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The Cancer Journal - Volume 8, Number 5

review

Can non ionizing radiation induce cancer?

L. Verschaeve

Flemish Institute for Technological Research (VITO), Environment Division,
Boeretang 200, B-2400 Mol, Belgium. Fax.: +32-14-320-372

Key words: RF, radiofrequency fields, ELF, extreme low frequency fields,
non-ionizing radiation, mobile telephone, epidemiology, cancer

INTRODUCTION

The use of electricity has been one of the most important conditions for the
development of present-day society. Now, it is impossible to imagine what
our lives would be like without access to this source of energy. However,
especially since the publication by Wertheimer and Leeper (120) which
reported an association between power lines and cancer in children, the
health risks connected with electromagnetic fields (EMF) in general is
highly debated. At present, despite many epidemiological and laboratory
studies, the EMF-cancer connection remains controversial. Extremely low
frequency fields (ELF) and radiofrequency fields (RF) are of particular
importance. This review paper on the EMF-cancer association will therefore
be restricted to these types of electromagnetic field.

THE ELECTROMAGNETIC SPECTRUM: IONIZING AND NON IONIZING RADIATION

Ionizing and non ionizing radiations are both electromagnetic waves, or
fields that are composed of an electric field and a magnetic field
component. They are characterized by their wavelength, frequency and energy,
which are related to one another. Electromagnetic fields can therefore be
ranked on the so-called electromagnetic spectrum (Figure 1) according to
these characteristics. With a frequency of 50 Hertz (Hz) in Europe, and 60
Hz in the US (1 Hz = 1 cycle per second), power line EMF belong to the
"extremely low frequencies" (0-300 kHz). Radiofrequency fields, including
microwaves, have higher frequencies (300 kHz - 300 GHz), shorter wavelengths
and a greater amount of energy. They also have enough energy to cause
heating in conducting materials. Close to the transmitter, these high
frequency fields may thus be harmful to human beings, which is why, e.g.,
rules for safety distances to radar stations have been laid down. These
"thermal" effects are quite well recognized and understood, but athermal
effects may also be anticipated. Provided they really exist, they may be
more harmful, since they are not directly perceived. X-rays have still
higher frequencies. They are ionizing radiation as they are able to cause
ionization, that is the breaking of molecular bonds, which damage DNA.
This paper deals with non ionizing radiation. This has frequencies below
about. 1015 Hz, wavelengths greater than approximately 30 mmmm, and photon
energies lower than approximately 12.4 eV. This is precisely the reason why
the EMF-cancer connection is highly debated among scientists. Non ionizing
radiations, in essence, have energies that are too low to break even the
weakest chemical bond. It is therefore unlikely that such EMF cause cancer
directly or are mutagenic. There is a general consensus about this, but non
ionizing radiations may be cancer promotors or co-mutagens. Data showing the
presence of a cancer connection are accumulating, and a number of hypothesis
have recently been put forward which may explain the positive results. We
will come to some of them later on. We will first review some of the
relevant data.

EXTREMELY LOW FREQUENCY FIELDS: CANCER INCIDENCE IN THE GENERAL POPULATION

Extremely low frequency fields are characterized by a frequency lower than
300 KHz. The amplitude of the electric field is expressed in terms of
volt/meter (V/m), and the magnetic field amplitude or magnetic flux density
in tesla (T). Most exposures to man-made sources are in the ranges up to 100
kV/m and 20 mT, and include the vast electric power systems present
throughout the industrialized world. Most studies with regard to ELF and the
general population deal with high voltage power lines, but a number of
studies have also been devoted to other exposures, e.g., resulting from the
use of an electrical blanket.
A survey of the literature, starting with the Wertheimer and Leeper (120)
study shows that, at least in a number of the investigations, ther is
evidence suggesting an association between ELF exposure and childhood cancer
and leukemia. In this kind of investigation, most attention is paid to the
magnetic field. This is because epidemiological studies have found
associations between increased cancer risks and power-line configurations,
which are thought to be surrogates for magnetic fields. No such association
have been found with measured electric fields. A summary of some of the most
representative residential power-line cancer studies is given in Table I.
Details of each of the investigations can be found in the original papers.
We here will discuss in more detail a few of the most cited investigations
showing an association between childhood cancer and ELF exposure through
high voltage power lines.
The original Wertheimer and Leeper (120) study showed that children who had
died from cancer were two to three times more likely to have lived within
40m of a high-current power line than were the other children studied.
Exposure to magnetic fields was identified as a possible factor in this
finding. The methodology of this study has been criticized but a more
rigorous study by Savitz et al. (91) on 356 childhood cancer cases from 1976
to 1983 found similar results. Another important investigation was performed
by Feychting and Ahlbom (26, 27). It was conducted on all persons who had
lived on a property located within 300m from any of the 220 and 400 kV power
lines in Sweden from 1965 to 1985. The corridor was so wide that it included
both exposed and unexposed homes. The control population could therefore be
taken from the same region. In particular, a statistically significant
increased risk of childhood leukemia was observed, although somewhat higher
risks were also found for other cancers. The results thus provide support
for the hypothesis that exposure to magnetic fields increases the risk of
childhood leukemia. For brain tumors no association was seen in this
particular study, and for adults there were no statistically significant
results. This study is often considered as one of the most representative
studies performed in so far as it included a population of nearly half a
million people and as it took advantage of one of the best cancer and
population registries in the world. Furthermore, efforts were made to assess
possible effects of other factors that could affect the results of the study
(e.g., air pollution and socio-economic status). No influence of such
"confounders" could be identified. Yet, this study was also confronted with
scepticism as the number of cancer cases remained low (low statistical
power), and because no cancer association was seen with present-day magnetic
field levels measured in the home. The "positive" results were indeed
obtained when the "dosimetry" was based on magnetic field levels presumed to
have existed around the time the cancers were diagnosed. In a similar study
conducted in Denmark (76, 77) 1707 cases of leukemia, brain tumors and
malignant lymphomas were investigated. All cases were recorded in the Danish
cancer registry and were restricted to children of less than 15 years at
diagnosis. Controls were selected at random from the central population
registry. The study revealed that exposure to magnetic fields from
high-tension lines (in the order of 0.4 mmmT) increased the incidence of
cancer. The risk for lymphoma was already increased for fields above 0.1
mmmT. However, as the number of cases was low, the risk estimate is still
uncertain.
Some "positive" findings have been presented here; however, it should be
kept in mind that negative results have also been obtained and that there
are furthermore contradictions within the positive data. Table I, for
example, shows that some investigations demonstrated an association between
leukemia and a residence near high-tension power lines, whereas this
association was missing in other studies which may have demonstrated an
association with other cancer types. It may also be considered rather
puzzling that the increased risk for leukemia found by Feychting and Ahlbom
(27) was only for one-family homes, not for appartment houses. Does this
means that the results are to be interpreted as irrelevant and rather as a
matter of "chance"? This is probably too easy. As a matter of fact,
epidemiological investigations of this kind are faced with a number of
shortcomings that may greatly influence the results. Therefore, each
individual investigation may be considered inconclusive. An overall
evaluation of the investigations may be more valuable. Some of the most
common shortcomings or difficulties are given below.
- With respect to sample size it should be clear that even an investigation
of half a million people will end up with comparing only a few cases of a
particular cancer, possibly with even fewer cases in the controls. They are
rare diseases, after all. This means that even an "odd ratio's" (or relative
risks) of for exemple, 2.0 (a 100% increased risk of having cancer) may not
be statistically significant due to small sample sizes, whereas false
significancies may also be obtained. When many risks are calculated, some
can be "significant" by chance only. Adding up the cases from different
individual studies in a so-called "meta-analysis" should theoretically help
in increasing the statistical power. However, this is usually not possible
because the test subjects and methods for dosimetry may not be comparable,
or the study design as a whole may be very different (e.g., case-control vs.
cohort study). If a meta-analysis is possible, sample sizes and statistical
power often still remain low.
- On the other hand the "dosimetry" may be very approximative and one
"error" or misclassification may (due to the small numbers) be sufficient to
change the outcome of the results. Methods that have been used for exposure
assessment include direct "spot measurements" in the homes, "wiring codes"
(a substitute method to estimate magnetic fields produced by power lines
which is based on the size and number of power-line wires and the distance
between the power lines and the home), "calculations" based on historical
data of average field strengths for each case, etc. As a matter of fact,
even the spot measurements may not be adequate as there is still
disagreement over what should be measured (frequency ranges, harmonics,
continuous, intermittent or transient fields, degree of polarization,
measurements on the front door, in the bed- or living room, peak field
levels, time-weighted averages, etc.). As all investigations so far are
retrospective, there is always some uncertainty about the exposure level.
With the small number of cases this may be a major source of error.
- The influence of confounding factors is also very important. For example,
Savitz et al. (91) found a weak association between the incidence of
childhood leukemia and their living near high-tension lines. However, a
significant association was also found in the same experimental group
between leukemia and residential traffic density (92), or prenatal exposure
to parents' smoking (47). This example illustrates the importance of
confounding factors, but these are usually not taken into consideration
sufficiently.
- According to recent investigations it is now also recognized that there
may be a number of subjects who are hypersensitive to electromagnetic waves.
They exhibit reactions when exposed to particular EMF frequencies that are
comparable to the allergic responses that may occur after exposure to
chemical allergens (e.g., 97, 99, 100).
- Finally, it is worthwhile to note that "positive" findings (association of
EMF exposure and cancer) are often emphasized over "negative" findings
(i.e., publication bias). This may influence the overall risk estimate of
EMF exposure in general.
In conclusion, it may be argued that there indeed exists some
epidemiological evidence for an association between exposure to power-line
EMF and childhood cancer. However, no causal relationship has been
demonstrated so far, only associations. The relative risks are small, as are
the absolute numbers. According to Olsen (77), the present-day exposure
level may be responsible for one extra case of childhood cancer every 5
years in Denmark. Extrapolations from the Feychting and Ahlbom (27) study
suggests that two children per year in Sweden would develop leukemia as a
result of living near power lines. Although there are also a few studies
showing an association between power-line frequencies and adult cancer
(Table I), this is much less evident. More evidence for adult cancer
following exposure to ELF comes from investigations of professionally
exposed subjects.
As already mentioned, not only high-tension power lines may be responsible
for a reported ELF-cancer connection. Pre- and post natal exposures to ELF
from household electrical equipment (e.g., electric blankets) has also been
reported to increase the incidence of cancer, including leukemia,
testicular, breast and brain cancer (57, 93, 106, 113, 114). However,
associations with cancer were again border-line or questionable, and
negative results has also been obtained. Preston-Martin et al. (81)
reported, for example, no effect on acute myeloÜd leukemia and chronic
myeloÜd leukemia rates from electric blanket use. However, as this study was
conducted in California, the use of an electric blanket must be considered
less frequent than in regions where weather is colder.

