CURRENT
STATE AND IMPLICATIONS OF RESEARCH ON BIOLOGICAL EFFECTS OF
MILLIMETER WAVES: A REVIEW OF LITERATURE
Andrei G.
Pakhomov, Yahya Akyel, Olga N. Pakhomova, Bruce E. Stuck, and
Michael R. Murphy
McKesson
BioServices (A.G.P., Y.A., O.N.P.), U. S. Army Medical Research
Detachment of the Walter Reed Army Institute of Research
(B.E.S.), and Directed Energy Bioeffects Division, Human
Effectiveness Directorate, Air Force Research Laboratory
(M.R.M.), Brooks Air Force Base, San Antonio, TX
Address for
correspondence:
Andrei G. Pakhomov
USA-MCMR, McKesson BioServices,
8308 Hawks Road, Building 1168,
Brooks Air Force Base, San Antonio, TX 78235-5324
PHONE (210)536-5599
FAX (210)536-5382
E-MAIL andrei.pakhomov@aloer.brooks.af.mil
Running title:
"Bioeffects
of Millimeter Waves"
ABSTRACT
In recent
years, research into biological and medical effects of
millimeter waves (MMW) has expanded greatly. The present paper
analyzes general trends in this area and briefly reviews most
significant publications, proceeding from cell-free systems,
dosimetry and spectroscopy issues, through cultured cells and
isolated organs to animals and humans. The studies reviewed
demonstrated effects of low-intensity MMW (10 mW/cm2 and less)
on cell growth and proliferation, activity of enzymes, state of
cell genetic apparatus, function of excitable membranes,
peripheral receptors, and other biological systems. In animals
and humans, local MMW exposure stimulated tissue repair and
regeneration, alleviated stress reactions, and facilitated
recovery in a wide range of diseases (MMW therapy). Many of
reported MMW effects could not be readily explained by
temperature changes during irradiation. This paper outlines some
problems and uncertainties in the MMW research area, identifies
tasks for future studies, and discusses possible implications
for development of exposure safety criteria and guidelines.
Key words:
Electromagnetic
fields, bioeffects, mm-wave band
INTRODUCTION
The term
"millimeter waves" (MMW) refers to extremely
high-frequency (30-300 GHz) electromagnetic oscillations.
Coherent oscillations of this range are virtually absent from
the natural electromagnetic environment, which might have had
important consequences. First, living organisms could not have
developed adaptation to MMW during the course of evolution on
Earth. Second, some specific features of MMW radiation and the
absence of external "noise" might have made this band
convenient for communications within and between living cells
[Golant, 1989; Betzky, 1992]. These arguments, though not
adequately proven, are often used to explain high MMW
sensitivity of biological subjects. Indeed, MMW have been
reported to produce a variety of bioeffects, many of which are
quite unexpected from a radiation penetrating less than 1 mm
into biological tissues. A number of theoretical models have
been set forth to explain peculiarities and primary mechanisms
of MMW biological action [Fröhlich 1980, 1988 (ed); Golant,
1989; Grundler and Kaiser, 1992; Belyaev et al., 1993a; Kaiser,
1995].
One of the most
remarkable events in contemporary electromagnetic biology is a
surge in interest in MMW biological and medical effects in the
countries of the former Soviet Union (FSU). A striking
difference in the FSU and "non-FSU" research activity
in this area can be seen from counts of related publications.
For example, the EMF Database1 v. 3.0 (1997) lists a
total of 463 FSU publications on MMW-related topics, and only
261 such publications from the rest of the world. Though these
numbers should not be taken as exact (the Database includes
most, but certainly not all relevant citations), the situation
in general is portrayed correctly and is particularly explicit
in a historic perspective (Fig. 1). The non-FSU production
reached its peak of 52 papers (including meeting abstracts) in
1983-1984, which was 3.3% of all non-FSU publications in the
bioelectromagnetics area; then it gradually declined to only
seven papers (0.5%) in 1989-1990. Concurrently, MMW research in
the FSU expanded greatly: Both the count of publications (up to
120 in 1995-1996) and their portion in the FSU
bioelectromagnetic research (20 to 30%) far exceeded these
numbers for non-FSU publications.
Aside from the
number of studies, there are important qualitative differences.
Western (non-FSU) research was largely driven by concerns for
public safety. However, safety issues occupy a relatively small
portion of the FSU research, while far more studies are related
to medical applications of MMW. Over 50 diseases and conditions
have been claimed to be successfully treated with MMW alone or
in combination with other means. Lebedeva and Betskii [1995]
have reported more than a thousand MMW therapy centers in the
FSU and over 3 million people received this therapy. Naturally,
the extensive medical use of MMW has stimulated basic research
as well.
Nowadays, MMW
technologies are increasingly being employed in practical
applications (e.g., wireless communication, traffic and military
radar systems), making it imperative that bioeffects data be
available for health hazard evaluation and restoring the
interest to MMW biological research in the West. The number of
non-FSU publications on this topic is again increasing, a
specialized MMW session appeared at the 1996 and 1997 meetings
of the Bioelectromagnetics Society, and the first Infrared
Lasers and MMW Workshop was held at Brooks AFB, TX in 1997.
Unfortunately, the FSU research, a rich source of MMW bioeffects
data, is not readily available in the West and is scarcely known
by Western scientists.
The present
paper is intended to fill in this gap by looking over recent
research in the MMW field, from molecules and cells to MMW
therapy. We have analyzed over 300 original FSU publications and
about 50 non-FSU papers, and selected those which appeared more
interesting and credible. This review is primarily focused on
experimental and clinical findings reported during the last
decade; therefore, it includes only a few essential citations of
earlier publications and does not cover such topics as
theoretical modeling of possible interaction mechanisms.
Interested readers should see other reviews for additional
information [Fröchlich, 1980; 1988 (ed.); Gandhi, 1983;
Grundler, 1983; Postow and Swicord, 1986; Belyaev, 1992].
1.
PHYSICO-CHEMICAL EFFECTS, MMW ABSORPTION AND SPECTROSCOPY
A number of
independent studies have shown specific MMW effects in the
absence of living subjects, i.e., in solutions of biomolecules
and even in pure water.
Fesenko and
Gluvstein [1995] analyzed MMW effects on periodic voltage
oscillations during a discharge of a water capacitor. The
capacitor, which was a distilled water sample in a 1-mm
capillary, was charged by 18 V, 1-ms wide unipolar rectangular
pulses. The capacitor discharged within 500-600 ms after a
pulse. The discharge curve contained periodic voltage
oscillations reaching 10-15 mV. Fourier spectrum of these
oscillations consisted of two strong peaks, at 5.25 and 46.8 Hz,
and these peaks did not change during at least two hours of
experimentation. The water sample was exposed at 36 GHz from an
open-ended waveguide (7.2 x 3.4 mm cross-section). Irradiation
at 50 m W output power greatly reduced the 46.8 Hz peak in 1 min
and virtually eliminated it in 10 min, and also shifted the 5.25
Hz peak to 6.75 Hz. These changes showed little or no recovery
within 20-60 min after cessation of a 10-min exposure.
Irradiation at 5 mW output power produced similar changes, but,
unexpectedly, was far less effective: the changes developed more
slowly, and the original peaks restored more quickly. Mechanisms
of the phenomenon itself, its anomalous power sensitivity, and
the long-lasting "memory" of water were not
understood. The authors suggested that MMW-induced changes in
water properties could underlie biological effects.
Direct MMW
effects on pure water properties were also observed by
holographic interferometry [Berezhinskii et al., 1993; Litvinov
et al., 1994]. Refraction of light in fluid was determined from
the width and number of interference bands formed by a He-Ne
laser beam (630 nm) passing through the fluid and a referent
beam. Irradiation of distilled water at 10 mW output power for
5-7 min caused no effect at 41.5 GHz, but decreased the number
of the interference bands from 6 to 5 at 51.5 GHz; the distance
between the bands increased 1.2 times. These changes developed
faster and were more profound in a 2% human blood plasma
solution. The effect reached saturation in 6-7 min and was
completely reversible. Both theoretical calculations and direct
measurements established that maximum MMW heating was about 1 oC.
MMW-induced changes in the light refraction coefficient were
almost an order of magnitude greater than produced by 1 oC
conventional heating, and therefore were attributed to a
specific effect of MMW.
Other
properties of blood plasma, such as dielectric permittivity and
absorption coefficient, could be altered by MMW irradiation as
well [Belyakov et al., 1989]. Changes in these parameters
measured only 0.05-0.5%, but were well beyond the accuracy of
the method used (0.01%). The sensitivity of plasma samples to
particular radiation wavelengths strongly varied from one blood
donor to another.
