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PubMed1981

General properties of the interaction between animals and ELF electric fields.

An analysis is given of the interaction between extremely low-frequency (ELF) electric fields and animals of arbitrary body shape. This analysis is based on three approximations which are valid in the ELF range: In living tissues, capacitive (displacement) currents are negligible compared to conduction currents; effects resulting from the finite velocity of propagation of electromagnetic fields are negligible; skin effect in living tissues is negligible. Major conclusions of the analysis are: (a) The electric field outside the body, the induced charge on the surface of the body, and the total current crossing any section through the body (eg, through the neck or limbs) are completely determined by the characteristics of the applied ELF electric field, the shape of the body, its location relative to ground and other conductors, and any conduction currents from the body to ground or other conductors. (b) All of the quantities in (a) can be measured using conducting animal models. (c) The magnitudes of the electric field outside the body and the induced charge density on the surface of the body are independent of frequency, in the ELF range, when the body is either insulated from or shorted to ground (and any other conductors in the system). (d) The only quantities affected by the electrical properties of the tissues comprising the body are the current density and electric field inside the body. (e) The electric field outside and inside a body will be unchanged by a scaled change in its size.

Air↗
PubMed1988

Chronic exposure to ELF fields may induce depression.

Exposure to extremely-low-frequency (ELF) electric or magnetic fields has been postulated as a potentially contributing factor in depression. Epidemiologic studies have yielded positive correlations between magnetic- and/or electric-field strengths in local environments and the incidence of depression-related suicide. Chronic exposure to ELF electric or magnetic fields can disrupt normal circadian rhythms in rat pineal serotonin-N-acetyltransferase activity as well as in serotonin and melatonin concentrations. Such disruptions in the circadian rhythmicity of pineal melatonin secretion have been associated with certain depressive disorders in human beings. In the rat, ELF fields may interfere with tonic aspects of neuronal input to the pineal gland, giving rise to what may be termed "functional pinealectomy." If long-term exposure to ELF fields causes pineal dysfunction in human beings as it does in the rat, such dysfunction may contribute to the onset of depression or may exacerbate existing depressive disorders.

Animals↗
PubMed1995

Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map.

Topographic maps with a defined spatial ordering of neuronal connections are a key feature of brain organization. Such maps are believed to develop in response to complementary position-specific labels in presynaptic and postsynaptic fields. However, the complementary labeling molecules are not known. In the well-studied visual map of retinal axons projecting to the tectum, the labels are hypothesized to be in gradients, without needing large numbers of cell-specific molecules. We recently cloned ELF-1 as a ligand for Eph family receptors. Here, RNA hybridization shows matching expression gradients for ELF-1 in the tectum and its receptor Mek4 in the retina. Binding activity detected with alkaline phosphatase fusions of ELF-1 and Mek4 also reveals gradients and provides direct evidence for molecular complementarity of gradients in reciprocal fields. ELF-1 and Mek4 may therefore play roles in retinotectal development and have properties predicted of topographic mapping labels.

Amino Acid Sequence↗
PubMed2003

The level of MEF but not ELF-1 correlates with FAB subtype of acute myeloid leukemia and is low in good prognosis cases.

ETS proteins (such as PU.1, Fli-1 and ETS-1) have been shown to play important roles in normal and abnormal hematopoiesis. We examined the expression of the ELF subfamily of ETS genes (ELF-1, MEF and NERF) in acute myeloid leukemia (AML) cells using Northern blot analysis. ELF-1 and MEF were expressed in all samples, whereas NERF was not. The relative expression (RE) of MEF, but not ELF-1, was significantly lower (P<0.0001) in AML with t(8;21) and t(15;17) compared with AML with normal karyotype. The pattern of MEF expression was not uniform among cells with CD34(+)/CD33(+). It is suggested that the low RE of MEF might be part of a gene expression profile characterizing AML with a good prognosis.

Acute Disease↗
PubMed2003

The effect of extremely low frequency electromagnetic fields (ELF-EMF) on the frequency of micronuclei and sister chromatid exchange in human lymphocytes induced by benzo(a)pyrene.

The interaction of extremely low frequency electromagnetic fields (ELF-EMF) on the frequency of micronuclei (MN) and sister chromatid exchange (SCE) induced by benzo(a)pyrene (BP) in human lymphocytes was examined. A 60 Hz ELF-EMF of 0.8 mT field strength was applied either alone or with the tumor initiator, BP for 24 h. The frequencies of MN and SCE induced by BP increased in a dose-dependent manner. The co-exposure of cells to BP and 0.8 mT ELF-EMF for 24 h, followed by BP exposure for 48 h led to significant increases in the frequencies of MN and SCE compared to BP treatment for 72 h alone (P<0.05), but no significant difference was observed between field exposed and sham exposed control cells. The obtained results suggest that low density ELF-EMF could act as an enhancer of the initiation process of BP rather than as an initiator of mutagenic effects in human lymphocytes.