EXTREMELY LOW FREQUENCY FIELDS : CANCER INCIDENCE IN PROFESSIONALLY EXPOSED
SUBJECTS

The investigations reported in Table I on adult cancer and EMF exposure in
the home environment show no clear association, but the situation is
different when cancer risks for jobs involving work around electrical
equipment are considered. Yet, to date it is not clear whether these risks
are caused by EMF or by other factors. Studies on increased risk in
electrical occupations are difficult to conduct because exposure to many
hazardous chemicals and, e.g., radiofrequency fields, may occur in
electrical and electronic occupations, whereas several non electrical
occupational groups are also exposed to EMF. Therefore, the persons
classified as not exposed may have worked in "exposed" occupations. Thus it
may well be that the relative risk for the case-workers may be higher than
that shown by the results. As for the residential exposure to
electromagnetic fields, dosimetry is again difficult and usually based on
estimates or simply job categories. In domestic environments the strength of
a magnetic field during a 24 h stay rarely exceeds 0.2 mmmT. At work there
are environments with up to 10,000 times higher maximum values. Welding, as
well as jobs in electrically powered locomotives, work on power lines and
jobs in iron and steelworks are examples of "higher than normal" magnetic
field values. Table II gives an overview of some of the most representative
epidemiological investigations on EMF-exposed workers. It should be noted
that some of these studies may include exposure to electromagnetic fields
other than ELF (e.g., microwaves).
As an example, the investigations of Floderus et al. (28, 29) may be cited.
They studied all cases of leukemia and brain tumors occuring during
1984-1987. The relationship with EMF-exposure was the strongest for chronic
lymphatic leukemia. In the most exposed group, with an average exposure in a
working day of over 0.29 mmmT, the risk of developing this form of cancer
was tripled, compared with the control group. The results also clearly show
that the risk (expressed as relative risk) increases with increased exposure
to magnetic fields (Table III). This relationship is statistically
significant. Factors that were considered as possible confounders were the
age of the subjects, benzene, ionizing radiations, solvents, pesticides and
smoking. They did not influence the results. A French-Canadian study
conducted by Thâriault et al. (107) of men who had worked for over 10 years
for three utilities and who had been exposed to an average magnetic field of
>0.2 mmmT found that these men were more than twice as much at risk of acute
non lymphoÜd leukemia and acute myeloÜd leukemia than those with lower
exposures. Workers who had the greatest exposure to magnetic fields had 12
times the expected rate of astrocytomas. Clear dose-response relationships
were not observed, and the results were not consistent across the three
utilities in the study. Estimates of each man's cumulative magnetic field
exposure was, among other things, based on measurements of current exposure
of other workers performing tasks similar to those in the cohorts using
personal dosimetry. No association with magnetic fields was found for any of
the other 29 types of cancer studied. When known confounders were controlled
for there was no change in the results. In a study of two of the three
utilities studied by Thâriault et al. (107), Armstrong and colleages (5)
found no association between pulsed EMF and leukemia, but an unexpected
association with lung cancer was reported.
Annual incidence of breast (mammary) cancer among women is about 1 in 1000.
Male breast cancer is far less common. Association of increased risk for
rare cancers with a specific agent or factor can lend strength to the
hypothesis that the agent may be a carcinogen, provided certain criteria for
causality are met (117). Therefore, male breast cancer has been of
particular interest to epidemiologists. Table II shows a number of
investigations where an increased risk for male breast cancer was indeed
found in electrical occupations. EMF exposure was also found to increase the
risk for breast cancer in women. Loomis et al. (58) and Cantor et al. (12)
found that women in traditional electrical occupations had a higher but
statistically non significant mortality risk from breast cancer compared to
women in occupations without high exposure to EMF. The risk for malignant
melanoma was also found to be greater in electrically exposed workers
compared to non exposed controls. It was, however, pointed out that
excessive melanoma in electronics and telecommunication workers may be a
consequence of their generally higher socio-economic status. These subjects
are usually also exposed to more than ELF alone.

RADIOFREQUENCY (RF) FIELDS, MICROWAVES (MW) AND MOBILE COMMUNICATION

Extremely low frequency fields are one of the important non ionizing
radiations with regard to human exposure and risk assessment. Radiofrequency
fields, and especially microwaves (300 MHz - 300 GHz) are another very
important part of the electromagnetic spectrum in this respect. While in the
past decade people were especially concerned about the safety of microwave
ovens (2450 MHz) and, before that, radar equipment, it is wireless
communications (e.g., mobile telephones) which are particularly considered
at present. It is now generally accepted that modern microwave ovens are
harmless (leakage of microwaves is insignificant), at least when properly
used, whereas a number of investigations on radar operators has identified
some "thermal" effects that lead to safety precautions minimizing the
hazards. But little is known about the health hazards of cellular
telephones, which are rapidly gaining popularity. Cellular phones include
car telephones, where the telephone body is mounted inside the car and the
antenna is mounted on the outside of the vehicle; portable telephones, with
the antenna and telephone body carried in a case separate from the handset,
and self-contained portable telephones, in which the handset contains the
power source as well as the antenna. Industry forecasts estimate that,
within a decade, cellular communication devices will be used by over 60
million people in the US alone. While cellular communication technology has
been rapidly advancing, there have been few scientific studies of this new
technology and there is very limited information on whether the radiation
emitted by cellular phones poses a risk to human health. There exist only a
few epidemiological studies, comparable to the ones discussed above for ELF
electromagnetic fields, in which the cancer incidence in RF-exposed subjects
was investigated. In a study conducted by Robinette et al. (85) on naval
personnel and radar operators it was shown that workers in this occupation
had a higher than normal risk for brain cancer. Mortality from cancer was
increased close to air force bases compared with other places. It was
concluded that this was due to the proximity of radar installations (54).
This study was criticized (80) on the grounds of fautly data collection,
whereas other criticisms could be the absence of physical measurements and
the omission to investigate potential confounders. A possible association
between chronic exposure to microwaves and polycythemia was mentioned in a
letter to the New England Journal of Medicine (31), but this was not based
on an extensive investigation. It was also reported that amateur radio
operators die from myeloÜd leukemia more often than other subjects (74), but
this observation was subject to the same criticisms as above. A short
communication also reported a cluster of 6 cases of testicular cancer in a
cohort of 340 American policemen over a 12-year period (20). This is about 7
times the expected number and according to the authors, the real risk may
even be higher. All six were regularly exposed to hand-held speedmeters
operating through radar waves. Known risk factors for testicular cancer did
not apply to these men.
To date, there have been no complete epidemiological studies which examine
the risk of cancer from cellular technology. There have been some lawsuits
launched in the US alleging that some person's brain tumor was a result of
cellular phone use (e.g., 24) but none of these cases brought forward any
evidence other than the anecdotal history of the subject's mobile telephone
usage. At present, a number of studies have been undertaken to explore the
relationship between exposure to radio-frequency radiation and brain or
female breast cancer, but the results of most of these studies are several
years away.
A number of efforts have also been undertaken to investigate biological
effects of EMF under laboratory conditions. However, once more, the study
design was not always adequate and the experiments were very often
unsufficiently controlled. Nevertheless, it is possible to draw a number of
(preliminary) conclusions from the literature.