Khizhnyak and
Ziskin [1996] analyzed peculiarities of MMW heating and
convection phenomena in water solutions. Besides the most
expected reaction (gradual temperature rise), irradiation could
induce either temperature oscillations and a decrease in average
temperature, or a biphasic response in which the temperature
initially rises and then decreases. These anomalous effects
resulted from convective processes, i.e., the formation of a
toroidal vortex. When the vortex became stable, the temperature
decreased following the initial rise phase, although the
irradiation was constantly maintained. The local temperature
could decrease with increasing power density, and in biological
systems this would appear as an effect opposite to heating.
Probably, this phenomena could explain some of reported
"nonthermal" MMW effects. If irradiation continued for
a long time (30-40 min), the convection phenomena disappeared
and could not be reintroduced even after restoration of the
initial temperature. This observation suggested that some
irreversible process had occurred in the liquid, which resembles
findings of the water "memory" cited above.
The supposed
role of water as a primary target for MMW radiation motivated
Zavizion et al. [1994] and Kudryashova et al. [1995] to study
how MMW absorption at the wavelengths of 2.0, 5.84, and 7.12 mm
is affected by the presence of other substances, namely a -amino
acids (0.25-2.5 mol/l). Since MMW absorption by amino acid
molecules is negligible, the absorption of solutions, in most
cases, decreased proportionally to the amino acid concentration.
This difference in absorption by pure water and solutions, or
"absorption deficit", increased with increasing the
length of the hydrophobic radical in a series of homologous
amino acids (glycine -alanine -GABA -valine). Paradoxically, the
absorption deficit was negative for sarcosine at 5.84 mm and
7.12 mm, and for glycine at all the wavelengths, meaning that
these two amino acids can increase MMW absorption by water
molecules.
A detailed
theoretical analysis of MMW absorption in flat structures with
high water content was performed by Ryakovskaya and Shtemler
[1983]. The authors produced dependencies of the specific
absorption rate (SAR) on the radiation frequency, temperature,
thickness of the absorptive medium, and presence of dielectric
layer(s) above and/or underneath. This work modeled most common
biological setups, such as irradiation of cell suspensions in
Petri dishes, cuvettes, etc. The wavelength in the medium,
reflection coefficients, depth of penetration, and SAR at the
surface of a semi-infinite absorptive medium were calculated for
wavelengths from 1 to 10 mm, with 1-mm steps. For example, the
depth of penetration for 1- and 10-mm wavelengths at 20 oC
equals 0.195 mm and 0.56 mm, respectively, and the surface SAR
reaches 79.4 and 15.5 mW/cm3 per 1 mW/cm2. Exposure through a
thin dielectric layer (e.g., bottom of a Petri dish) may
decrease reflection and further increase SAR by up to 2.5 times.
SAR in thin absorptive films (0.1-0.01 mm) increases greatly and
may exceed SAR at the surface of a semi-infinite medium more
than tenfold. Furthermore, presence of a dielectric above or
below the thin absorptive film may increase SAR in it as much as
20-fold. Apparently, the possibility of reaching very high SAR
levels and of local heating cannot be underestimated even for
the incident power levels that are often regarded as nonthermal
(0.1-1 mW/cm2).
2. MMW EFFECTS
AT SUBCELLULAR, CELLULAR, AND TISSUE LEVELS
2.1 Growth rate
effects
Debates about
resonance growth rate effects of MMW have been going on for over
20 years, and this problem was widely discussed in earlier
reviews. In brief, Grundler and co-authors [1977, 1982, 1988]
reported that the yeast Saccharomyces cerevisiae growth
rate may be either increased by up to 15%, or decreased by up to
29%, by certain frequencies of MMW within a 41.8-42.0 GHz band.
The effect was established by different methods, both in
suspended cells and in monolayer. According to recent
observations [Grundler and Kaiser, 1992], an effect of about the
same magnitude is produced by the field intensities from 5
pW/cm2 to 10 mW/cm2 (8 kHz modulation). The width of the
resonance peaks increased with the intensity from about 5 MHz to
12-15 MHz for the above intensity range. However, thorough
independent attempts to replicate these findings were not
successful [Furia et al., 1986; Gos et al., 1997], suggesting
that these MMW effects could be dependent on (or even produced
by) some yet unidentified and uncontrolled conditions.
Dardanoni and
co-authors [1985] observed frequency-and modulation-dependent
effects on the growth of yeast Candida albicans. MMW
modulated at 1 kHz reduced the growth rate by about 15% at 72
GHz, but not at 71.8 or 72.2 GHz. A 3-hour continuous wave (CW)
irradiation at 72 GHz had the opposite effect, i. e., increased
the growth rate by about 25% over the sham irradiated control.
Remarkable variability of the results was noted, which could be
a result of cell subpopulations with different sensitivity.
Golant and
co-authors [1994] reported that a marked synchronicity of
periodic fluctuations in the growth rate and bud formation in
the culture of S. cerevisiae can be induced by 0.03
mW/cm2, 46 GHz irradiation for 50 min. This effect was claimed
to persist for over 20 cell generations. Periodicity of bud
formation was observed in control samples as well, but it was
less pronounced and had a different time duration (60 min versus
80 min after MMW exposure).
Synchronizing
effects of MMW were also observed in higher plant specimens
(Shestopalova et al., 1995). Barley seeds were exposed for 20
min at 0.1 mW/cm2 (61.5 GHz), then the exposed and control seeds
(150 seeds per group) were put into an incubator for sprouting.
The incubator was maintained at either 28 oC or 8 oC.
Cytological examination established that the degree of
synchronization of cell division in MMW-exposed sprouts
increased by 36% (28 oC) and 50% (8 oC)
over the respective controls.
Levina et al.
[1989] studied MMW effects on the development of a Protozoan Spirostum
sp. cell population. The population began in a saline medium
with beer yeast (550 mg/l) as food by adding of 5-6 protozoan
cells/ml. The culture was exposed for 30 min at 1.5 mW/cm2
(7.1-mm wavelength), a single time between days 2 and 11 of the
growth. Unexposed cultures grew exponentially up to a density of
100 cells/ml on day 11, then rapidly died without reaching
stationary phase, obviously due to poisoning by waste products.
Exposures performed on days 2, 4, or 7 caused the populations to
enter the stationary phase on or around day 9. Exposures
performed on day 9 or 11 postponed the population death by 5
days, and the final cell content increased to 115-135 cells/ml
on day 14. Irradiation on day 2 also increased the proliferation
rate, and by day 7 the cell density was nearly twice as high as
in control samples. In another series of experiments, the
population began with the initial concentration of 1-2 protozoan
cells/ml, and stabilized in 8-10 days at 12-13 cells/ml. In
these cultures, MMW exposure suppressed proliferation, and the
final cell density was only 6-10 cells/ml. This study indicated
that irradiation affects the population's own growth control
mechanisms, and that the effect depends on the stage and other
particulars of the population development.
Exposure for 30
min at 2.2 mW/cm2, 7.1-mm wavelength enhanced the growth of a
blue-green algae Spirulina platensis by 50% [Tambiev et
al., 1989], while 8.34-mm wavelength produced no changes
compared with sham control. The alga growth rate more than
doubled when a 30-min irradiation at 7.1-mm was immediately
followed by exposure to high-peak power microwave pulses (15
pulses, 10-ns pulse width, 6-min pause, 3-cm wavelength,
200-kW/cm2 peak incident power density). Concurrently,
photosynthetic oxygen evolution increased about 1.5 times. The
observed stimulatory effects are of considerable promise in
biotechnology, where S. platensis is used for production
of food protein and biologically active compounds.
Other
publications by the same authors [Tambiev and Kirikova, 1992]
and independent investigators [Rebrova, 1992; Shub et al., 1995]
declared observed MMW effects on the growth rate of several
species of bacteria, cyanobacteria, algae, yeasts, and higher
plants (fennel, lettuce, tomato). For example, in yeasts S.
cerevisiae and S. carlsbergensis MMW shortened the
phases of culture growth 2.3-6.0 times, and could increase the
biomass production rate to 253%. Effects on Escherichia coli
growth could be either stimulatory or inhibitory, depending on
the wavelength (6.0-6.7 mm band, £ 1 mW/cm2 for 30 min).
However, all three papers were written as summaries of the
authors' multiyear experiences with studying these and other MMW
effects, and did not provide enough detail for full evaluation
or possible replication.
2.2. Chromosome
alterations and genetic effects of MMW.