Benzo(a)pyrene↗
PubMed1992

A novel Ets-related transcription factor, Elf-1, binds to human immunodeficiency virus type 2 regulatory elements that are required for inducible trans activation in T cells.

Human immunodeficiency virus type 1 (HIV-1) and HIV-2 are structurally related retroviruses which both cause AIDS in humans. Although both viruses establish latency in quiescent human-peripheral-blood T cells, the asymptomatic phase of HIV-2 infection may be more prolonged than that of HIV-1. The latent phases of both HIV-1 and HIV-2 infection have been shown to be disrupted by T-cell activation, a process that requires host cell transcription factors. In the case of HIV-1, the transcription factor NF-kappa B is sufficient for inducible transcriptional activation. In contrast, factors in addition to NF-kappa B are required to activate HIV-2 transcription in infected T cells. In this report, we demonstrate that a novel Ets-related transcription factor, Elf-1, binds specifically to two purine-rich motifs in the HIV-2 enhancer. Mutagenesis experiments demonstrated that these Elf-1 binding sites are required for induction of HIV-2 transcription following T-cell-receptor-mediated T-cell activation. Moreover, Elf-1 is the only factor present in activated T-cell nuclear extracts that binds to these sites in electrophoretic mobility shift assays. Thus, Elf-1 is a novel transcription factor that appears to be required for the T-cell-receptor-mediated trans activation of HIV-2 gene expression. These results may explain differences in the clinical spectra of diseases caused by HIV-1 and HIV-2 and may also have implications for the design of therapeutic approaches to HIV-2 infection.

Adult↗
PubMed1992

cis-acting sequences required for inducible interleukin-2 enhancer function bind a novel Ets-related protein, Elf-1.

The recent definition of a consensus DNA binding sequence for the Ets family of transcription factors has allowed the identification of potential Ets binding sites in the promoters and enhancers of many inducible T-cell genes. In the studies described in this report, we have identified two potential Ets binding sites, EBS1 and EBS2, which are conserved in both the human and murine interleukin-2 enhancers. Within the human enhancer, these two sites are located within the previously defined DNase I footprints, NFAT-1 and NFIL-2B, respectively. Electrophoretic mobility shift and methylation interference analyses demonstrated that EBS1 and EBS2 are essential for the formation of the NFAT-1 and NFIL-2B nuclear protein complexes. Furthermore, in vitro mutagenesis experiments demonstrated that inducible interleukin-2 enhancer function requires the presence of either EBS1 or EBS2. Two well-characterized Ets family members, Ets-1 and Ets-2, are reciprocally expressed during T-cell activation. Surprisingly, however, neither of these proteins bound in vitro to EBS1 or EBS2. We therefore screened a T-cell cDNA library under low-stringency conditions with a probe from the DNA binding domain of Ets-1 and isolated a novel Ets family member, Elf-1. Elf-1 contains a DNA binding domain that is nearly identical to that of E74, the ecdysone-inducible Drosophila transcription factor required for metamorphosis (hence the name Elf-1, for E74-like factor 1). Elf-1 bound specifically to both EBS1 and EBS2 in electrophoretic mobility shift assays. It also bound to the purine-rich CD3R element from the human immunodeficiency virus type 2 long terminal repeat, which is required for inducible virus expression in response to signalling through the T-cell receptor. Taken together, these results demonstrate that multiple Ets family members with apparently distinct DNA binding specificities regulate differential gene expression in resting and activated T cells.

Adult↗
PubMed1996

Characterization of NERF, a novel transcription factor related to the Ets factor ELF-1.

We have cloned the gene for a novel Ets-related transcription factor, new Ets-related factor (NERF), from human spleen, fetal liver, and brain. Comparison of the deduced amino acid sequence of NERF with those of other members of the Ets family reveals that the level of homology to ELF-1, which is involved in the regulation of several T- and B-cell-specific genes, is highest. Homologies are clustered in the putative DNA binding domain in the middle of the protein, a basic domain just upstream of this domain, and several shorter stretches of homology towards the amino terminus. The presence of two predominant NERF transcripts in various fetal and adult human tissues is due to at least three alternative splice products, NERF-1a, NERF-1b, and NERF-2, which differ in their amino termini and their expression in different tissues. Only NERF-2 and ELF-1, and not NERF-1a and NERF-1b, function as transcriptional activators of the lyn and blk gene promoters, although all isoforms of NERF bind with affinities similar to those of ELF-1 to a variety of Ets binding sites in, among others, the blk, lck, lyn, mb-1, and immunoglobulin H genes and are expressed at similar levels. Since NERF and ELF-1 are coexpressed in B and T cells, both might be involved in the regulation of the same genes.