ELF FIELDS: LABORATORY INVESTIGATION

A large number of studies have been carried out, but, as for the
epidemiological studies and as for other non ionizing radiations, many are
subject to criticism because of a number of methodological shortcomings,
including the initial difficulty in recognizing all parameters relevant to
biological models, field characteristics and exposure conditions. Many
results must also be taken with caution because of the existence of
so-called "window effects"; that is, the fact that biological effects may
strictly be dependent on specific combinations of frequency and/or field
strength. Effects have been found on several cell functions and phenomena. A
non exhaustive list is given in Table IV. Here, we will restrict ourselves
to a number of general observations relevant to the cancer problem and for
which there exists sufficient scientific background.

Calcium transport - Calcium is essential for many cellular functions,
especially for transmission of extracellular signals, the regulation of
intracellular transport of compounds, the release of secretion products,
bone metabolism, muscle contraction, etc. Maintaining an optimal cellular
calcium concentration is therefore of key importance. This is for example
obtained by a number of very precise active ion transport mechanisms through
cell membranes. Many investigations, mostly in vitro, have shown that ELF
fields influence calcium release from cells (e.g. 10). This effect is highly
dependent on the frequency and was one of the first observed examples of a
window effect.

Intercellular communication - Electrical and chemical signals through
membranes are responsible for intercellular communication. It has been
repeatedly suggested that ELF fields (and other non ionizing radiations) may
interfere with the intercellular information transfer (30, 38), which also
may explain the existence of a window effect.

Effects on the genetic material - ELF fields are, according to a number of
in-vitro studies, unable to induce chromosomal aberrations in white blood
cells as measured by the analysis of sister chromatid exchanges (15, 86).
However, it should be noted that sister chromatid exchanges are much better
indicators of genetic effects induced by chemicals than by ionizing (25) and
also non-ionizing radiation (62). Therefore, more sensitive methods should
be used in order to detect this kind of effect. A significant increase in
DNA synthesis was sometimes observed (54) as well as an increase in cell
division and transcriptional activity (39, 55).

Hormonal effects - It has been demonstrated in several studies that a
decrease in melatonin synthesis and secretion by the pineal gland is
associated with an increased cancer risk. Experimental evidence indicates
that an increase in melatonin may reduce the levels of estrogen, which are
thought to play an important role in the induction of breast cancer.
Melatonin is, furthermore, the most potent anti-oxidant and free radical
scavenger known to date (84). As oxidative stress is known to play an
important role in cancer initiation, promotion and progression,
environmental factors that reduce the level of anti-oxidants may indirectly
favor cancer development. Exposing rats to 50-60 Hz fields up to 130 kV/m
has been reported to reduce or delay circadian increases in noctural pineal
N-acetyltransferase activity and melatonin levels in sexually immature (83)
and mature rats (124, 125, 126). ELF fields are therefore suspected of
inducing, among others, breast cancers (101).

Interactions with the immune system - Some investigations have demonstrated
that ELF fields are able to decrease natural killer-type cytotoxicity of
lymphocytes (60, 61, 79). In a study of chemically induced skin tumors in
mice exposed to 60-Hz magnetic fields at 2 mT no acceleration of tumor
growth related to magnetic field exposure was detectable, but in some of the
animals symptoms of suppression of NK cytotoxicity activity were found (72).

Other cancer-related studies - A number of in-vitro investigations of the
effects of ELF-modulated microwaves have been performed, with results
suggesting a promoting potency of EMF in the cellular process of
carcinogenesis. They are mentioned below (RF fields: laboratory
investigations).

RF FIELDS: LABORATORY INVESTIGATIONS

Alternating electromagnetic fields produce electrical fields and current in
tissue. When the frequency is increased to more than 100 kHz, the cell
membrane gradually loses its isolation capacity. The energy that is
dispersed in the cell is dependent upon the frequency and the strength of
the field as well as cellular properties, among other things. Molecular
vibration of water molecules, or changes in molecules produce increased
kinetic energy which in turn produces measurable effects that can result in
a series of cellular functions and/or a rise in temperature. Radiofrequency
fields are therefore known to produce so-called thermal effects. Therefore,
RF fields have some unquestionable effects (for example cataract; e.g., 14,
45). The tissue characteristics (e.g., water content, permeability and
permitivity) and thermoregulation properties (blood flow, etc.) determine
the vulnerability of the tissue (eyes are very vulnerable). These, and other
thermal effects are beyond the scope of this paper and thus will not be
discussed here. Due to thermal effects, the notion of dose is different for
RF fields and for ELF fields. There is a general consensus that the average
power density in the tissue is the most significant parameter. This is
usually known as the SAR or Specific Absorption Rate, a quantity properly
averaged in time and space. SAR values are expressed in Watts per kilogram
(W/kg). Many guidelines for RF radiation exposures use the average SAR value
over the whole body but this is usually unsufficient, as SAR values may be
locally very different from the body average. It is presently considered
that there are no observable adverse health effects for SAR values lower
than 4 W/kg. Guidelines or norms therefore accept exposure levels above 0.4
W/kg (safety factor) whole body. However, local SAR values may be higher. As
an example, one may mention the portable phone which emits high frequency
energy from the antenna. Up to 50% of its energy may be partially absorbed
in the nearby tissues (in the head of the user). The actual amount absorbed
depends mainly on the proximity of the antenna and handset from the head of
the user. A GSM (Global System for Mobile communication) phone has a peak
output of 2W. With a duty factor of 1/8 (switched "on" one second every
eight seconds) this leads to a time average of 0.25W output leaving the
antenna. The maximum power absorbed is thus of the order of one tenth of a
Watt. This may seem a very small value, but as the deposition is very local
the absorbed power per unit of mass may be substantial. It has been shown
that under "worst-case situations" the recommended maximum value of exposure
(e.g., 1.6 W/kg) is clearly surpassed (4) (During the last decades several
countries and organizations have recognized the importance of safety
requirements in the field of electromagnetic energy. To date there exist
several guidelines, norms and standards, all based on thermal
considerations. Most standards and norms recommend a relatively small volume
with a weight of a few grams, over which SAR should be averaged. Since it is
assumed that a very short exposure time is harmless, most norms mention an
averaging time, typically 6 minutes).
Besides thermal effects (occuring at power densities > 10 mW/cm2) RF fields
may also induce athermal effects. Athermal effects are not yet taken into
consideration for the establishment of guidelines or norms because there is
still too much discussion and too little real scientific evidence about
their presence and significance. Yet, they are, if present, usually thought
to be responsible for, e.g., cancer induction although cancer may also have
a "thermal" origin. One of our challenges is therefore to understand how RF
energy gets into tissue, how it is distributed and for how long it is there,
especially in low-exposure situations where the temperature is not
measurably increased, and finally what the consequences are. Many laboratory
investigations are now being conducted for this purpose. We again refer to
Table IV for a list of domains in which biological effects have been
ascribed to ELF and RF fields. We here will only consider some of the data
that are relevant for cancer research. Yet, it should be stressed that the
majority of the experiments were conducted under thermal exposure conditions
which may invalidate a considerable part of the results, as they sometimes
concern extreme situations not encountered in real life. In many instances
it was not even clear whether the exposure conditions were thermal or
athermal. It should furthermore be kept in mind that radiofrequency fields
cover a wide frequency range and that results obtained for, e.g., the
microwave oven frequency of 2450 MHz does not allow a prediction of effects
from a GSM mobile telephone (900 MHz band) or for DCS and DECT wireless
telecommunication systems that are operating in the 1800 MHz band (DCS:
Digital personal Communication System; and DECT: Digital European Cordless
Telecommunciation). Most experiments were devoted to frequency fields
exceeding 1000 MHz, with 2450 MHz being most often applied. Results can be
affected by ambient temperature, humidity and prevailing air current,
whereas thermal effects on animals are also affected by the size of the
animal and by the local blood supply. Also the orientation of the animal
with respect to the EMF source and its morphology may be determinant factors
accounting for the results obtained. It is therefore extremely difficult to
extrapolate results from animal tests to humans. Finally, the radiofrequency
field is sometimes utilized with a strength that alternates with a low
frequency, e.g., ELF. This is described as a high frequency carrier wave and
a low frequency modulation. The effect of the RF component can thus be
difficult to distinguish from the effect of the low frequency component. The
short overview of data presented below will therefore only be indicative for
possible RF effects and directions for future research.