Absence of
mutagenic or recombinagenic effects of MMW radiation was clearly
demonstrated in the late 1970's [Dardalhon et al., 1979, 1981],
and later investigations were consistent with this conclusion.
At the same time, a number of studies indicated that MMW could
affect the fine chromosome structure and function, cell
tolerance to standard mutagens and lesion repairs.
Best known is
the recent work by Belyaev and co-authors [1993a, b, 1994,
1996], who discovered sharp frequency resonances by using an
anomalous viscosity time dependence (AVTD) technique. This
technique is supposed to reflect fine changes in DNA
conformation and DNA-protein bonds. At a resonance frequency,
biological changes could be produced by field intensities as low
as 10-19 W/cm2. The magnitude of changes gradually increased
with the field intensity and reached a plateau between 10-17 and
10-8 W/cm2, depending on cell density in exposed samples.
Resonance peaks for E. coli cells were found at 51.76 and
41.34 GHz; these values decreased in strains with increased
haploid genome length. These results pointed to the chromosomal
DNA as a target for resonance interaction between living cells
and MMW. The width of the resonances increased from units to
tens of MHz by increasing the incident power, and this
dependence is in a notable agreement with the one reported for
cell growth rate effects [Grundler and Kaiser, 1992].
However, the
AVTD test is not a conventional technique in cell biology.
Interpretation of AVTD data is uncertain and functional
consequences of AVTD changes have not yet been convincingly
defined. A discussion is going on as to whether super-low
radiation intensities in these studies were measured correctly
[Osepchuk and Petersen, 1997; see also their letter and
Belyaev's reply in one of forthcoming BEM issues]. Supposedly,
some power at a harmonic frequency might be transmitted to the
sample despite large attenuation at the fundamental frequency.
Whether this was the case or not, consistent observations of
resonance effects represent an important finding, which requires
understanding and independent replication.
MMW induced
visible changes in giant chromosomes of salivary glands of the
midge Acricotopus lucidus [Kremer et al., 1988]. A
certain puff, the Balbiani ring BR1 in the chromosome II reduced
in size after irradiation at 67,200± 0.1 MHz or 68,200± 0.1
MHz (<5 mW/cm2), and this effect appeared to be unrelated to
heating. Numerous alterations in the giant chromosome morphology
were also independently found in Chironomus plumosus (Diptera)
after a 15-min exposure at 1 mW/cm2 [Brill' et al., 1993].
Exposure of
UV-treated E. coli culture to MMW at 61± 2.1 GHz, 1
mW/cm2 increased cell survival [Rojavin and Ziskin, 1995]. The
most likely mechanism of this effect was either direct or
indirect activation of the dark repair system. No survival
effects were found if the sequence of exposures was reversed, i.
e., when UV irradiation was performed immediately after a 10- to
30-min MMW exposure.
Genetic effects
of 61.02-61.42 GHz radiations were studied in D7 strain of the
yeast S. cerevisiae [Pakhomova et al., 1997]. MMW
exposures lasted for 30 min at 0.13 mW/cm2, and were followed in
60 min by a 100 J/m2 dose of 254 nm UV radiation. Compared with
the parallel control, the MMW pretreatment did not affect cell
survival or the rate of reverse mutations, but significantly
increased the incidence of gene conversions. Sham-exposed
samples showed no differences from respective parallel controls.
The data suggested that MMW did not alter the UV-induced
mutagenesis, but might facilitate UV-induced recombinagenic
processes. Thermal mechanism of this effect was improbable,
although could not be ruled out entirely.
2.3 Excitable
tissues and membranes
Along with the
genetic apparatus, the cell membrane is another site suspected
to be a primary target for MMW radiation. Many of the works
discussed below established profound MMW effects; however, only
a few attempts have been made to replicate them.
Brovkovich et
al. [1991] reported that 61 GHz, 4 mW/cm2 radiation
significantly activates the Ca++ pump in the
sarcoplasmic reticulum (SR) of skeletal and heart muscles of the
rat. The rate of Ca++ uptake by SR membranes was
measured by an ion-selective electrode in an ATP-containing
medium. An intermittent MMW treatment (5 min exposure, 15 min
pause, 3 cycles) of skeletal muscle SR increased the rate of
Ca++ uptake by 23%, and this increased level has retained for
one hour after the exposure. Uninterrupted MMW irradiation had
no effect in 10 min, but increased Ca++ uptake by 27%
in 20 min, and the effect reached maximum (48%) in 40 min. In
heart muscle SR, even a 5-min exposure enhanced Ca++
uptake by 18%.
Geletyuk and
co-authors [1995] used patch-clamp (inside-out mode) to study
42.25 GHz radiation effects on single Ca++-activated
K+ channels in cultured kidney cells (Vero). Exposure
for 20-30 min at 0.1 mW/cm2, CW, greatly modified the activation
characteristics of the channels, in particular, the open state
probability. The field increased the activity of channels with a
low initial activity, and inhibited channels with initially high
activity. In a subsequent study [Fesenko et al., 1995], these
effects were reproduced without direct irradiation of the
membrane, just by applying bathing solution pre-exposed for 30
min at 2 mW/cm2, 42.25 GHz. Irradiation of the solution did not
alter its pH or Ca++ concentration, and the nature of
the MMW-introduced channel-modifying properties of the solution
is not understood. The solution retained its biological efficacy
for at least 10-20 min after cessation of the exposure.
Kataev and
co-authors [1993] used voltage clamp to study membrane currents
in giant alga cells (Nitellopsis obtusa, Characea).
Irradiation for 30-60 min at 41 GHz, 5 mW/cm2 suppressed the
chloride current to zero with no recovery for 10-14 hours.
Marked inhibitory effects were also found at 50 and 71 GHz,
while most of other tested frequencies in 38-78 GHz range
enhanced the chloride current up to 200-400% (49, 70, 76 GHz).
This activation was reversible, and recovery to the initial
value took 30-40 min. Moreover, "activating"
frequencies could restore the chloride current after its
complete and normally irreversible suppression by
"inhibitory" frequencies. MMW heating did not exceed 1
oC, and neither activating nor inhibitory effects
were related to, or could be explained by it. Calcium current
also changed during irradiation, but this effect was not
frequency-dependent and could be adequately explained by
heating. The authors noted that algae collected in the fall of
1990 and stored over the winter have entirely lost MMW
sensitivity by February 1991.
Experiments
with artificial bilayer membranes and snail neurons did not
reveal any frequency-specific effects of MMW [Alekseev and
Ziskin, 1995; Alekseev et al., 1997]. The capacitance of
artificial membranes, ionic channel currents, and the transport
of tetraphenylboron anions changed proportionally to MMW
heating, regardless of the frequency (53-78 GHz range) or
modulation employed. Irradiation of snail neurons at 75 GHz (600
to 4,200 W/kg) produced biphasic alterations of their firing
rate, which were similar to those caused by equivalent
conventional heating.
Burachas and
Mascoliunas [1989] studied MMW effects on the compound action
potential (CAP) in isolated frog sciatic nerve.. CAP decreased
exponentially and fell tenfold within 50-110 min of exposure at
77.7 GHz, 10 mW/cm2. CAP restored entirely soon after the
exposure, but the nerve became far more sensitive to MMW: CAP
suppression due to the next exposures became increasingly steep
and finally took only 10-15 min. This sensitized state persisted
for at least 16 hours. In addition to this "slow"
response, switching the field on increased CAP amplitude
instantly by 5-7%, and switching it off caused the opposite
reaction. These effects were found in "winter" frogs,
but weakened and finally disappeared in spring.
A different
effect in the isolated frog nerve was described by Chernyakov
and co-authors [1989]. The exposures lasted for 2-3 hours,
either with a regular frequency change by 1 GHz every 8-9 min,
or with a random frequency change every 1-4 min (53-78 GHz band,
0.1-0.2 mW/cm2). The latter regimen induced an abrupt CAP
"rearrangement" in 11 out of 12 exposed preparations:
the position, magnitude, and polarity of CAP peaks (the initial
CAP was polyphasic) drastically changed in an unforeseeable
manner. The other exposure regimen altered the amplitude and
duration of late CAP components in 30-40 min. The authors
supposed that MMW increased CAP conduction velocity in fast
nerve fibers and decreased it in slow fibers.
Neither of
these effects on CAP conduction was observed by Pakhomov et al.
