Reba Goodman

Insights into electromagnetic interaction mechanisms.

Low frequency (< 300 Hz) electromagnetic (EM) fields induce biological changes that include effects ranging from increased enzyme reaction rates to increased transcript levels for specific genes. The induction of stress gene HSP70 expression by exposure to EM fields provides insight into how EM fields interact with cells and tissues. Insights into the mechanism(s) are also provided by examination of the interaction of EM fields with moving charges and their influence on enzyme reaction rates in cell‐free systems. Biological studies with in vitro model systems have focused, in general, on the nature of the signal transduction pathways involved in response to EM fields. It is likely, however, that EM fields also interact directly with electrons in DNA to stimulate biosynthesis. Identification of an EM field‐sensitive DNA sequence in the heat shock 70 (HSP70) promoter, points to the application of EM fields in two biomedical applications: cytoprotection and gene therapy. EM field induction of the stress protein hsp70 may also provide a useful biomarker for establishing a science‐based safety standard for the design of cell phones and their transmission towers.

Increased levels of hsp70 transcripts induced when cells are exposed to low frequency electromagnetic fields

Abstract Previous experiments have shown that the steady state levels of some RNA transcripts are increased when cells are exposed to extremely low frequency electric or magnetic fields. Experiments have exposed a variety of cell types, including dipteran salivary gland cells, yeast and human HL-60 cells. The range of responsive transcripts includes oncogenes such as c-myc, as well as transcripts associated with growth and development. One hypothesized mechanism of how cells respond to electromagnetic (EM) fields assumes that the response represents or mimics a generalized physiological stress response. RNA from exposed HL-60 cells, previously shown to have increased transcript levels for c-myc, was analyzed for hsp70 transcripts levels. The hsp70 transcripts were found to be elevated in all cases, even though the cells were exposed to various fields at normal growth temperatures. The conditions of maximum induction for hsp70 were coordinate with those of c-myc. In yeast cells, the SSA1 gene (homologous to hsp70) was found to be elevated in cells exposed to EM fields at 0.8−80 μT. In the case of yeast, conditions for maximum induction of SSA1 were coordinate with those for URA3, the gene for uracil metabolism. Thus the model of cell interaction with electric and/or magnetic fields appears to be related to the stress response model for heat shock.

Magnetic field stress induces expression of hsp70

Magnetic fields with frequencies lower than 300 Hz and field strengths less than 1 Gauss (1000 mG) induce a variety of effects in cells and tissues (for reviews see Blank 1995; Goodman et al 1995; Hong 1995). Among these effects are altered transcription and translation, including hsp70 (Lin et al 1997, 1998) and the immediate early response genes myc, jun andfos (Philips et al 1992; Lin et al 1996; Jin et al 1997); increased enzyme activities of ornithine decarboxylase, Na, K-ATPase and cytochrome oxidase (Byus et al 1988; Blank 1995; Blank and Soo 1998); changes in melatonin release (Reiter 1995) and alterations in receptor binding (Luben 1995). The increased expression of stress genes in the presence of magnetic fields suggests that cells respond to magnetic fields as an environmental stress.

Do electromagnetic fields interact directly with DNA

The mechanisms whereby electromagnetic (EM) fields stimulate changes in biosynthesis in cells are not known. It has has generally been assumed that EM fields first interact with cell membranes, but this pathway may not be only one. Interactions with membranes are well documented, but recent studies of EM signal transduction in the membrane Na,K-ATPase are best explained by direct interaction of electric and magnetic fields with mobile charges within the enzyme. Interaction with moving charges may be a mechanism that is operative in other biopolymers. Recent studies on DNA have shown that large electron flows are possible within the stacked base pairs of the double helix. Therefore, gene activation by magnetic fields could be due to direct interaction with moving electrons within DNA. Electric fields as well as magnetic fields stimulate transcription, and both fields could interact with DNA directly. The mechanism of EM field-stimulated transcription may be related to the process in striated muscles, where endogenous electrical activity induces the synthesis of new proteins.

Transcription and translation in cells exposed to extremely low frequency electromagnetic fields

Abstract When dipteran salivary gland cells or human cells are exposed to low frequency electromagnetic fields, a pronounced increase in transcription can be measured. Changes in the protein synthetic pattern also occur. We have observed four major findings relative to transcriptional changes. These are: (1) the increase in mRNA levels is most likely due to an increased rate of transcription (rather than, for example, an increase in RNA stability); (2) frequency-, field strength and time-dependent “windows” are observed relative to quantitative changes in specific transcripts; (3) genes not normally expressed are unaffected by exposure to extremely low frequency electromagnetic fields and (4) changes in the overall protein synthetic patterns occur.