Genetic effects - In-vitro investigations of Kerbacher et al. (49) and Meltz
(73) on different cell systems provided evidence for a lack of direct
genotoxic and mutagenic effects of continuous and pulsed microwaves at
different power densities. Additionally, no synergistic effect was found
between the applied field and mitomycin C, adriamycin and proflavin.
Ciaravino et al. (13) also found no synergistic effect between
moderate-power-radio-frequency electromagnetic radiation and adriamycin on
cell-cycle progression and sister chromatid exchanges. However, a
synergistic effect was found with mitomycin C in a recent investigation of
954 MHz waves emitted by the antenna of a GSM base station (64, 115).
Indeed, a very reproducible increase in the frequency of mitomycin C-induced
sister chromatid exchanges was found in human lymphocytes when the blood was
first exposed to the microwaves (15W power density, SAR=1.5 W/kg). It was
also shown that the microwaves alone may have a certain clastogenic
(chromosome breaking) effect, but only in very precise circumstances of
exposure (63). This effect was also studied for exposures to 450 MHz fields
from a mobile telephone but the results were not very clear (Maes et al.,
unpublished data). No effect was found in a limited sample of maintenance
workers professionally exposed to microwaves of different frequencies (63).
An increased frequency of chromosome aberrations was also found in in-vitro
experiments involving other cell types, microwave frequencies and
cytogenetic endpoints (e.g.19, 35, 36, 53, 62). Also in vivo, changes in
metaphase counts and translocation numbers were observed even at low
exposure levels. This was found in Balb/c mice that were exposed for two
weeks to pulsed 9400 MHz microwaves, one hour a day for 5 days a week (67).
In male CBA/CAY mice exposed to 2450 MHz microwaves increased chromosome
exchanges and other cytogenetic abnormalities were found in germ cells
exposed as spermatocytes (68). However, negative results were also found in
other investigations in somatic cells (e.g., 46) as well as in germ cells
(e.g., 8, 89). Using the alkaline comet assay, which is a sensitive method
for assessing DNA single-strand breaks and/or alkali-labile sites in DNA,
DNA damage was found in lymphocytes exposed to 954 MHz waves (115) and in
brain cells from rats being exposed in vivo to 2450 MHz waves at SAR values
of 0.6 and 1.2 W/kg (52). The latter may be of particular importance with
regard to the possible, but to date totally unproven, association between
microwaves (mobile telephones) and brain cancer. In a short pilot experiment
in which "comets" were investigated in white blood cells of rats, no
clear-cut effect could be ascribed to a 954 MHz microwave exposure over
several weeks (115). According to the above (and other) cytogenetic
investigations it is clear that caution must be exercised in making any
general conclusion on the clastogenicity of radiofrequency fields and
microwaves in general.

Cancer-related studies - According to a series of papers, low level
Hz-modulated microwave radiation may affect intracellular activities of
enzymes involved in neoplastic promotion without measurable influence on the
overall DNA synthesis. Byus et al. (11) reported, for example, evidence of
an effect on intracellular levels of ornithine decarboxylase (ODC) which is
an enzyme implicated in tumor promotion. Tumor promotors increase ODC
synthesis, as do the microwaves. These effects were noted only for certain
modulations of the carrier wave, again illustrating the "window effect".
Balcer-Kubiczek and Harrison (6) exposed cells to 120-Hz-modulated
microwaves (SAR from 0.1 to 4.4 W/kg) followed by treatment with a phorbol
ester tumor promoter. Cell transformation was induced in a dose-dependent
way (increasing with increasing SAR value). Lymphocyte transformation was
another observation after exposure of the cells to pulsed or continous
radiofrequency radiations (17, 102). Pulsed RF fields were found to be more
efficient than continuous waves in eliciting this type of effect. These
effects may possibly be thermal in nature. Still another interesting
observation was that of Adey (3) who reported that 120-Hz-modulated 450 MHz
microwaves inhibit gap junction cell-to-cell communication in cultured
hamster ovary cells.
The above investigations were performed in vitro; however, a number of in
vivo investigations have also been performed. Of particular interest is the
study conducted by Szmigielski et al. (103) who observed faster development
of benzo-a-pyrene induced skin tumors in mice that were exposed for some
months to subthermal 2450 MHz microwaves. Also very interesting is the study
of Guy et al. (43) who exposed 100 rats from 2 to 27 months of age to
pulsed-microwaves (0.4 W/kg). The exposed group had a significant increase
in primary malignant lesions compared to the control group when lesions were
pooled regardless of their location in the body. In another study, the
effects of EMF exposure in a rat brain glioma model was investigated (88).
The exposure consisted of 915 MHz microwaves, both as continuous waves (1W)
and modulated with 4, 8, 16 and 200 Hz in 0.5 ms pulses and 50 Hz in 6 ms
pulses (2W per pulse). Exposure was daily from the fifth day after the start
of tumour growth in the rat brain until the death of the animal which by
then had a large brain tumour. The results did not support the suggestion
that even an extensive daily exposure to EMF causes tumour promotion.

Hormonal effects - As for ELF fields, microwaves were shown to influence the
concentration of some hormones, including melatonin, in the blood. In this
particular case, a thermal effect influencing endocrine glands is
anticipated (65).

Endocrine and immune systems - Most of the described effects on the
endocrine system can be related to the nonspecific stress induced by an
increase in body temperature. Chronic exposures have yielded transient
changes in immunological parameters such as the response of B- and
T-lymphocytes to mitogens (43). Specific athermal effects were also observed
depending on the modulation characteristics of the radiofrequency radiation.
Changes in the humoral response of mice were, for example, observed by
Veyret et al. (116) after a 5-day exposure to low-level 9400 MHz microwaves
amplitude-modulated at around 20 MHz.

Membrane effects - There have been a number of reports on enhanced calcium
efflux using ELF-modulated microwaves, but it was also demonstrated that the
important component was the ELF signal and not the carrier wave. However,
investigations on acetylcholinesterase activity using the same types of
radiofrequency radiation might be related to calcium transport (21). Some
studies confirmed alterations of membrane transport of ions and transient
inhibition of energy-delivering systems by microwaves (for review, see 90),
whereas Phelan et al. (78) observed a shift from a more fluid to a more
solid and ordered state of the membrane in melanin-containing cells after
low-level pulsed 2450 MHz microwave exposure at a SAR of 0.2 W/kg. This
modification of membrane fluidity seems to be unique to melatonic membranes
and seems also to be related to the generation of oxygen free radicals,
which is considered to be one of the established risk factors in the
development of neoplasms. Finally, an effect of low power 10750-MHz
microwaves on the functioning of acetylcholine receptors was also observed
(104). It was shown that the frequency of opening of these ion channels
decreased during exposure. The relevance of most of these membrane effects
for human health remain unclear.

Cytotoxicity of T-lymphocytes - Mouse T-lymphocyte cytotoxicity was
suppressed during exposure to 450-MHz microwaves modulated at frequencies
between 3 and 100 Hz. Non modulated fields had no effect (60). The effects
observed may thus be due to ELF exposure rather than to the microwaves.