[1997a]. Irradiation for 10-60 min either at various constant
frequencies, or with a stepwise frequency change did not alter
CAP at 0.2-1 mW/cm2. At 2.0-2.8 mW/cm2, it produced minor
changes, which were independent from the frequency and matched
the effect of heating. At the same time, a different MMW effect
was revealed using a high-rate nerve stimulation test. MMW
attenuated the stimulation-induced CAP decrease in a
frequency-dependent manner. The effect reached maximum at 41.34
GHz [Pakhomov, 1997b], and at this frequency the magnitude of
changes was the same (20-25%) at 0.02, 0.1, and 2.6 mW/cm2
[Pakhomov et al., 1997c]. A 100-MHz deviation from 41.34 GHz (to
41.24 or 41.44 GHz) reduced the effect about twofold, and a
200-MHz deviation eliminated it. The field distribution over the
preparation at these frequencies was virtually the same, so
different MMW absorption or heating patterns could not account
for the frequency-specificity of the effect. Interestingly, the
most effective frequency in these experiments happened to be the
same as the resonance frequency in the cell genome studies of
Belyaev et al. [1993a].
Low-intensity
MMW radiation effectively changed membrane functions in striated
muscle and cardiac pacemaker cells [Chernyakov et al., 1989].
Exposure at 0.1-0.15 mW/cm2 for 90 s or less (frequencies
between 54 and 78 GHz) decelerated the natural loss of
transmembrane potential in myocytes, or even increased it by
5-20 mV. Exposure reduced the overshoot voltage, action
potential amplitude and conduction velocity. This effect was
observed in 80% of exposures, with no clear dependence on the
radiation frequency. MMW influence on pacemaker activity was
analyzed in 990 experiments with 80 tissue strip preparations
from the frog heart sinoatrial area. In most cases, irradiation
immediately (often in less than 2 s) decreased the interspike
interval. The maximum effect was reached within 30 s. The
changes linearly increased with the incident power increase in
the range from 20-30 to 500 m W/cm2. The frequency dependence of
the effect was individual, with at least four maximums in the
studied range. Maximum preparation heating after a 2-s exposure
at 1 mW/cm2 was calculated as 0.005 oC. With a
physiological response latency of less than 2 s, this response
could not be thermal. Exposure to infrared light (4- to 6-m m
wavelength) often evoked the same effects as MMW, but the
threshold intensity was hundreds times greater.
In other
experiments described in the same paper, low-intensity MMW
synchronized firing of urinary bladder mechanoreceptors;
suppressed and altered the T-peak of EKG of in situ
exposed myocardium; enhanced respiration, altered membrane
calcium binding, and reduced the contractility of
cardiomyocytes. Summarizing their results, the authors stated
that the dependence of bioeffects upon radiation frequency is
not monotonic. Peaks of this dependence are individual and are
not fixed at particular frequencies, and they become smoother
with increased complexity of physiological control mechanisms
involved.
2.5 Other in
vitro effects
Bulgakova et
al. [1996] studied how MMW exposure of S. aureus affects
its sensitivity to antibiotics with different mechanisms of
action. Irradiations lasted from 1.5 to 60 min (54 or 42.195
GHz, or 66-78 GHz band with 1 GHz steps, ³ 10 mW/cm2). MMW
heating did not exceed 1.5 oC. Over 1,000 experiments
with 14 antibiotics were completed. A difference in the growth
of exposed cells compared to controls was most often observed
with polypeptide antibiotics, which affect the cell membrane
(gramicidin group), but not with inhibitors of cell wall
synthesis (penicillin group), of DNA-dependent RNA synthesis
(actinomycin D), of the RNA polymerase and RNA synthesis
(heliomycin), or protein biosynthesis inhibitors (neomycin,
tetracycline, etc.). Irradiation either increased or decreased
the antibiotic sensitivity, and the probability of these
opposite effects depended on the antibiotic concentration. MMW
could induce sensitivity to sub-bactericidal antibiotic
concentrations, which normally would not affect the cell growth.
Within studied limits, the effect showed no clear dependence on
the radiation intensity or frequency. The data suggested that
some membrane processes might be a target for the MMW effect.
The authors also noted that MMW treatment can reveal (or even
induce) the heterogeneity of the sensitivity of a cell
population to certain antibiotics.
Rebrova [1992]
reviewed various MMW effects on cell metabolism, synthesis of
enzymes, and other processes in unicellular organisms, e.g.,
frequency-dependent enhancement and suppression of colicin
synthesis in E. coli, stimulation of synthesis of
fibrinolytic enzymes in Bacillus firmus, increasing of
the contents of peptides, DNA, and RNA in B. mucilaginous,
and suppression of tolerance to antibiotics in Staphylococcus
aureus. The maximum magnitude of MMW-induced changes ranged
from 20 to 90%, depending on the wavelength and the initial
condition of the strain. In contrast to bacteria, reproduction
rate and biosynthetic properties of fungi Aspergillus sp.,
Endomyces fibuliger, and Dacthilyum dendraides
changed only after repeated exposures (10 times). Certain MMW
frequencies increased alpha amylase activity in A. orizae
by 67% and suppressed glucoamylase by 30%; others had the
opposite effect. In yeast species, MMW accelerated
maltose fermentation by 73%, while synthesis of diacetil and
aldehydes decreased by 20%. New biosynthetic culture properties
introduced by exposure persisted in at least 100 (S.
carlsbergensis) and 300 (S. cerevisiae) cell
generations. The selective stimulation of production of some
enzymes and suppression of others is promising for
biotechnology.
An unusual
"double-resonance" effect of MMW was described by
Gapeev et al. [1994]. Spontaneous locomotor activity of the
Protozoan Paramecium caudatum was not affected by
irradiation unless both the radiation frequency and modulation
were tuned to "resonance" values. These values were
42.25 GHz and 0.0956 Hz, respectively (0.5 duty ratio). At these
parameters, the threshold field intensity was about 0.02 mW/cm2.
The effect reached maximum (about 20%) at 0.1 mW/cm2, and
remained at this level at intensities up to 50 mW/cm2, despite
increasing heat production (0.1-0.2 oC at 5 mW/cm2).
CW irradiation or modulation rates of 16, 8, 1, 0.5, 0.25, or
0.05 Hz produced no effect, regardless of the field intensity or
heating. At the resonance modulation frequency, a shift of the
carrying frequency to 42.0 or 42.5 GHz eliminated the reaction.
No effects were observed with heating of samples by other means,
e.g., infrared light modulated at 0.0956 Hz. Locomotor activity
changes similar to the MMW effect could be evoked by increasing
the level of intracellular calcium, pointing to a possible
mechanism of the MMW action. However, reasons for the
"double-resonance" dependence of this MMW effect
remain unclear.
More reported
MMW effects in various in vitro systems are summarized in
Table 1.
3. ANIMAL AND
HUMAN STUDIES
3.1. MMW
effects on peripheral receptors
Abundant
evidence for MMW effects in directly exposed specimens neither
explains nor predicts possible effects at the organism level. It
is clearly understood that MMW penetration into biological
tissues is rather shallow, and any primary response must occur
in skin or subcutaneous structures, or at the eye surface. This
primary response would then mediate all subsequent reactions via
neural and/or humoral pathways. The nature of the primary
response and consequent events has been a subject of intense
speculation [Golant, 1989; Mikhno and Novikov, 1992; Rodshtadt,
1993], but there is little experimental proof. As a matter of
fact, the link between cellular and organism effects is missing
and remains the least understood area in the MMW field. However,
several studies have suggested that peripheral receptors and
afferent nerve signaling could be involved in the whole
organism's response to a local MMW exposure.
Akoev et al.
[1992] studied the response of electroreceptor Lorencini
capsules in anesthetized rays. Spontaneous firing in the
afferent nerve fiber from the capsule could be either enhanced
or inhibited by MMW irradiation (33-55 GHz, CW). The most
sensitive receptors increased their firing rate at intensities
of 1-4 mW/cm2, which produced less than 0.1 oC
temperature rise. Intensities of 10 mW/cm2 and higher could
evoke a delayed inhibition of firing, so the response became
biphasic. The authors emphasized that what they observed was not
merely a bioeffect of MMW, but was indeed a specific response of
the receptor.
Chernyakov and
co-authors [1989] were able to induce heart rate changes in
anesthetized frogs by MMW irradiation of remote skin areas. The
latency of the changes was about 1 min. Complete denervation of
the heart did not prevent the reaction, but decreased its
probability. The data suggested a reflex mechanism of the MMW
action, maybe involving certain peripheral receptors.
These data are
in agreement with later findings by Potekhina et al. [1992].
