation induced oncogenic transformation. Environ. Health Perspect., 88, 149155.[ISI][Medline]
-
Hecht,S.S. and Hoffman,D. (1988) Tobacco specific nitrosoamines, an important group of carcinogens in tobacco and tobacco smoke. Carcinogenesis, 9, 875884.[Abstract]
-
Hei,T.K., Geard,C.R., Osmak,R.S. and Travisano,M. (1985) Correlation of in vitro genotoxicity and oncogenicity induced by radiation and asbestos fibers. Br. J. Cancer, 52, 591597.[ISI][Medline]
-
World Health Organization (1987) Magnetic Fields. WHO Environmental Health Criteria, 69, Geneva, Switzerland.
-
Rannug,A., Holmberg,B., Ekstrom,T., Mild,H.K., Gimenez-Conti,I. and Slaga,T. (1994) Intermittent 50 Hz magnetic field and skin tumor promotion in SENCAR mice. Carcinogenesis, 15, 153157.[Abstract]
-
Beniashvili,D.S., Bilanishvili,V. and Menabede,M.Z. (1996) Low frequency electromagnetic radiation enhances the induction of rat mammary tumors by MNU. Cancer Lett., 61, 7579.
-
Murphy,J.C., Kaden,D.A., Warren,J. and Sivak,A. (1993) Power frequency electric and magnetic fields: A review of genetic toxicology. Mutat. Res., 296, 221240.[ISI][Medline]
-
Saad,A.H., Zhou,L.Y., Lambe,E.K. and Hahn,G.M. (1994) Mutagenesis in mammalian cells can be modulated by radiation induced voltage dependent potassium channels. Mutat. Res., 324, 171176.[ISI][Medline]
-
Miyakoshi,J., Yamagishi,N. and Takepe,H. (1996) Increase in HGPRT gene mutation by exposure to high-density 50 Hz magnetic field. Mutat. Res., 349, 109114.[ISI][Medline]
-
Mittler,S. (1971) Failure of magnetism to influence production of X-ray induced sex-linked recessive lethals. Mutat. Res., 13, 287288.[ISI]
-
Feychting,M. and Ahlbom,A. (1993) Magnetic fields and cancer in children residing near Swedish highvoltage power lines. Am. J. Epidemiol., 138, 467481.[Abstract]
-
Kavet,R. (1995) Magnetic field exposure assessment. In Black,M. (ed.) Electromagnetic Fields: Biological Interactions and Mechanisms. American Chemical Society, Washington, DC, pp. 191223.
-
Kleczkowska,H.E. and Althaus,F.R. (1996) Response of human keratinocytes to extremely low concentrations of N-methyl-N'-nitro-N-nitrosoguanidine. Mutat. Res., 367, 151159.[ISI][Medline]
-
Waldren,C., Jones,C. and Puck,T.T. (1979) Measurement of mutagenesis in mammalian cells. Proc. Natl Acad. Sci. USA, 76, 13581362.[Abstract]
-
Puck,T.T., Wuchier,P., Jones,C. and Kao,F.T. (1971) Genetics of somatic mammalian cells: lethal antigens and genetic markers for study of human linkage. Proc. Natl Acad. Sci. USA, 68, 31023106.[Abstract]
-
Waldren,C., Correll,L., Sognier,M.A. and Puck,T.T. (1986) Measurement of low levels of X-ray mutagenesis in relation to human disease. Proc. Natl Acad. Sci. USA, 83, 48394843.[Abstract]
-
Hei,T.K., Piao,C.Q., He,Z.Y., Vannais,D. and Waldren,C.A. (1992) Chrysotile fiber is a strong mutagen in mammalian cells. Cancer Res., 52, 63056309.[Abstract]
-
Hei,T.K., Liu,S.X. and Waldren,C. (1998) Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species. Proc. Natl Acad. Sci. USA, 95, 81038107.[Abstract/Free Full Text]
-
Hei,T.K., Wu,L.J., Liu,S.X., Vannais,D., Waldren,C.A. and Randers-Pehrson,G. (1997) Mutagenic effects of a single and an exact number of alpha particles in mammalian cells. Proc. Natl Acad. Sci. USA, 94, 37653770.[Abstract/Free Full Text]
-
Bawin,S.M. and Adey,W.R. (1976) Sensitivity of calcium binding in cerebral tissue to weak environmental electric fields oscillating at low frequency. Proc. Natl Acad. Sci. USA, 73, 19992003.[Abstract]
-
Blackman,C.F., Benane,S.G., House,D.E. and Elliott,D.J. (1990) Importance of alignment between local DC magnetic field and an oscillating magnetic field in responses of brain tissue in vitro and in vivo. Bioelectromagnetics, 11, 159167.[ISI][Medline]
-
Luben,R.A. (1991) Effects of low-energy magnetic fields (pulsed and DC) on membrane signal transduction processes in biological systems. Health Phys., 61, 1528.[ISI][Medline]
-
Walleczek,J. (1992) Electromagnetic field effects on cells of the immune system: the role of calcium signaling. FASEB J., 6, 31773185.[Abstract/Free Full Text]
-
Byus,C.V., Lundak,R.L., Fletcher,R.M. and Adey,W.R. (1984) Alterations in protein kinase activity following exposure of cultured human lymphocytes to modulated microwave fields. Bioelectromagnetics, 5, 341351.[ISI][Medline]
-
Adey,W.R. (1993) Biological effects of electromagnetic fields. J. Cell Biochem., 51, 410416.[ISI][Medline]
-
Boorman,G.A., McCormick,D.L., Findlay,J.C., Hailey,J.R., Gauger,J.R., Johnson,T.R., Kovatch,R.M., Sills,R.C. and Haseman,J.K. (1999) Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in F344/N rats. Toxicol. Pathol., 27, 267278.[ISI][Medline]
-
McCormick,D.L., Boorman,G.A., Findlay,J.C., Hailey,J.R., Johnson,T.R., Gauger,J.R., Pletcher,J.M., Sills,R.C. and Haseman,J.K. (1999) Chronic toxicity/oncogenicity evaluation of 60 Hz (power frequency) magnetic fields in B6C3F1 mice. Toxicol. Pathol., 27, 279285.[ISI][Medline]
-
Boorman,G.A., Anderson,L.E., Morris,J.E., Sasser,L.B., Mann,P.C., Grumbein,S.L., Hailey,J.R., McNally,A., Sills,R.C. and Haseman,J.K. (1999) Effect of 26 week magnetic field exposures in a DMBA initiationpromotion mammary gland model in SpragueDawley rats. Carcinogenesis, 20, 899904.[Abstract/Free Full Text]
-
Anderson,L.E., Boorman,G.A., Morris,J.E., Sasser,L.B., Mann,P.C., Grumbein,S.L., Hailey,J.R., McNally,A., Sills,R.C. and Haseman,J.K. (1999) Effect of 13 week magnetic field exposures on DMBA-initiated mammary gland carcinomas in female SpragueDawley rats. Carcinogenesis, 20, 16151620.[Abstract/Free Full Text]
Received November 24, 1999;
revised February 24, 2000;
accepted February 29, 2000.