Growth inhibition - A large number of experiments were initially performed
in the Soviet Union on growth inhibition of micro-organisms under microwave
exposure. The results usually show specific "resonance" effects (e.g. 9).
Resonances between 41640 and 41790 MHz were found in yeast (40, 41). Because
lichens are extremely sensitive to environmental pollution their growth was
also investigated for assessing effects of 2450 MHz microwaves at different
power densities. Power densities of 50 mW/m2 had growth inhibiting
properties, however, it was assumed that the effect was thermal, causing
increased respiration and inhibited growth for this reason (23).

MECHANISMS OF ACTION

Suggestive evidence for biological effects of electromagnetic fields, and
especially in relation to cancer has been given in the previous pages.
Although the link between electromagnetic fields and carcinogenesis remains
uncertain there is a growing body of data from studies indicating that ELF
and RF fields interact with various biological systems at energy levels
significantly lower than those needed for the stimulation of excitable
tissues or for thermal interactions (1, 105, 122). Several mechanisms of
interaction with biological tissue have been hypothesized but they still
need further development and testing. Some of the hypothesis are given
below. Although they are sometimes described only for ELF or RF, they are
usually valid for EMF in general.

INTERACTIONS WITH CELL MEMBRANES

Pericellular currents induced by electromagnetic fields are sensed by
intramembrane receptor proteins which amplify the signal and transfer it to
intracellular enzyme systems and to the cell nucleus. They may produce
intracellular alterations (1, 3). With regard to cancer it may for example
be hypothesized that particular membrane receptors can be liberated by the
induced current which may activate corresponding oncogenes (7). Research on
the effects of low-level microwave irradiation on neurochemical changes in
the rat brain has generated theories of activation of endogenous opioids,
which in turn cause a decrease in cholinergic activity in the hippocampus
and the frontal cortex (51). This hypothesis assumes that cell membranes are
primary sites of ELF-mediated cellular responses. As a matter of fact, this
sounds very logical as the intercellular fluid forms a preferred pathway for
electric current flow throughout the tissues. Electrical currents generated
in the body by the application of ELF do not penetrate cells due to the
electrical resistivity of cell membranes.
That the field intensities induced in biological systems which are able
produce these effects are lower than those associated with thermal noise,
may not be considered to refute the hypothesis, as it has been shown that
induced fields of the order of 0.1-0.01 V/m (and sometimes even much smaller
fields) are detectable above the broad-band noise level (119).
Other models involving magnetic field-induced molecular changes in membranes
have been proposed. The basic premise is that the cell membrane exists in a
metastable, non equilibrium state that can be perturbed by weak stimuli. The
stored energy is released by the process as metabolic chemical energy
through the activation of ion pumps or enzymatic reactions within the
membrane (1, 2, 32, 33).

FREE RADICAL FORMATION AND OXIDATIVE STRESS

It is known that ionizing radiation can damage DNA directly, but also
indirectly by formation of free hydroxyl radicals that may interact with DNA
(44). Non ionizing radiations are not able to damage DNA directly, but,
according to a recent hypothesis, an indirect DNA damaging activity is
possible (95). Normal metabolic processes produce oxidants that may be
neutralized by anti-oxidants. Oxidative stress occurs only when there is an
imbalance (due to inadequate nutrition or exposure to environmental
pollutants) with an excess of oxidants. It is known that they can play an
important role in cancer initiation, promotion and progression. According to
the hypothesis, interaction of non-ionizing radiations with tissue may
induce such an imbalance (increased amount of free radicals, and the
breakdown of anti-oxidants). The "melatonin effect" reported earlier may
also be seen in this context. Addition of a minimal amount of energy through
application of a low magnetic field from ELF or RF origin may be sufficient
to disrupt the oxidant/anti-oxidant equilibrium, favorizing oxidants.

MAGNETOSOMES IN THE BRAIN

All living organisms are essentially made of diamagnetic organic compounds,
but some paramagnetic molecules (e.g., O2) and ferromagnetic microstructures
(hemoglobin core, magnetite) are also present. Magnetite crystals
(magnetosomes, Fe3O4) were found in many organisms (118) and may, at least
partially, explain the remarkable orientation capacity that is
characteristic for many of them (e.g., magnetotactic bacteria, some
termites, sharks, eels, bees, pigeons, etc.). It was shown that the human
brain also contains magnetosomes (50). These microstructures behave like
small magnets and may be influenced by external electromagnetic fields
changing their energy content, which finally results in a mechanical force
with, for example, effects on the hypothalamus and repercussions on immune
and neuroendocrine functions. This may result in a number of effects as the
lowering of natural antineoplastic resistance in subjects exposed to EMF or
have many other effects favorizing cancer initiation, promotion and
progression.

RESONANCE PHENOMENA AND SYNCHRONISATION OF ENDOGENEOUS OSCILLATORS

Resonance phenomena that occur when the wave frequency of the field
coincides with natural vibrations in the cell structures or tissue can
explain a number of cellular changes.
Living organisms possess so-called endogeneous oscillators. Indeed, many
receptors, neurones, muscles and other cell types are characterized by
rythmic fluctuations of information vectors (e.g., cAMP), substrate
infiltrations (e.g., glycolyse) and ion conductivity (e.g., Ca2+, K+). Many
processess are regulated by oscillating neural networks located in specific
centra, for example in the hippocampus, thalamus, medulla oblongate, pineal
gland, baroreceptors and hypothalamus. These oscillators act upon membrane
potentials, switching "on" or "off" a particular stimulation (e.g., release
of a neurotransmitter). These oscillatory centers may absorb exogeneous low-
and high-frequency EM waves and acquire another oscillation frequency.
Neurons that have been modified will consequently synchronize other
downstream neurons in the same way. It should be noted that this external
synchronisation remains present after removal of the external stimulus (EM
field); in other words, the organisms will now function according to the new
frequency of oscillation (98, 118). This hypothesis has already been
verified experimentally (18).

THERMAL EFFECTS

When the temperature of an animal is increased by up to 1 C after
radiofrequency field irradiation, there is a thermally induced stress that
initiates a chain reaction from the hypothalamus to the cortex of the
adrenal gland via the pituitary gland. Hormones are then released from the
adrenal cortex into the blood and in turn cause changes in the blood-forming
and immunological activities. They may create particular cancer-prone
situations. The RF fields emitted by mobile telephones are, however, not
able to create high enough field strengths to give such an effect.

CONCLUSION

Overall, the available human data on EMF and cancer (especially leukemia,
brain and breast cancer) are too inconsistent to establish a
cause-and-effect relationship, but there is enough evidence of association
to raise concern. As a matter of fact, epidemiology has seen a large number
of examples where health hazards were initially described with unconvincing
and sometimes inadequate experiments which demonstrated a weak association
with a given environmental influence. Such associations were found between
cholera and drinking water containing fecal contaminants, between smoking
and lung cancer or between exposure to vinyl chloride and certain forms of liver cancer. All these associations were highly questioned in the past and
are now well recognized.
The present data are thus inadequate for drawing any unequivocal conclusion
as to whether EMF in general, and high-tension power lines and cellular
phones in particular, present a public health risk, especially with regard
to cancer, or not. The available information only allows ELF EMF to be
classed as possible carcinogens for humans, with a higher probability in
occupational exposures. With regard to RF and cellular phones, some animal
studies indicate that they may, when combined with a known carcinogenic
factor, increase the incidence of tumors and tumor growth. This "promotor
effect" may, for example, be due to the local effects of the field that
cause impaired immunocompetence. No epidemiological studies have so far been
conducted on users of cellular phones, but some investigations on RF-exposed
workers (also exposed to ELF) give some weak evidence of association with an
elevated cancer risk. However, if EMF do cause an increased cancer risk,
this risk is only modest and it is unlikely that epidemiology alone will be
able to clearly establish such an effect. Understanding the biological
effects of EMF and the operating mechanisms of action are therefore of
crucial importance. Further, rigorously controlled laboratory investigations
should therefore be encouraged. However, it should be kept in mind that it
will never be possible to prove, either through experiments or through
observations on humans, that a given factor is not carcinogenic. Such a
problem is especially relevant to the question of whether exposure to EMF
cause cancer in humans. Furthermore, the incidence of the disease, the fact
that it can occur spontaneously or be induced by many different
environmental factors, the statistical fluctuations in incidence within
small groups of people and the still unresolved question about cancer causes
and development, suggest that no definite answer will emerge in the
foreseeable future.