Certain frequencies from 53-78 GHz band (CW) effectively changed
the natural heart rate variability in anesthetized rats. The
radiation was applied to the upper thoracic vertebrae for 20 min
at 10 mW/cm2 or less. The frequencies of 55 and 73 GHz caused
pronounced arrhythmia: the variation coefficient of the R-R
interval increased 4-5 times. Exposure at 61 or 75 GHz had no
effect, and other tested frequencies caused intermediate
changes. Skin and whole-body temperature of the animals remained
unchanged. Similar frequency dependence was observed in
additional experiments with 3-hour exposures; however, about 25%
of experiments were interrupted because of sudden animal death
that occurred after 2.5 hours of exposure at 51, 61, and 73 GHz.
Possible role of receptor structures and neural pathways in the
development of the MMW-induced arrhythmia was discussed.
Sazonov et al.
[1995] compared alterations of spontaneous afferent firing in
bladder nerve in frogs when the bladder was exposed to infrared
radiation and to MMW (42.19 ± 0.15 GHz, 10 mW/cm2). The
infrared intensity was adjusted to produce the same heating as
MMW. In control experiments, the firing rate was stable for at
least 1-1.5 hours, but MMW increased it instantly from 30.9 to
32 spikes/s (p<0.05), and to 48.3 spikes/s (p<0.01) by the
end of a 20-min exposure. Immediately after cessation of
irradiation, the rate fell to 35.8 spikes/s, which was still
significantly higher (p<0.05) than before the treatment.
Infrared irradiation did not cause statistically significant
changes. This difference was interpreted as a proof of a
specific (nonthermal) MMW effect, which, in principle, might
take place in skin receptors as well.
In contrast,
infrared light and MMW at equivalent intensities produced
similar effects on the firing rate of crayfish stretch receptor
[Khramov et al., 1991]. Changes were proportional to the average
incident power, regardless of modulation or radiation frequency,
and were regarded as merely thermal.
The possibility
of modifying the peripheral receptor function by low-intensity
MMW has been demonstrated directly by Enin and co-authors
[1992]. An electrodynamic mechanostimulator was used to apply
mechanical stimuli (50 ms duration, 1-2 mm amplitude) to
individual skin mechanoreceptors on the sole of the hind limb of
anesthetized rats. Responses to the stimuli were recorded from
afferent fibers in the isolated and cut peripheral end of the
tibial nerve. The sole was exposed to 55-, 61-, or 73-GHz
radiation at 0.75, 2.90, or 7.81 mW/cm2, respectively. Exposure
lasted for 35 min and caused no changes in the skin temperature
(0.01 oC accuracy). MMW did not excite
mechanoreceptors, but markedly altered the threshold and latency
of their response to mechanic stimuli. In some receptors, the
threshold gradually increased, up to 180% of the initial value.
In others, the threshold initially decreased by 8-12%, recovered
within 10 min, and increased to 160% by the 25th min of
irradiation; after that, the receptors became completely
inactive and no longer responded to mechanical stimuli. The
receptor response latency under exposure could fall to 70%, or
rise to 120%, or the changes were biphasic. The MMW-induced
changes were maximum at 73 GHz, intermediate at 55 GHz, and
minimum at 61 GHz, despite the fact that the incident power at
61 GHz was 4-fold greater than at 55 GHz. The authors supposed
that sensations reported by patients under MMW therapy
(vibration, warmth, numbness, etc.) may result from functional
disturbances and blockage of receptors.
The ability of
humans to detect weak MMW has also been repeatedly established
under double-blind conditions [Lebedeva, 1993, 1995;
Kotrovskaia, 1994]. An examinee was situated in an isolated room
and had no contact with the experimenter. The outer surface of
the hand was exposed 20 times, for 1 min each. Exposures were
separated by 1-min intervals and randomized with sham exposures.
The start and end of each irradiation and placebo were
accompanied by sound clicks. The examinee had to push a button
when he felt the field. Neither examinee nor researcher knew the
sequence of exposures and sham exposures; correct and incorrect
reactions were recorded automatically. Field perception was
characterized by the reaction reliability (the percent of MMW
exposures detected) and the false alarms level (the percent of
sham exposures erroneously detected). An examinee was regarded
as capable of detecting the field if the reaction reliability
consistently and statistically significantly exceeded the false
alarm level. With different frequencies (37.7, 42.25, 53.57
GHz), intensities (from 5 to 15 mW/cm2) and bandwidths, the
radiation was detected by 30 to 80% of examinees. Interestingly,
37.7 GHz radiation at 15 mW/cm2 was detected by far fewer people
than 42.25 GHz at 5 mW/cm2. The reaction latency was usually
between 40 and 50 s. It was speculated that MMW perception could
involve some types of mechanoreceptors and nociceptors.
3.2 Teratogenic
effects of MMW
The only study
of MMW teratogenic effects was performed in Drosophila
flies by Belyaev et al. [1990]. Embryos of the blastula and
gastrula stages (2.5-3 hours after laying) and pupas at the
stage of imago tissue formation were exposed in a waveguide at
46.35, 46.42, or 46.50 GHz, for 4-4.5 hours at 0.1 mW/cm2,
followed by incubation at 25 oC. Irradiation at 46.35
GHz, but not at 46.42 or 46.50 GHz, caused marked effects.
Exposure of pupas increased incidence of morphological
abnormalities 2-4.5 times (p<0.05), but did not influence
imago survival. Exposure of embryos decreased survival by about
30% (p<0.05) and enhanced morphological abnormalities, but
this effect was rather variable. Supposedly, MMW disturbed
DNA-protein interactions which determine the realization of the
ontogenetic program.
3.3 High-power
MMW effects
Over the past
several years, physiological effects of high levels of MMW
radiation have been intensively studied by Frei et al. [1995],
Frei and Ryan [1995], and Ryan et al. [1996, 1997]. In ketamine
anesthetized rats, exposure to 35 GHz, 75 mW/cm2 radiation
(12-13 W/kg whole body SAR) increased the subcutaneous
temperature by 0.25 oC/min and the colonic
temperature by 0.08 oC/min. Concurrently with the
hyperthermia, mean arterial blood pressure first increased
slightly and then fell until the point of death. Hypotension was
accompanied by vasodilatation in the mesenteric vascular bed,
which was similar to heat stroke induced by environmental
heating. However, the onset of vasodilatation and hypotension
occurred at much lower colonic temperatures (< 37.5 oC
versus > 41.5 oC). The lethal effect became
irreversible when the mean arterial pressure fell to 75 mm Hg,
even if the exposure was discontinued. Most intriguing,
pathological examination of the skin of lethally exposed animals
revealed no significant thermal damage or full-thickness burn,
and cardiovascular responses did not mimic those observed in
traditional burn models. Searching for physiological mechanisms
mediating the hypotensive response, the authors established that
nitric oxide, platelet-activating factor, and histamine do not
contribute to it. Exposure of rats at 94 GHz at a similar SAR
produced a comparable pattern of heating and cardiovascular
responses.
3.4
Experimental MMW therapy: animal studies.
Except those
cited above, virtually all animal studies on MMW effects have
been related to various issues of MMW therapy, such as stress
relief, wound healing, tissue regeneration, and protection from
ionizing radiations. Paradoxically, these animal studies are
still less numerous and comprehensive than reports on MMW
therapy in humans. Many applications of the MMW therapy seem to
have never been adequately tested in animal experiments. For
example, we counted 38 publications (including meeting
abstracts) on various clinical aspects of the MMW therapy for
peptic ulcers, but could find just one animal study on this
subject. It appears that, in some cases, animal studies did not
precede the clinical use of MMW (as one would expect), but were
carried out to create experimental justification for already
reported clinical data.
3.4.1 Tissue
repair and regeneration.
Among possible therapeutic applications of MMW, the more
plausible and understandable is treatment of surface lesions
(wounds, burns, ulcers), which are directly reachable by the
radiation. Indeed, this application has gained sound
experimental support in several independent works. Other studies
have demonstrated that repair of deep tissues (bone and nerve)
could also be stimulated by MMW, suggesting that such effects
are mediated by activation of the organism's own recovery
mechanisms.
Zemskov et al.
[1988] studied MMW effects on healing of skin wounds in rabbits.
The animals were randomly assigned to four groups; wounds in
groups 1 and 2 were kept aseptic, and in groups 3 and 4 were
infected with a pathogenic Staphylococcus. The wound
surface in groups 1 and 3 was treated with 37 or 46 GHz CW MMW
at 1 mW/cm2 for 30 min twice a day, for 5 days. A horn
irradiator was placed 2-5 mm over the wound surface. Rabbits in
groups 2 and 4 served as untreated controls. MMW decreased
swelling of wound edges, hyperemia, and infiltration, and
rapidly reduced the wound area in the first 24 hours; it also
stimulated phagocytosis and reduced bacterial contamination.