Effects of mobile phone radiation on reproduction and development in Drosophila melanogaster

In this report we examined the effects of a discontinuous radio frequency (RF) signal produced by a GSM multiband mobile phone (900/1,900 MHz; SAR ∼ 1.4 W/kg) on Drosophila melanogaster, during the 10‐day developmental period from egg laying through pupation. As found earlier with low frequency exposures, the non‐thermal radiation from the GSM mobile phone increased numbers of offspring, elevated hsp70 levels, increased serum response element (SRE) DNA‐binding and induced the phosphorylation of the nuclear transcription factor, ELK‐1. The rapid induction of hsp70 within minutes, by a non‐thermal stress, together with identified components of signal transduction pathways, provide sensitive and reliable biomarkers that could serve as the basis for realistic mobile phone safety guidelines. J. Cell. Biochem. 89: 48–55, 2003.

Regulating genes with electromagnetic response elements

A 900 base pair segment of the c‐myc promoter, containing eight nCTCTn sequences, is required for the induction of c‐myc expression by electromagnetic (EM) fields. Similarly, a 70 bp region of the HSP70 promoter, containing three nCTCTn sequences, is required for the induction of HSP70 expression by EM fields. Removal of the 900 base pair segment of the c‐myc promoter eliminates the ability of EM fields to induce c‐myc expression. Similarly, removal of the 70 bp region of the HSP70 promoter, with its three nCTCTn sequences, eliminates the response to EM fields. The nCTCTn sequences apparently act as electromagnetic field response elements (EMRE). To test if introducing EMREs imparts the ability to respond to applied EM fields, the 900 bp segment of the c‐myc promoter (containing eight EMREs) was placed upstream of CAT or luciferase reporter constructs that were otherwise unresponsive to EM fields. EMREs‐reporter constructs were transfected into HeLa cells and exposed to 8 μT 60 Hz fields. Protein extracts from EM field‐exposed transfectants had significant increases in activity of both CAT and luciferase, compared with identical transfectants that were sham‐exposed. Transfectants with CAT or luciferase constructs lacking EMREs remained unresponsive to EM fields, i.e., there was no increase in either CAT or luciferase activity. These data support the idea that EMREs can be used as switches to regulate exogenously introduced genes in gene therapy. J. Cell. Biochem. 81:143–148, 2001.

Electromagnetic field exposure induces rapid, transitory heat shock factor activation in human cells

Stimulation of human promyelocytic HL60 cells by a 60Hz magnetic field at normal growth temperatures results in heat shock factor 1 activation and heat shock element binding, a sequence of events that mediates the stress‐induced transcription of the stress gene HSP70 and increased synthesis of the stress response protein hsp70kD. Thus, the events mediating the electromagnetic field–stimulated stress response appear to be similar to those reported for other physiological stresses (e.g., hyperthermia, heavy metals, oxidative stress) and could well be the general mechanism of interaction of electromagnetic fields with cells. J. Cell. Biochem. 66:482–488, 1997.

Calcium is necessary in the cell response to EM fields

Previous research showed that exposure of human HL‐60 cells to extremely low frequency electromagnetic fields increases the steady‐state levels of some mRNAs. Modifications in calcium flux have been suggested as a means of amplifying electromagnetic signals, and induced changes in calcium influx could hypothetically lead to gene activation. The present experiments tested the role of calcium in the response of cells to electromagnetic fields. Steady state transcript levels for c‐fos and c‐myc were determined under conditions of low extracellular calcium. The present study confirms that calcium plays a role in the response of cells to electromagnetic fields.

A magnetic field‐responsive domain in the human HSP70 promoter

HSP70 gene expression is induced by a wide range of environmental stimuli, including 60‐Hz electromagnetic fields. In an earlier report we showed that the induction of HSP70 gene expression by magnetic fields is effected at the level of transcription and is mediated through c‐myc protein binding at two nCTCTn sequences at −230 and −160. in the human HSP70 promoter. We report on the identification of a third c‐myc binding site (between −158 and −162) that is an important regulator of magnetic field‐induced HSP70 expression. We also show that the heat shock element (HSE), lying between −180 and −203, is required for induction of HSP70 gene expression by magnetic fields. The HSE centered at −100 alone is insufficient. J. Cell. Biochem. 77:170–176, 1999.