REFERENCES

1. Adey WR. Tissue interactions with non-ionizing electromagnetic fields.
Physiol Rev. 61, 435-514, 1981.

2. Adey WR. Some fundamental aspects of biological effects of extremely low
frequency (ELF). In: Biological Effects and Dosimetry of Non-Ionizing
Radiation. (Grandolfo M, Michaelson SM, Rindi A, eds.) Plenum Press, New
York, London, 561-580, 1983.

3. Adey WR. Non linear electrodynamics in cell membrane transductive
coupling. In: Membrane Transport and Information Storage. Alan Liss, New
York, 1-27, 1990.

4. Andersen JB, Johansen C, Pedersen G et al. On the possible health effects
related to GSM and DECT transmissions. A tutorial study. Center for
Personkomminikation, Institute of Electronic Systems, Aalborg University,
Denmark, 1995.

5. Armstrong B, Thâriault G, Guânel P et al. Association between exposure to
pulsed electromagnetic fields and cancer in electric utility workers in
Quebec, Canada, and France. Am J Epidemiol. 140, 805-820, 1994.

6. Balcer-Kubiczek EK, Harrison GH. Induction of neoplastic transformation
in C3H/10T1/2 cells by 2.45 GHz microwaves and phorbol ester Radiat Res.
117, 531-537, 1989.

7. Becker RO, Selden G. The Body Electric. William Morrow, New York, (1988).

8. Beechey CV, Brooker D, Dowalczuk CI et al. Cytogenetic effects of
microwave irradiation on male germ cells of the mouse. Int J Radiat Biol.
50, 909-918, 1986.

9. Berteaud AJ, Dardalhon M, Rebeyrotte N et al. Action d'un rayonnement
âlectromagnâtique É onde millimâtrique sur la croissance bactârienne. CR
Acad Sci. Paris 281D, 843-844, 1975.

10. Blackman CF, Benane SG, Elliott DJ et al. Influence of electromagnetic
fields on the efflux of calcium ions from brain tissue in vitro: a
three-model analysis consistent with the frequency response up to 510 Hz.
Bioelectromagnetics 9, 215-227, 1988.

11. Byus CV, Kartum K, Pieper S et al. Increased ornithine decarboxylase
activity in cultured cells exposed to low energy modulated microwave fields
and phorbol ester tumor promoters. Cancer Res. 48, 4222-4226, 1988.

12. Cantor KP, Dosemici M, Brinton LA et al. Correspondence: Breast cancer
mortality among female electrical workers in the United States. J Natl
Cancer Inst. 87, 227-228, 1995.

13. Ciaravino V, Meltz ML, Erwin DN. Absence of a synergistic effect between
moderate-power radiofrequency electromagnetic radiation and adriamycin on
cell-cyle progression and sister chromatid exchange. Bioelectromagnetics 12,
289-298, 1991.

14. Cleary SF, Pasternack BS, Beebe GW. Cataract incidence in radar workers.
Arch Environ Health 11, 179-182, 1965.

15. Cohen MM, Kunska A, Astemborski JA et al. The effect of low-level 6O-Hz
electromagnetic fields on human lymphoblastoid cells. II. Sister-chromatid
exchanges in peripheral blood lymphocytes and lymphoblastoÜd cell lines.
Mutation Res. 172, 177-184, 1985.

16. Coleman MP, Bell CMJ, Taylor HL et al. Leukaemia and residence near
electricity transmission equipment: a case-control study. Brit J Cancer 60,
793-798, 1989.

17. Czerska EM, Elson EC, Davis CC et al. Effects of continuous and pulsed
2450 MHz radiation on spontaneous lymphoblastoid transformation of human
lymphocytes in vitro. Bioelectromagnetics 13, 247-257, 1992.

18. Danilov VI., Parshintsev VV., Turkin VV. (1984) Influence of a single
pulse of magnetic field on the electrical activity of mollusc neurones.
Biofyzika 29, 109-112.

19. d'Ambrosio G., Lioi MB., Massa R., Scarfi MR., Zeni O. (1992)
Genotoxicity of microwaves. Abs 1st World Congress on Electricity and
Magnetism in Biology and Medicine, Orlando, p 59.

20. Davis RL, Mostofi FK. Cluster of testicular cancer in police officers
exposed to hand held radar. Am J Ind Med. 24, 231-233, 1993.

21. Dutta SK, Das K, Ghosh B et al. Dose dependence of acetylcholinesterase
activity in neuroblastoma cells exposed to modulated radio-frequency
electromagnetic radiation. Bioelectromagnetics 13, 317-322, 1992).

22. EBC. The European Bioelectromagnetics Center. EBC Project. The European
Bioelectromagnetics Association, p 211, 1993.

23. Eicher B, Siegenthaler J, Urech M et al. Effects of microwave and RF
exposure on lichens. Abs XVIth Annual Meeting of the Bioelectromagnetics
Society, Copenhagen, 4, 1994.

24. Elmer-Dewit P. Dialing "P" for panic. Time Magazine, Feb 8, 42, 1993.

25. Evans HJ. Molecular mechanisms in the induction of chromosome
aberrations. In: Scott D, Bridges BA, Sobels FH, eds, Progress in Genetic
Toxicology, Elsevier, Amsterdam, 57-74, 1977.

26. Feychting M and Ahlbom A Magnetic fields and cancer in people residing
near Swedish high-voltage power lines. Institute of Environmental Medicine,
Karolinska Institute, Stockholm, 1992.

27. Feychting M and Ahlbom A. Magnetic fields and cancer in children
residing near Swedish high-voltage power lines. Am J Epidemiol. 138,
467-481, 1993).

28. Floderus B, Persson T, Stenlund C et al. Occupational exposure to
electromagnetic fields in relation to leukemia and brain tumors. A
case-control study. National Institute of Occupational Health, Solna, 1992.

29. Floderus B M, Wennberg A, st A et al. Occupational exposure to
electromagnetic fields in relation to leukemia and brain tumors. A
case-control study in Sweden. Cancer Causes and Control 4, 465-476, 1992.

30. Frey AH. Is a toxicological model appropriate as a guide for biological
research with electromagnetic fields? J Bioelectricity 9, 233-234, 1990.

31. Friedman HL. Are chronic exposure to microwaves and polycythemia
associated? N Engl J Med. 304, 357-358, 1981.

32. Fr"hlich H. Long-range coherence and energy storage in biological
systems. Int J Quant Chem. 2, 641-649, 1968.

33. Fr"hlich H. Possibilities of long- and short-range electric interactions
with biological systems. Neurosci Res Prog Bull. 15, 67-72, 1977.

34. Fulton JP, Cobb S, Preble L et al. Electrical wiring configurations and
childhood leukemia in Rhode Island. Am J Epidemiol. 111, 292-296, 1980.

35. Garaj-Vrhovac V, Horvat D, Koren Z. The effect of microwave radiation on
the cell genome. Mutation Res. 243, 87-93, 1990.

36. Garaj-Vrhovac V, Horvat D, Koren Z. The relationship between
colony-forming ability, chromosome aberrations and incidence of micronuclei
in V79 Chinese hamster cells exposed to microwave radiation. Mutation Res.
263, 143-149, 1991.

37. Gezondheidsraad. Extreem laagfrequente electromagnetische velden en
gezondheid. Den Haag: Gezondheidsraad, 1992, publication nr 92/07.

38. Goldberg RB, Creasey WA. A review of cancer induction by extremely low
frequency electromagnetic fields - is there a plausible mechanism? Med
Hypotheses 35, 265-274, 1991.

39. Goodman R, Abbott J, Henderson AS. Transcriptional patterns in the X
chromosome of Sciara Coprophila following exposure to magnetic fields.
Bioelectromagnetics 8, 1-7, 1989.

40. Grundler W, Keilmann F Sharp resonances in yeast growth prove nonthermal
sensitivity to microwaves. Phys Rev Lett. 51, 1214-1216, 1983.

41. Grundler W, Keilmann F. Resonant microwave effect on locally fixed yeast
microcolonies. Z Naturforsch. (C) 44, 863-866, 1989.

42. Guânel P, Raskmark P, Andersen JB et al. Incidence of cancer in persons
with occupational exposure to electromagnetic fields in Denmark. Brit J Ind
Med. 50, 758-764, 1993.

43. Guy AW, Chou C-K, Kunz LL et al. Effects of long-term low-level
radiofrequency radiation exposure on rats. Vol. 9. Summary, Texas, Brooks
Air Force Base, USAF School of Aerospace Medicine (USFSAM-TR-85-11), 1985.