Complete healing of aseptic wounds in the exposed group took 2.9
days less than in the control group. Infected wounds cleaned up
and filled with granulation tissue on days 14-16 in the exposed
group, and only on days 21-23 in the respective control.
A similar
protocol was employed in a double-blind replicative study by
Korpan et al. [1994]. Rabbits with 4 x 6 cm cutaneous wounds
were randomly divided into 4 groups of 18 animals each. The
wounds of two groups were rendered septic by inoculating them
with 109 Staphylococcus cells. The wound was
exposed for 30 min a day (37 GHz CW, 1 mW/cm2), for 5 days in
one aseptic group and for 7 days in a septic one. The horn
aperture was 10 cm from the wound surface. The other two groups
were sham-irradiated and served as aseptic and septic controls.
In irradiated animals, wound edge swelling and hyperemia
subsided faster, and granulation tissue filled the wound
earlier. On day 7, for example, the surface area of septic
wounds decreased by 19% in the control group, and by 44% in the
irradiated group. The mean daily decrease in wound surface area
of the irradiated animals was significantly greater than in the
controls: 7.9% versus 3.2% in the aseptic groups, and 6.3%
versus 2.7% in the septic groups (p<0.05). Exposures
stimulated phagocytic activity of neutrophils and decreased the
blood level of circulating immune complexes. Thus, MMW
irradiation enhanced both septic and aseptic wound healing and
stimulated immune function.
Detlavs et al.
[1993, 1994, 1995, 1996] have extensively studied MMW effects on
the composition of granulation fibrous tissue (GFT) during early
stages of wound healing. Their experiments were performed in
rats with incised full-thickness dermal wounds. The injured area
was exposed for 30 min daily for 5 days at 10 mW/cm2 (53.53 or
42.19 GHz CW, or 42.19 GHz with ± 200 MHz frequency
modulation). Control animals underwent the same manipulations,
but were sham exposed. GFT samples from the wound were taken for
analysis on the 7th day. CW irradiation significantly decreased
the GFT contents of glycoproteins (hexosamines, hexoses, and
sialic acids), indicating a suppression of the inflammatory
process. In contrast, modulated MMW enhanced the inflammation
and increased the production of glycoproteins. CW exposure
decreased the GFT content of hydroxyproline, which is a marker
for total collagen, to 79-85% of the control (p<0.01), while
the modulated regimen increased it to 126-133% (p<0.001). CW
radiation at 53.53 GHz usually was more effective than at 42.19
GHz. Both the anti- and pro-inflammatory effects of MMW could be
useful in clinical practice. CW exposure can be recommended for
early stages of the wound healing when control of the
inflammatory reaction is desirable. Modulated radiation can be
used to promote ultimate recovery in slow-healing wounds, or in
cases of healing deceleration in the late stages of tissue
repair.
Ragimov et al.
[1991] used MMW to stimulate the repair of an experimentally
produced bone defects in rabbits. A hole 6 mm in diameter was
drilled in the lower jaw bone, and the wound was sutured. The
first exposure for 30 or 60 min was performed the next day, and
six more exposures were done over the next two weeks. The shaven
nape was exposed from a horn (2-cm2 aperture) placed 3-4 mm from
the skin (5.6 mm wavelength, 25 mW output power). Control
animals were handled similarly. Five animals from each group
were killed every week for morphological and roentgenographic
analysis of bone repair. One week after the operation, the
extent of reparative osteogenesis was the same in all the
groups. Later on, the regeneration was faster in exposed
animals, particularly in the group with 60-min exposures. By the
end of the observation period (28 days), the appearance of the
traumatic defect in the control group was nearly the same as it
was in exposed animals on day 21. Hence, irradiation shortened
the bone repair time by approximately one week.
Kolosova and
co-authors [1996a] established that MMW treatment could promote
regeneration of a damaged peripheral nerve. The sciatic nerve in
40 rats was transected in the thigh region and sutured. Skin
over the injury area was irradiated every third day for 10 min
with 4-mW/cm2, 54-GHz radiation for 7 or 20 days; control rats
were sham irradiated. Exposures did not change the skin
temperature (0.1 oC accuracy). Upon the completion of
the treatment course, the nerve was isolated, and the extent of
regeneration was assessed electrophysiologically. After the
7-day course, the regeneration distance was 4.8 mm versus 3.0 mm
in the controls (p>0.05). After the 20-day course, the effect
became statistically significant: the regeneration distance was
18.4 ± 0.4 mm versus 14.0 ± 1.4 mm (p<0.01). The nerve
conduction velocity also significantly increased, while the
amplitude and duration of the action potential were not
affected.
In a
continuation study [Kolosova et al., 1996b], the same
irradiations were performed for two weeks after the injury, and
the nerve was isolated for examination in 5 months. Indices of
regeneration were the compound action potential amplitude and
conduction velocity at different distances (5 to 19 mm) distal
from the suture. Both parameters were higher in the exposed
animals. For example, 19 mm from the suture, the velocity was
20.4 ± 0.9 m/s versus 15.5 ± 0.9 m/s in controls (p<0.05),
and the amplitude was 313 ± 34 m V versus 156 ± 15 m V
(p<0.001). Hence, exposures not only stimulated the growth of
nerve fibers, but facilitated their functional maturation as
well.
3.4.2 Tumor
growth and development.
Experiments by Smirnov et al. [1991] were designed to evaluate
the possible use of MMW for the treatment of cancer. VMR tumor
cells with a high metastasizing activity were inoculated into
the tibial muscle of A/SNL line mice at 5 x 105 cells/animal.
Exposure for 5 days, one hour daily (12.5 mW/cm2, 7.09-7.12 mm
wavelength, 50 Hz modulation), increased the average life span
by 17% compared with sham controls. The number of visible
metastases decreased by more than 50% in lungs, liver, kidney,
and adrenal glands, but not in lymph nodes. The authors noted
variability of the MMW effect, and, in one series, exposure even
intensified metastasizing.
Chernov et al.
[1989] attempted to suppress malignant growth by extremely-high
peak power nanosecond MMW pulses. Rats were exposed immediately
after inoculation with 10, 25, or 50 (x 103) Walker tumor cells,
and two more times during the next two days. Each exposure
consisted of 43 pulses delivered with 40-s intervals. Two
regimens were tested: 8 mm wavelength at 4-5 MW output power,
yielding 20 kV/cm E-field level at the skin surface, and 5 mm,
8-10 MW, 30 kV/cm, respectively. The first of these regimens
retarded tumor growth 1.5 times and increased the life span by
17-25 days after the doses of 10 and 25 (x 103); the other
regimen was less effective. The antitumor effect was presumably
mediated by stimulation of immune system, namely the so-called
skin-associated lymphoid tissue. Preliminary studies with
exposure prior to tumor inoculation showed that MMW retarded the
tumor growth nearly twofold.
Because of
concern about possible adverse effects of MMW use in cancer
patients, Brill' and Panina [1994] studied the transplantability
and growth of a benign tumor (mammary fibroadenoma) in rats. Two
tumor pieces were implanted to the right and left sides through
a cut in the middle of the abdomen. In 20 of 49 operated
animals, tissues in the cut were exposed to MMW (42.0-43.3 GHz
band) for 15 min before the implantation, the other animals
served as control. In 3 weeks, 39 out of 58 tumors (67.3%)
resolved in the control group, but only 11 out of 40 (27.5%)
resolved in the exposed animals (p<0.001). The percentages of
stable and growing unresolved tumors in both the groups were the
same. Hence, a single MMW exposure of the implantation area
increased tumor transplantability, though did not affect its
proliferation.
3.4.3 Stress
alleviation and prevention effects. Temur'iants
and Chuyan [1992] demonstrated that MMW can alleviate
immobilization-induced stress in rats. The authors established
that this MMW effect differed in specimens with different
characteristic levels of exploratory activity, as evaluated by
an open-field testing. In further studies, the open-field
testing was always done prior to stressing and MMW exposures, to
divide the population into appropriate groups.
One of these
studies [Temur'iants et al., 1993] was performed on 350 animals
divided into groups with a low (LA), medium (MA) and high (HA)
activity. Each group was subdivided into 5 groups; group 1 was
cage control, and groups 2-5 were housed for 9 days in
individual boxes restricting their motion. Animals in groups 3-5
received daily 30-min MMW exposures of the occipital area, left
hip, or right hip, respectively (5.6-mm wavelength, 10 mW/cm2).
