REFLEX-Study – Final Report

Risk Evaluation of Potential Environmental Hazards From Low Frequency Electromagnetic Field Exposure Using Sensitive in vitro Methods

A project funded by the European Union
under the programme
Quality of Life and Management of Living Resources
Key Action 4 “Environment and Health”
Contract: QLK4-CT-1999-01574
Start date: 01 February 2000
End date: 31 May 2004
Acronym: REFLEX


Based on the state of knowledge acquired during the last 50 years of research on possible biological effects of electromagnetic fields (EMF), the majority of the scientific community is convinced that exposure to EMF below the existing security limits does not cause a risk to the health of the general public. However, this position is questioned by others, who are of the opinion, that the available research data are contradictory or inconsistent and therefore, unreliable. As a consequence, it is necessary that the methodology applied in EMF research to be considerably improved and complemented by the most recent molecular biological techniques. In the REFLEX project, biological effects of extremely low frequency
electromagnetic fields (ELF-EMF) and radio frequency electromagnetic fields (RF-EMF) are studied using sophisticated and diverse research methodologies separately since it is assumed that the generation of effects, if verifiable at all, may be based on different mechanisms.

Many laboratory investigations have been performed to test the hypothesis that ELF-EMF exposure may constitute a risk to the health of people. This hypothesis is almost entirely based on epidemiological studies, some of which indicate that ELF-EMF may contribute to the development of leukaemia in children, and other cancers in adults chronically exposed in residential environments or occupational settings (NRPB 2001; California EMF Program 2002; IARC Monographs 2002). The existing uncertainty is a source of increasing concern for the public, the health authorities and also the industry. In vitro studies have shown that ELF-EMF induces significant biological alterations in a variety of cells and tissues. These changes concern the up-regulation of several early response genes, including c-myc (Jin et al. 2000), c-fos (Rao and Henderson 1996) and hsp70 mRNA (Goodman and Blank 1998), thus increasing the production of stress inducible heat shock proteins (Goodman and Henderson 1988; Tokalov and Gutzeit 2003). In spite of this, it is still an unsolved issue whether or not exposure to ELFEMF may promote pathological processes such as carcinogenesis and if so, whether or not the field effects are exerted through mechanisms influencing the genome of cells, cell proliferation, differentiation or programmed cell death (apoptosis). Results from several studies have indicated that ELF-EMF does not exert any direct genotoxic effect, but may promote carcinogenesis indirectly by interfering with the signal transduction pathways of cells (Blackman et al. 1985; Liburdy et al.1993). Of course, the present uncertainty could considerably be diminished by increasing our knowledge on the parameters of the
electromagnetic field which are critical for the generation of biological effects and of the biological systems which are crucial for the occurrence of pathological cellular events.

As with ELF-EMF, several epidemiological and animal studies also cast suspicion on RF signals to promote cancer and other diseases in chronically exposed individuals (Stewart Report 2000; Hardell et al. 2003). Because of its overwhelming presence in our society, the potential influence of RF-EMF exposure on the development of adverse health effects has become a major topic of interest for all concerned, including the government, the general public, and the industry. Putatively non-thermal, immediate and reversible responses have been described in the literature for several years (Roschke and Mann 1997; Wagner et al.1998; Borbely et al.1999; Preece et al. 1999; Koivisto et al. 2000; Huber et al. 2000; Krause et al. 2000). However, these effects, because of their unspecific nature have been regarded as indications of potential biological responses to electrical excitation, rather than harmful effects able to produce permanent damage to health. To date, several in vitro studies have been carried out to investigate the disease causing potential of RF radiation. While most of these studies using different cell systems, exposure set-ups and molecular-biological and toxicological methodologies did not show any biological effect, increasing numbers of studies have come up with contradicting results (Moulder et al. 1999; Vescovic et al. 2002).

As stated above, although investigations of possible biological effects of EMF have been conducted for decades, reliable answers are still missing. Extensive epidemiological and animal studies commonly expected to provide the answer as to whether or not EMF might be hazardous are in progress. However, this approach alone might not be able to provide certain evidence whether EMF can or cannot contribute to the pathogenesis of diseases such as cancer or neurodegenerative disorders. The low sensitivity of the epidemiological methodology in detecting low risk associations is probably insufficient to reliably identify any risk to health caused by EMF. Therefore, although epidemiological studies will be needed to ultimately validate the extent of any potential health hazard of EMF, such research must be supplemented and supported by data from animal and in vitro studies. Therefore, in vitro studies using the most modern molecular biological techniques such as. genomics and proteomics are urgently needed in order to create at least a hypothetical basis for the understanding of disease development through EMF-exposure. If it can be determined that such a basis exists, it becomes even more important, to search for marker substances which are specific for EMF exposure. Such marker substances could considerably increase the accuracy of epidemiological studies, so that even a low health risk due to EMF exposure would not escape epidemiological detection.

The main goal of the REFLEX project is to investigate the effects of EMF on single cells in vitro at the molecular level below the energy density reflected by the present safety levels. Most, if not all chronic diseases, including cancer and neurodegenerative disorders, are of diverse and heterogeneous origins. This variability is to a great extent generated by a relatively small number of critical events, such as gene mutations, deregulated cell proliferation and suppressed or exaggerated programmed cell death (apoptosis). Gene mutations, cell proliferation and apoptosis are caused by or result in an altered gene and protein expression profiles. The convergence of these critical events is required for the development of all chronic diseases. The REFLEX project is, therefore, designed to answer the question whether or not any of these disease-causing critical events could occur in living cells after EMF exposure. Failure to observe the key critical events in living cells in vitro after EMF exposure would suggest that further research efforts in this field could be suspended and financial resources should be reallocated for the investigation of more important issues.