44. Hall EJ. Radiobiology for the radiologist. JB Lipincott Company,
Philadelphia, 1988.

45. Hollows FC, Douglas JB. Microwave cataract in radiolinemen and controls.
Lancet ii, 406-407, 1984.

46. Huang AT, Engle ME, Elder JA et al. The effect of microwave radiation
(2450 MHz) on the morphology and chromosomes of lymphocytes. Radio Sci. 12,
173-177, 1977.

47. John EM, Savitz DA, Sandler DP. Prenatal exposure to parents' smoking
and childhood cancer. Am J Epidemiol. 113, 133-143, 1991.

48. Juutilainen J, Laara E, Pukkala E. Incidence of leukemia and brain
tumours in Finnish workers exposed to ELF magnetic fields. Int Arch Occup
Environ Health 62, 289-293, 1990.

49. Kerbacher JJ, Meltz ML, Erwin DN. Influence of radiofrequency radiation
on chromosome aberrations in CHO cells and its interaction with DNA-damaging
agents. Radiat Res 123, 311-319, 1990.

50. Kirschvink JL, Kobayashi-Kirschvink A, Diaz-Rioci JC et al. Magnetite in
human tissue: a mechanisms for the biological effect of weak ELF magnetic
fields. Bioelectromagnetics, suppl 1, 101-113, 1992.

51. Lai H, Carino MA, Horita A et al. Opioid receptor subtypes that mediate
a microwave-induced decrease in central cholinergic activity in the rat.
Bioelectromagnetics 13, 237-246, 1992.

52. Lai H, Singh NP. Acute low-intensity microwave exposure increases DNA
single-strand breaks in rat brain cells. Bioelectromagnetics 16, 207-210,
1995.

53. Lâonard A, Berteaud AJ, BruySre A. An evaluation of the mutagenic,
carcinogenic and teratogenic potential of microwaves. Mutation Res. 123,
31-46, 1983.

54. Lester JR, Moore DF. Cancer mortality and air force bases. J
Bioelectricity 1, 77-82, 1982.

55. Liboff AR, Williams T Jr, Strong DM et al. Time-varying magnetic fields:
effect on DNA synthesis. Science 223, 818-820, 1984.

56. Lin R.S, Dischinger PC, Conde J et al. Occupational exposure to
electromagnetic fields and the occurence of brain tumours. J Occup Med. 27,
413-419, 1985.

57. London S, Thomas DC, Bowman JD et al. Exposure to residential electric
and magnetic fields and risk of childhood leukemia. Am J Epidemiol. 134,
923-937, 1991.

58. Loomis DP, Savitz DA, Ananth CV. Breast cancer mortality among female
electrical workers in the United States. J Natl Cancer Inst. 86, 921-925,
1994.

59. Lowenthal RM, Panton JB, Baikie MJ et al. Exposure to high-tension power
lines and childhood leukaemia: a pilot study. Med J Australia 155, 347,
1991.

60. Lyle DB, Schechter P, Adey WR et al. Supprression of T-lymphocyte
cytotoxicity following exposure to sinusoidally amplitude-modulated fields.
Bioelectromagnetics 4, 281-292, 1983.

61. Lyle DB, Ayotte RD, Sheppard AR et al. Suppression of T-lymphocyte
cytotoxicity following exposure to 60-Hz sinusoidal electric fields.
Bioelectromagnetics 9, 303-313, 1984.

62. Maes A, Verschaeve L, Arroyo A et al. In vitro cytogenetic effects of
2450 MHz waves on human peripheral blood lymphocytes. Bioelectromagnetics
14, 495-501, 1993.

63. Maes A, Collier M, Slaets D et al. Cytogenetic effects of microwaves
from mobile communication frequencies (954 MHz). Electro- Magnetobiol. 14,
91-98, 1995.

64. Maes A, Collier M, Slaets D et al. 954 MHz microwaves enhance the
mutagenic properties of mitomycin C. Environ Molec Mutagen., submitted,
1995.

65. Magin RL, Lu S-T, Michaelson SM. Stimulation of dog thyroid by local
application of high-intensity microwaves. Am J Physiol. 233, E363-E368,
1977.

66. Mancuso TF. Epidemiological study of tumours of the central nervous
system in Ohio. Ann NY Acad Sci. 381, 17-39, 1982.

67. Manikowska E, Luciani JM, Servantie B et al. Effects of 9.4 GHz
microwave exposure on meiosis in mice. Experientia 35, 388-389, 1979.

68. Manikowska-Czerska E, Czerski , Leach WM. Effects of 2.45 GHz microwaves
on meiotic chromosomes of male CBA/CAY mice. J Hered 76, 71-73, 1985.

69. Martens L, Verschaeve L, Maes A et al. Hinder: niet ioniserende
straling. Milieu- en Natuurrapport Vlaanderen, Leren om te keren,
Wetenschappelijk verslag, Vlaamse Milieumaatschappij, pp 43, 1994.

70. McDowell ME Mortality of persons resident in the vicinity of electricity
transmission facilities. Brit J Cancer 53, 271-279, 1986.

71. McLaughlin JK, Malker HSR, Blot WJ et al. Occupational risks for
intracranial gliomas in Sweden. J Natl Cancer Inst. 78, 253-257, 1987.

72. McLean JRN, Stuchly MA, Mitchell REJ et al. Cancer promotion in a
mouse-skin model by a 60-Hz magnetic field: II. tumor development and immune
response. Bioelectromagnetics 12, 273-288, 1991.

73. Meltz ML, Eagan P, Erwin DN. Proflavin and microwave radiation: absence
of a mutagenic interaction. Bioelectromagnetics 11, 149-157, 1990.

74. Milham S. Mortality in workers exposed to electromagnetic fields.
Environ Health Perspect. 62, 297-300, 1985.

75. Myers A, Clayden A, Cartwright RA et al. Childhood cancer and overhead
powerlines: a case-control study. Brit J Cancer 62, 1008-1014, 1990.

76. Olsen JH, Nielsen A, Schulgen G. Residence near high-voltage facilities
and the risk of cancer in children. Brit Med J. 307, 891-895, 1993.

77. Olsen JH. Etude âpidâmiologique sur l'apparition du cancer chez les
enfants exposâs a des lignes âlectriques É hautes tension. In: P Lannoye,
ed, La Pollution Electromagnâtique et la Santâ, Frison-Roche, Paris, pp
117-126, 1994.

78. Phelan AM, Lange DG, Kues HA et al. Modification of membrane fluidity in
melanin containing cells by low-level microwave radiation.
Bioelectromagnetics 13, 131-146, 1992.

79. Philips JL. Transferrin binding to two human colon carcinoma cell lines:
characterization and effect of 60-Hz electromagnetic fields. Cancer Res. 46,
239-244, 1986.

80. Polson P, Merritt JH. Cancer mortality and air force bases: a
reevaluation. J Bioelectricity 4, 121-127, 1985.

81. Preston-Martin S, Peters JM, Yu MC et al. Myelogenous leukemia and
electric blanket use. Bioelectromagnetics 9, 207-213, 1988.

82. Preston-Martin S, Mack W, Henderson BE. Risk factors for gliomas and
meningiomas in males in Los Angeles county. Cancer Res. 49, 6137-6143, 1989.

83. Reiter RJ, Anderson LE, Buschbom RL et al. Reduction of the nocturnal
rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in
utero and for 23 days after birth. Life Sci. 42, 2203-2206, 1988.

84. Reiter RJ, Dun-Xian T, Poeggeler B, et al. Melatonin as a free radical
scavenger: implications for aging and age-related diseases. Ann NY Acad Sci.
719, 1-12, 1994.

85. Robinette CD, Silverman, Jablon S. Effects upon health of occupational
exposure to microwave radiation (radar). Am J Epidemiol. 112, 39-53, 1980.

86. Rosenthal M, Obe G. Effects of 50-Hz eleectromagnetic fields on
proliferation and on chromosomal alterations in human peripheral lymphocytes
untreated or pretreated with chemical mutagens. Mutation Res. 210, 329-335,
1989.

87. Sahl JD, Kelsh MA, Greenland S. Cohort and nested case-control studies
of hematopoietic cancers and brain cancer among electric utility workers.
Epidemiology 4, 101-114, 1993.