Stress severity was quantified by indices of the
"nonspecific resistivity" of the organism, which
included the contents of lipids and peroxidase in neutrophils,
and activities of succinate and alpha-2-glycerophosphate
dehydrogenases in lymphocytes. A typical stress reaction
developed in unexposed MA rats: by days 6-9, the contents of
lipids and peroxidase decreased by 21-24%, and the activity of
dehydrogenases fell by 36-46%. Occipital or right hip MMW
irradiation prevented the stress reaction in MA rats, while the
left hip exposure was not effective. The immobilization stress
was the most pronounced in unexposed HA animals; MMW exposures
of the left hip or occipital area prevented stress, while
exposures of the right hip had little effect. In LA animals, the
stress reaction was relatively weak, and all the types of MMW
treatment alleviated it.
The next study
employed 640 albino rats, all with a medium level of locomotor
activity [Temur'iants et al., 1994]. The same indices as above
were compared in four groups: cage control, hypokinesia without
exposures, exposures without hypokinesia, and both. Occipital
area was exposed for 30 min/day, 9 days at either 5.6 or 7.1 mm
wavelength. Exposures without hypokinesia strongly activated
succinate dehydrogenase (up to twofold, p<0.05). Irradiation
at 5.6 mm (but not at 7.1 mm) increased the activities of acid
and alkaline phosphatases and glycerophosphate dehydrogenase by
20-30%. Both wavelengths prevented or reversed stress-induced
changes, 5.6 mm was more effective. Further experiments with 5.6
mm radiation established that exposures for 15 min/day were less
effective than for 30 min/day, and, paradoxically, increasing
the exposure duration to 60 min/day eliminated its anti-stress
effect.
A similar
exposure technique was independently used by Arzumanov et al.
[1994]. The occipital area was exposed at 5.6 mm simultaneously
with immobilization of the rat's head for 60 min/day for 10
days. This stressing suppressed feeding and sexual behavior, and
increased the motor activity in a swimming test to the same
degree in exposed and unexposed groups. The authors hypothesized
that the immobilization stress was too severe and might mask MMW
effects, so in the next series rats were immobilized and exposed
for only 30 min/day for 9 days. The stress effect was assessed
by the electric shock threshold, free-access water consumption,
and Vogel's choice test (consumption of water when each attempt
to drink is accompanied by an electric shock). Immobilization
without exposure decreased threefold the number of attempts to
drink in Vogel's test; but, when immobilization was combined
with MMW exposures, this index remained the same as in cage
controls. The shock threshold and free-access water consumption
were not changed by MMW.
It is
interesting to note some parallelism in the above two studies.
Using the same exposure procedures, but different protocols and
endpoints, both research groups established that there is an
anti-stress effect of a 30-min irradiation, but there is no such
effect if the exposure duration is 60 min. The decreased
efficacy of a more prolonged MMW irradiation has been observed
in some other clinical and experimental studies as well, but
this unusual time dependence has not been discussed or explained
yet.
3.4.4. Combined
MMW and ionizing radiation exposure. Gubkina
et al. [1996] researched whether low-intensity MMW can alleviate
the effect of X-rays in rats. The abdominal area was shaved and
exposed to MMW in a frequency-sweep regimen (38 to 53 GHz) at 7
mW/cm2 for 23 days, 30 min/day. Controls not treated by MMW
underwent all the same manipulations, including shaving.
Exposures to 150 keV X-rays were performed daily during the last
8 days of the MMW course up to a total dose of 24 Roentgen.
Blood serum and brain tissue samples were collected the next day
after the end of exposures. MMW alone did not alter the serum
glucose level (6.24± 0.79 mM versus 6.53± 0.80 mM in
controls); X-ray exposure increased it to 10.37± 0.75 mM
(p<0.05), but combining X-rays with MMW prevented this rise
(6.81± 0.37 mM). MMW decreased the content of the soluble form
of the acidic glial fibrillar protein (s-AGFP) 1.5-2 times
(p<0.05) in all analyzed structures of the brain (cerebellum,
midbrain, and medulla oblongata), and did not change the content
of its fibrillar form (f-AGFP). X-rays decreased the levels of
both forms of the protein 2-3 times. After combined treatment
with MMW and X-rays, both s- and f-AGFP levels did not differ
from controls, and were significantly (p<0.05 and p<0.01)
higher than after X-rays only. The authors concluded that MMW
alleviated the effect of X-rays at both cellular and organism
levels.
Two other
studies are of interest, although they are only brief reports
that do not contain essential experimental details. Kuzmanova
and Ivanov [1995] studied changes in the surface electrical
charge of erythrocytes after MMW and g -ray exposures in rats.
The shin of the right hind limb was exposed to 5.6 mm radiation
for 10 days, 20 min/day at 1.1 mW/cm2, followed with a 6 Gy
whole-body dose of 137Co g -rays. The surface charge
of erythrocytes was assessed from their electrophoretic mobility
(EPM) 3, 7, 14, 21, and 30 days after the exposures. The MMW
treatment alone had practically no effect, while g -rays alone
decreased EPM for the whole period of observation. When g
-irradiation was preceded by MMW, the EPM remained the same as
in controls. The authors concluded that MMW stabilized the
membrane structure and increased its resistivity to g
-radiation.
Tsutsaeva et
al. [1995] examined MMW-induced survival changes in mice after a
lethal dose of X-rays. Irradiation with pulse-modulated MMW at 1
m W/cm2 continued for 80 or 24 hours prior to X-ray exposure, or
was simultaneous with the X-ray exposure. All tested X-ray doses
(7, 7.5, and 8 Gy) were 100% lethal, with the average life span
of 6-8 days; the first fatalities occurred on days 4-6. MMW
treatment for 80 hours before 7 Gy of X-rays delayed the first
deaths until day 14; 50% of the population died within 30 days,
and 100% of the animals died by day 96. The MMW treatment for 24
hours appeared even more effective: first deaths occurred on day
8, 50% of the animals died within 30 days, but no more
fatalities were observed through day 96. Microwave irradiation
simultaneously with the X-rays (7 Gy) increased the survival and
life span of mice approximately 5-fold. The protective effect of
24-hour MMW pretreatment decreased with increasing X-ray dose to
7.5 Gy, and became insubstantial at 8 Gy.
3.5 MMW
therapy: clinical studies.
The first
clinical trials of MMW therapy began in 1977, and nowadays the
method has been officially approved by the Russian Ministry of
Health and is used widely. As mentioned in the
"Introduction" section, by 1995 over 3 million people
have been treated at more than a thousand specialized centers as
well as at regular hospitals [Lebedeva and Betskii, 1995].
3.5.1 General
issues of the MMW therapy. MMW
therapy involves repetitive local exposures of certain body
areas with low-intensity MMW. The area(s) to be exposed, the
radiation wavelength, and daily duration of procedures are
determined by the physician based on the disease and the
condition of the particular patient. The radiation intensity is
usually regarded as a less important variable. For most
diseases, the daily exposure varies from 15 to 60 min, and the
therapy lasts for 8-15 days.
Publications on
the clinical use of MMW are counted by hundreds, and many of
them have claimed that MMW monotherapy is more effective
(sometimes, far more effective) than conventional methods, such
as drug therapy, for a variety of diseases and disorders. In
some cases, MMW has helped the patients who had already tried
all other known therapies without success, and were considered
incurable. At the same time, MMW seldom caused any adverse
effects or allergies. MMW in combination with drug therapy
facilitated favorable effects and/or reduced adverse side
effects of drugs. Some authors reported that MMW might be highly
effective or not effective at all, contingent on the patient's
condition, individual sensitivity to MMW, and parameters of
irradiation. A few authors reported that MMW therapy was always
less effective than conventional techniques, and we found only
one clinical study saying that MMW therapy was not effective at
all [Serebriakova and Dovganiuk, 1989].
Diseases
reported to be successfully treated with MMW belong to rather
diversified groups. The most common applications of MMW are for
gastric and duodenal ulcers (about 25% of studies),
cardiovascular diseases, including angina pectoris,
hypertension, ischemic heart disease, infarction (about 25%),
respiratory sicknesses, including tuberculosis, sarcoidosis,
bronchitis, asthma (about 15%), and skin diseases, including
wounds, trophic ulcers, burns, atopic dermatitis (about 10%).
These percentages are approximate, because we could not cover
all clinical studies published, and because many authors
reported treatment of several diseases in one paper (so the sum
would be over 100%). Isolated studies claimed successful MMW
treatment for asthenia, neuralgia, diabetes mellitus,
osteochondrosis, acute viral hepatitis, glomerulonephritis,
alcoholism, etc. MMW were also used for alleviation of toxic
effects of chemotherapy in cancer patients, and in preventive
medicine and health resort therapy.