Adult↗
PubMed2001

PU.1 exhibits partial functional redundancy with Spi-B, but not with Ets-1 or Elf-1.

Previously it was shown that the Ets proteins, PU.1 and Spi-B, exhibit functional redundancy in B lymphocytes. To investigate the possibility that PU.1 or Spi-B or both share overlapping roles with Ets-1 or Elf-1, PU.1(+/-)Ets-1(-/-), PU.1(+/-)Elf-1(-/-), and Spi-B(-/-)Ets-1(-/-) animals were generated. No blood cell defects were observed in these animals except those previously reported for Ets-1(-/-) mice. Therefore, no genetic overlap was detected between PU.1 or Spi-B with Ets-1 or Elf-1. In contrast, the results confirmed functional redundancy for PU.1 and Spi-B in that PU.1(+/-)Spi-B(-/-) bone marrow progenitors yielded smaller colonies in methylcellulose cultures than did wild-type, PU.1(+/-) or Spi-B(-/-) progenitors. In addition, PU.1(+/-)Spi-B(+/+), PU.1(+/-)Spi-B(+/-), and PU.1(+/-) Spi-B(-/-) mice displayed extramedullary splenic hematopoiesis. In summary, PU.1 and Spi-B regulate common target genes required for proliferation of hematopoietic progenitors or their committed descendants, whereas Ets-1 or Elf-1 do not appear to regulate shared target genes with PU.1 or Spi-B.

Animals↗
PubMed1987

Cancer incidence among welders: possible effects of exposure to extremely low frequency electromagnetic radiation (ELF) and to welding fumes.

Epidemiological studies of cancer incidence among welders disclose a pooled total of 146 cases of leukemia observed versus 159.46 expected, a risk ratio of 0.92, and 40 cases of acute leukemia observed versus 43.39 expected, a risk ratio of 0.92. For respiratory tract cancer, the pooled total is 1789 cases observed versus 1290.7 expected, a risk ratio of 1.39. Most electric welders are exposed to extremely low frequency electromagnetic radiation (ELF) (magnetic flux densities of up to 100,000 microT), a suspected leukemogen, and to concentrated metallic aerosols (up to 200 mg/m3), which can contain the putative respiratory tract carcinogens Cr(VI) and Ni. The two exposures are usually coincident, since welding with an electric current produces welding fumes. The observation of an excess risk for respiratory tract cancer strongly suggests significant exposure both to fumes and to ELF. The absence of increased risk for all leukemia or for acute leukemia among ELF-exposed welders does not support the hypothesis that the observed excess risk for leukemia or acute leukemia among workers in the electrical trades is due to their ELF exposure, which on the average is lower than that of welders.

Air Pollutants, Occupational↗
PubMed1996

A 100 mT-class ELF magnetic field exposure system for cultured cells.

We developed a system for exposure of cultured cells to extremely low frequency (ELF) magnetic fields much stronger than those used in previous in vitro studies. The system consists of an electromagnet, a commercial incubator with a custom-designed door and a custom-designed shelf, and other components, and exposes cells in the incubator to ELF magnetic field. We confirmed that it has good performance characteristics in terms of field intensity, field uniformity, waveform, field stability, temperature uniformity, and temperature stability. Its features include: (1) strong ELF magnetic fields (at most, 170 mTRMS), (2) long-term exposure (at least, 5.5 h), and (3) variable frequencies (10-100 Hz). This exposure system is expected to contribute significantly to research on possible hazards of ELF magnetic fields.

Cells, Cultured↗
PubMed1997

Need for a European approach to the effects of extremely low-frequency electromagnetic fields on cancer. ELF-EMF European Feasibility Study Group.