88. Salford LG, Brun A, Persson BRR et al. Experimental studies of brain
tumour development during exposure to continuous and pulsed 915 MHz
radiofrequency radiation. Bioelectrochem Bioenerget. 30, 313-318, 1993.

89. Saunders RD, Kowalczuk CI, Beechey CV et al. Studies of the induction of
dominant lethals and translocations in male mice after chronic exposure to
microwave radiation. Int J Radiat Biol. 53, 983-992, 1988.

90. Saunders RD, Kowalczuk CI, Sienkiewicz ZJ. Biological effects of
exposure to non-ionizing electromagnetic fields and radiation. III.
Radiofrequency and microwave radiation. NRPB-R240, Chilton, Didcot,
Oxfordshire, UK, 1991.

91. Savitz DA, Wachtel H, Barnes FA et al. Case-control study of childhood
cancer and exposure to 60-Hz magnetic fields. Am J Epidemiol. 128, 21-38,
1988.

92. Savitz DA, Feingold L. Association of childhood cancer with residential
traffic density. Scan J Work Environ Health 15, 360-363, 1989.

93. Savitz DA, John EM, Kleckner RC. Magnetic field exposure from electric
appliances and childhood cancer. Am J Epidemiol. 131, 169-172, 1990.

94. Schreiber GH, Swaen GMH, Meijers JMM et al. Cancer mortality and
residence near electricity transmission equipment: a retrospective cohort
study. Int J Epidemiol. 22, 9-15, 1993.

95. Scott G. Free radicals provide a mechanism for EMF to promote cancer.
Electromagnet News 3, 6-8, 1992.

96. Severson RK, Stevens RG, Kaune WT et al. Acute nonlymphocytic leukemia
and residential exposure to power frequency magnetic fields. Am J Epidemiol.
128, 10-20, 1988.

97. Simunic D, ed. Proceedings of the COST 244 meeting on Electromagnetic
Hypersensitivity. European Union, DGXIII/72/95-EN, pp. 145, 1995.

98. Sinz R. Zeitstrukturen und organismische regulation. Academie Verlag,
Berlin, 1978.

99. Smith CW, Choi RYS, Monro JA The diagnosis and therapy of electrical
hypersensitivity. Clin Ecol. 6, 119-128, 1989.

100. Smith CW. Sensibilitâ chez les sujets allergiques. In: P Lannoye, ed,
La Pollution Electromagnâtique et la Santâ, Frison-Roche, Paris, pp 79-89,
1994.

101. Stevens RG Electric power use and breast cancer: a hypothesis. Am J
Epidemiol. 125, 556-561, 1987.

102. Stodolnik-Baranska W. Lymphoblastoid transformation of lymphocytes in
vitro after microwave irradiation. Nature 214, 102, 1967.

103. Szmigielski S, Szudzinski A, Pietraszek A et al. Accelerated
development of spontaneous and benzopyrene-induced skin cancer in mice
exposed to 2450-MHz microwave radiation. Bioelectromagnetics 3, 179-191,
1982.

104. Tarricone L, Cito C, D'Inzeo D. ACh receptor channel's interaction with
MW fields. Bioelectrochem Bioenerget. 30, 275-285, 1993.

105. Tenforde TS, Kaune WT. Interaction of extremely low frequency electric
and magnetic fields with humans. Health Phys. 53, 595-606, 1987.

106. Thâriault G. Health effects of electromagnetic radiation on workers:
epidemiologic studies. in: Proceedings of the Scientific Workshop on Health
Effects of Electromagnetic Radiation on Workers, NIOSH Pub US Department of
Health and Human Services, Cincinnati, OH, pp 91-124, 1991.

107. Thâriault G, Goldberg M, Miller AB et al. Cancer risks associated with
occupational exposure to magnetic fields among utility workers in Ontario
and Quebec, Canada, and France: 1970-1989. Am J Epidemiol. 139, 550-572,
1994.

108. Thomas TL, Stolley PD, Stemhagen A et al. Brain tumour mortality risk
among men with electrical and electronic jobs. J Natl Cancer Inst. 79,
233-237, 1987.

109. Tomenius L. 50-Hz electromagnetic environment and the incidence of
childhood tumors in Stockholm county. Bioelectromagnetics 7, 191-207, 1986.

110. Tornqvis S, Norell S, Ahlbom A et al. Cancer in electric power
industry. Brit J Ind Med. 43, 212-213, 1986.

111. Tornqvis S, Knave B, Ahlbom A et al. Incidence of leukaemia and brain
tumours in some 'electrical occupations'. Brit J Ind Med. 48, 597-603, 1991.

112. Tynes T, Andersen A, Langmark F. Incidence of cancer in Norwegian
workers potentially exposed to electromagnetic fields. Am J Epidemiol. 136,
81-88, 1992.

113. Vena JE, Graham S, Hellman R. Use of electric blankets and risk of
postmenopausal breast cancer. Am J Epidemiol. 134, 180-185, 1991.

114. Verreault R, Weiss NS, Hollenbach KA. Use of electric blankets and risk
of testicular cancer. Am J Epidemiol. 131, 759-762, 1990.

115. Verschaeve L, Slaets D, Van Gorp U et al. In vitro and in vivo genetic
effects of microwaves from mobile telephone frequencies in human and rat
peripheral blood lymphocytes. Proc COST-244 Meetings on Mobile
Communications and Extremely Low Frequency Fields and Instrumentation and
Measurements in Bioelectromagnetic Research, D. Simunic, ed, EEC,
DGXIII/131, 74-83, 1994.

116. Veyret B, Bouthet C, Deschaud P et al. Antibody response of mice
exposed to low-power microwaves under combined pulse-and amplitude
modulation. Bioelectromagnetics 12, 47-53, 1991.

117. Walborg EF. Extremely Low-Frequency Electromagnetic Fields and Cancer:
Focus on Tumor Initiation, Promotion, and Progression. National Electrical
Manufacturers Association, Washington, DC, 1991.

118. Warnke U. Bioinformation âlectromagnâtique: la sensibilitâ des ötres
humains et des animaux aux rayonnements non ionisants. In: P Lannoye, ed, La
Pollution Electromagnâtique et la Santâ, Frison-Roche, Paris, pp 63-78,
1994.

119. Weaver JC, Astumian RD. The response of living cells to very weak
electric fields: the thermal noise limit. Science 247, 459-461, 1990.

120. Wertheimer N and Leeper E. Electrical wiring configurations and
childhood cancer. Am J Epidemiol. 109, 273-284, 1979.

121. Wertheimer N and Leeper E. Adult cancer related to electrical wires
near the home. Int J Epidemiol. 11, 345-355, 1982.

122. WHO (1987) Environmental health criteria 69: magnetic fields. World
Health Organisation, Geneva, , 197 pp.

123. WHO (1993) Electromagnetic fields (300 Hz to 300 GHz), Environmental
Health Criteria nr 137, World Health Organisation, Geneva, 290 pp

124. Wilson BW, Anderson LE, Hilton DI et al. Chronic exposure to 60-Hz
electric fields: effects on pineal function in the rat. Bioelectromagnetics
2, 371-380, 1981.

125. Wilson BW, Chess EK, Anderson LE. 60-Hz electric field effects on
pineal melatonin rhythms: time-course for onset and recovery.
Bioelectromagnetics 7, 239-242, 1986.

126. Wilson BW, Stevens RG, Anderson LE. Neuroendocrine mediated effects of
electromagnetic field exposure: possible role of the pineal gland. Life Sci.
45, 1319-1332, 1989.

127. Youngson JHAM, Clayden AD, Myers A et al. A case-control study of adult
haematological malignancies in relation to overhead powerlines. Brit J
Cancer 63, 977-985, 1991.

Table I: Overview of some of the most representative epidemiological studies
on residential power-line cancer studies.
OR =odds ratio or relative risk, O/E=observed number of cases divided by the
expected number of cases, SMR=standardized mortality ratio (SMR=100 means no
increased or decreased risk), *=statistically significant.

Table 2: Overview of some of the most representative epidemiological studies
on the cancer incidence in workers who were professionally exposed to
ELF-fields.

Table 3: Effects of extremely low frequency and radiofrequency fields as
observed in in vitro and in vivo laboratory studies Compiled from
Gezondheidsraad (1992), EBC (1993), WHO (1993) and Martens et al. (1994).

Table 4: Domains where biological effects were ascribed to exposure to
extreme low frequency and radiofrequency electromagnetic fields (+). These
effects are not necessarily generally accepted.

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