BACKGROUND: A European feasibility study on environmental exposure to extremely low-frequency electromagnetic fields (ELF-EMF) and cancer was conducted. The study was motivated by public health concern about possible adverse health effects associated with ELF-EMF exposure. METHODS: A review of completed research in Europe was conducted. Information on the methods and accessibility of new epidemiologic studies were requested and reviewed. RESULTS: Eight studies on environmental ELF-EMF exposure have been completed in Europe while 15 large studies are in progress. Although there is no known mechanism by which electric or magnetic fields of this frequency could play a role in the development of cancer or other adverse health effects, the results of the studies conducted so far provide some support for the hypothesis that they are associated with the incidence of childhood leukemia. CONCLUSIONS AND RECOMMENDATIONS: The best use of available data will be made through a pooled re-analysis of data, particularly those on childhood tumors. It is recommended to apply multiple methods for exposure assessment in view of the heterogeneity in the methods used in different studies. New multicenter case-referent studies should not be initiated until the results of the large on-going studies have been reported. Prospective cohort studies will have to be very large to identify moderate excess risks resulting from environmental exposure to ELF-EMF, and their feasibility should be discussed after the results of the on-going case-referent studies have been reported. A European collaborative approach will lead to greater statistical power and will assess the exposure-effect association under differing exposure patterns and distributions of potential confounding factors.

Adult↗
PubMed1999

Elf-1 and PU.1 induce expression of gp91(phox) via a promoter element mutated in a subset of chronic granulomatous disease patients.

The cytochrome b heavy chain (gp91(phox)) is the redox center of the NADPH-oxidase and is highly expressed in mature myeloid cells. Point mutations at -57, -55, -53, and -52 bp of the gp91(phox) promoter have been detected in patients with chronic granulomatous disease (CGD; Newburger et al, J Clin Invest 94:1205, 1994; and Suzuki et al, Proc Natl Acad Sci USA 95:6085, 1998). We report that Elf-1 and PU. 1, ets family members highly expressed in myeloid cells, bind to this promoter element. Either factor trans-activates the -102 to +12 bp gp91(phox) promoter when overexpressed in nonhematopoietic HeLa cells or the PLB985 myeloid cell line. However, no synergy of gp91(phox) promoter activation occurs when both Elf-1 and PU.1 are overexpressed. Introduction of the -57 bp or -55 bp CGD mutations into the gp91(phox) promoter significantly reduces the binding affinity of Elf-1 and PU.1 and also reduces the ability of these factors to trans-activate the promoter. These results indicate that Elf-1 and PU.1 contribute to directing the lineage-restricted expression of the gp91(phox) gene in phagocytes and that failure of these factors to effectively interact with this promoter results in CGD.

Base Sequence↗
PubMed2000

[Preliminary clinical comparison of HLF and ELF regimen in the treatment of advanced gastric carcinoma in middle-aged and elderly patients].

OBJECTIVE: To observe the therapeutic effects and toxicity of HLF (hydroxycamptothecin HCPT/leucovorin LV/fluorouracil 5-Fu) regimen and ELF (etoposide VP-16/LV/5-Fu) regimen in middle-aged and elderly patients with advanced gastric carcinoma. METHODS: A group of twenty-five cases were treated with HLF regimen, and the other group of 23 cases were treated with ELF regimen. RESULTS: Of the 25 cases treated with HLF regimen, there was no complete remission (CR), but there were 12 partial response (PR), 11 no response (NC), and 2 had progressive disease (PD). The response rate (RR) was 48.0%. Of the 23 patients treated with ELF regimen, there was no CR, there were 9 PR, 11 NC, and 3 PD. The RR was 39.1% (P > 0.05). The main toxicity was myelosuppression and stomatocace. Grade III-IV stomatocace in HLF regimen group (68.0%) was more commonly seen than that in ELF regimen group (39.1%, P < 0.05). There was no cardiac or renal toxicity observed. CONCLUSION: HLF regimen is promising for treatment of advanced gastric carcinoma in middle-aged and elderly patients with the merits of low toxicity affecting heart, kidney and bladder except stomatocace, which is worthy of further clinical trial.

Aged↗
PubMed1994

ELF magnetic field exposures in an office environment.

Potential exposures to extremely low frequency (ELF) magnetic fields were investigated in response to worker concerns about an apparent increased spontaneous abortion risk in a payroll office environment. Concern in this office centered on the use of video display terminals (VDTs), which have been investigated as a potential cause of adverse reproductive outcomes among women. In this investigation, magnetic field sources were evaluated using a hand-held survey meter. Emdex datalogging dosimeters were also used to determine full shift personal exposures for 15 women working in the payroll area. On average, the exposures of workers to ELF magnetic fields in the payroll office area ranged from 1.0 to 6.5 mG with a mean of 3.2 +/- 1.5 mG. The results of this study indicate that many sources of ELF magnetic fields, including printers, photocopiers, and the electrical distribution system, can contribute to a worker's exposure in an office environment.

Computer Terminals↗
PubMed1993

Biological, physical, and electrical parameters for in vitro studies with ELF magnetic and electric fields: a primer.

This paper presents material which is intended to assist researchers in identifying and controlling a range of biological, electrical, and other physical parameters that can affect the outcome of in vitro studies with extremely low frequency (ELF) magnetic and electric fields. Brief descriptions of power line magnetic and electric fields are provided and methods for the generation of 60 Hz as well as other ELF fields in the laboratory are surveyed. Methods for calculating and measuring exposure parameters in culture medium are also described. Relating in vitro and internal in vivo exposure conditions across different animal species is discussed to aid researchers in selecting levels of field exposure. The text is purposely elementary, and sometimes brief, with references provided to aid the interested reader in obtaining a fuller understanding of the many topics. Because the range of experimental parameters that can influence the outcome of in vitro studies with ELF fields is so broad, a multidisciplinary approach is normally required to carry out the research.

Animals↗
PubMed2001

Do cocarcinogenic effects of ELF electromagnetic fields require repeated long-term interaction with carcinogens? Characteristics of positive studies using the DMBA breast cancer model in rats.

The carcinogenic or cocarcinogenic potential of extremely low frequency (ELF; 50 or 60 Hz) magnetic fields (MFs) has been evaluated worldwide in diverse animal model systems. Though most results have been negative, weakly positive or equivocal results have been reported in several cancer models, including the rat DMBA (7,12-dimethylbenz[a]anthracene) model of mammary cancer. Based on the experimental conditions used in studies in which cocarcinogenic effects of ELF MF were found, it was recently proposed that MF exposure may potentiate the effects of known carcinogens only when the animals are exposed to both MF and carcinogen during an extended period of tumor development, i.e., when the carcinogen is given repeatedly during MF exposure. This review summarizes a series of experiments from our group, showing cocarcinogenic MF effects in the DMBA breast cancer model in rats, to test whether the above proposal is confirmed by existing data. Flux densities of 50 or 100 microT significantly increased the growth of mammary tumors, independent of whether DMBA was given in a single administration or repeatedly over a prolonged period. Thus, these data do not substantiate the hypothesis requiring repeated doses of DMBA during MF exposure. Instead, several other aspects of study design and experimental factors are identified that seem to be critical for the detection of cocarcinogenic effects of MF exposure in the rat DMBA mammary cancer model. These include the rat subline used, the dose of DMBA, the duration of MF exposure, the flux density, the background (sham control) tumor incidence, and the location of mammary tumors in the mammary gland complex. These and other experimental aspects may explain why some laboratories did not detect cocarcinogenic MF effects in the DMBA model. We hope that direct comparison of MF bioeffects in different rat sublines and further evaluation of other experimental differences between studies on MF exposure in the DMBA model will eventually determine which genetic and environmental factors are critical for potential carcinogenic or cocarcinogenic effects of ELF MF exposure.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

IgM receptor-mediated transactivation of the IgH 3' enhancer couples a novel Elf-1-AP-1 protein complex to the developmental control of enhancer function.

The function of the temporally regulated B lymphocyte-specific immunoglobulin heavy chain (IgH) 3' enhancer has been linked to the IgH class switch machinery, but the physiological mechanism(s) of activation has not been discerned. Following crosslinking of the IgM receptor, we demonstrate that the enhancer is transactivated in the B lymphoma cell line BAL-17. In both induced primary B lymphocytes and BAL-17 cells, the enhancer activation is concomitant with the recruitment of a novel DNA binding complex, nuclear factor of activated B cells (NFAB). NFAB contains the tissue-restricted Ets protein Elf-1 and the AP-1 factors Jun-B and c-Fos, which bind to a novel 3' enhancer ETS-AP-1 motif. IgM receptor-mediated activation or stimulation by phorbol-ester in BAL-17 cells demonstrates that the ETS-AP-1 motif, when linked to a heterologous gene, can confer a ligand/receptor-dependent response. In NIH 3T3 cells, Elf-1 expression is required for efficient ETS-AP-1 promoter activity in response to stimulation by 12-O-tetradecanylphorbol 13-acetate. Our results suggest a biological role for Elf-1 in the regulation of IgH gene expression, attribute a functional role for receptor-induced AP-1 proteins in B lymphocytes and provide evidence for a direct link between IgM receptor-mediated signalling and 3' enhancer activation.

Animals↗