In most cases,
physicians use specialized MMW generators, which are produced
commercially by the medical equipment industry. These generators
operate at average radiation intensities of 10 mW/cm2 or less,
in CW or frequency-modulated regimens, at certain fixed
frequencies, or within a wide frequency band. Three models have
been used more often than all others together:
"Yav'-1-7,1" (7.1 mm wavelength, 42.19 GHz),
"Yav'-1-5,6" (5.6 mm, 53.53 GHz), and
"Electronica-KVCh" (4.9 mm, 59-63 GHz band). The
respective rates of using these devices are 36%, 31%, and 10%.
Different generators were often used within a single study to
compare their therapeutic efficacy, and more often than not, the
efficacy was different, depending on the disease and patients'
condition. Some authors used in vitro tests to determine
which wavelength is more suitable for a particular patient
before the onset of the therapy [Novikova et al., 1995].
However, we have been unable to identify references to the
original studies that had shown why the frequencies of 42.19,
53.53, and 59-63 GHz (and not others) should be used for
therapy.
In about 30% of
clinical studies, the radiation is applied to standard
acupuncture points or so-called biologically-active points. This
procedure is often combined with finding the individual
"resonance" frequency based on MMW-evoked
"sensations" of the patient (the method is called
"microwave resonance therapy"). In our opinion, this
procedure should be regarded as a variety of acupuncture
techniques, along with electropuncture, acupressure, etc.
Assuming the therapeutic efficacy of these techniques, it is no
surprise that MMW can be effective as well: irradiation at about
10 mW/cm2 can also stimulate acupuncture points by subtle
heating or thermal "micromassage". Clinical effects of
the "MMW-puncture" are nonspecific, meaning that they
are similar to those of traditional puncture-based techniques.
These effects are determined by the selection of acupuncture
points, intensity and duration of their stimulation, rather than
by using MMW or other means for the stimulation. Therefore,
studies employing the MMW-puncture seem to be of greater
interest for the acupuncture practice than for the
bioelectromagnetic science; such studies will be left beyond the
scope of the present review.
Other areas of
MMW exposure include sternum and xiphoid process, skin
projection of the diseased organ, large joints, and the surface
of wounds and ulcers. Once again, we could not identify the
studies that originally provided the rationale and experimental
proof for MMW exposure of these particular body areas. Except
for the surface lesions, the radiation is unable to penetrate to
diseased organs. This fact is understood and discussed by many
physicians, but no proven explanation of the MMW therapy has
been given yet.
Many clinical
studies do not conform to conventional quality criteria
(double-blind protocol, placebo treatment, adequate statistics,
etc.), but still others do, and a lot of matching results has
been provided by independent groups of investigators. Some
clinical data on the MMW efficacy are quite impressive, and a
few examples are given below (see a specialized review by
Rojavin and Ziskin [1998] for additional detail).
3.5.2 Examples
of MMW therapy.
Korpan and Saradeth [1995] performed a double-blind controlled
trial of MMW therapy for postoperative septic wounds. The study
group consisted of 141 patients, 31-83 yr old, with purulent
wounds after an abdominal surgery. The wounds were infected
mostly with Staphylococcus aureus and Bacteriodes
fragiles. MMW therapy with 1-mW/cm2, 37-GHz CW radiation was
employed in 71 patients. Wound surface and adjacent soft tissue
were exposed for 30 min/day for 7 days. The remaining 70
patients received placebo therapy from a similar but defective
MMW generator (neither patients nor physicians knew it was
defective). Radical surgical cleaning of the wounds was
performed regularly in both groups. The MMW-treated patients
showed 1.8 times more rapid wound clearance (5.6± 0.6 versus
10.2± 0.5 days in controls), 1.7 times earlier onset of wound
granulation (4.9± 0.2 versus 8.7± 0.4 days), and 1.8 times
earlier onset of epithelization (7.0± 0.4 versus 12.8± 0.6
days). The average daily decrease of wound surface area in the
treated patients was twice that of the controls (7.1% versus
3.2%). The authors concluded that low intensity MMW appears to
be an effective postoperative wound treatment.
Poslavsky
et al. [1989] employed MMW as a monotherapy in 317 patients with
duodenal and gastric ulcers. The ulcer diameter ranged from 0.3
to 3.5 cm, and the disease duration was from several months to
more than 10 years. The epigastric area was exposed at 10
mW/cm2, 5.6-mm wavelength for 30 min daily, excluding weekends,
until complete ulcer cicatrization. A comparable control group
of 50 patients received conventional drug therapy. The ulcers
cicatrized in 95.3% of MMW-treated patients, with mean healing
duration of 19.8 ± 0.45 days. The respective control group
values were substantially worse, namely 78% and 33.6 ± 1.12
days. The ulcer relapse rate was significantly lower after the
MMW therapy.
Megdiatov et
al. [1995] evaluated the efficacy of MMW therapy (42.2 GHz, 10
mW/cm2) in 52 patients with neuralgia. The radiation was applied
to areas where branches of the affected trigeminal nerve
approach the skin (10 exposures or sham exposures, 15 min each,
concurrently with medicinal therapy). Evident clinical
improvement (decrease of the incidence and severity of pain
attacks) was achieved in 19 out of 27 patients treated with MMW,
and only in 4 out of 25 patients receiving placebo exposures.
Liusov et al.
[1995] studied MMW therapy effects in 100 patients with unstable
angina pectoris (this is an intermediate condition between
stable angina pectoris and infarction, and is characterized by a
high risk of myocardial necrosis). The patients were divided
into 4 groups. Group 1 was treated by MMW only (10 exposures of
the right shoulder joint for 30 min/day, 7.1 mm); these patients
ceased taking any vasodilators and antianginal medicines. In
group 2, the same MMW therapy was combined with drugs
(beta-adrenergic antagonists, calcium blockers, organic
nitrates, etc.). Group 3 received the same drug therapy and
placebo exposures, and group 4 received the drug therapy only.
The therapy in groups 1 and 2 substantially decreased the rate
and severity of angina attacks, making it possible to reduce the
amount of nitroglycerin taken. It also decreased blood levels of
malonic dialdehyde and dienic conjugates, normalized T-helper
and T-suppresser ratio, reduced the diameter of venules, and
increased the diameter of arterioles. No significant improvement
of the lipid peroxidation system, immune status, or
microcirculation was achieved in groups 3 and 4.
Karlov and
co-authors [1991] used MMW in a combined therapy for cerebral
circulatory disorders. The 79 patients in the study were mostly
50-80 year old and suffered from hypertensive disease and/or
atherosclerosis; 61 patients were hospitalized for acute
ischemic cerebral infarction, 13 for a transient disorder of the
cerebral circulation, and 5 for circulatory encephalopathy.
Patients were divided into two comparable groups. Both groups
received the same drug therapy (hypotensive, anticoagulant,
cardiotonic, and other remedies), while only the first one was
also treated with MMW (10 days, 30 min/day, 4.9 mm wavelength).
Patients of the second group were sham-exposed under a
double-blind protocol. A favorable therapeutic effect was
reported in 70% of the patients in group 1 and in 40% in group
2. MMW procedures helped decrease blood pressure, normalize the
blood glucose level, and eliminate serum fibrinogen B.
The efficacy of
the MMW therapy is often illustrated by individual clinical
cases. Naumcheva [1994] described the history of a 54-year old
male patient, who had two myocardial infarctions within a 2-year
interval. He experienced severe attacks of angina both on
exertion and at rest and took up to 80 nitroglycerin tablets a
day (0.4 mg). Repeated courses of in- and outpatient treatment
with beta-adrenoblockers, nitrates, plasmapheresis, etc. had
little effect. Finally, he was hospitalized in a grave condition
with a third infarction. Conventional methods were ineffective,
so MMW therapy was ordered on day 10 after admission (7.1 mm
wavelength, for 30 min/day to the left border of sternum).
Cardialgia decreased after two exposures and nighttime pain
attacks ceased after seven procedures. The nitroglycerin intake
was decreased to 1-2 tablets/day after 12 exposures. After the
MMW course, the patient did not have angina attacks for 3-4
days, was able to walk up to 5 km a day, and was discharged in a
satisfactory condition. Another man, age 62, was admitted to
hospital with a severe macrofocal infarction, collapse,
extrasystolia, and acute insufficiency and aneurysm of the left
ventricle. Three days of intensive treatment still left the
patient in this critical condition. Even the first MMW
irradiation of sternum (5.6 mm wavelength, three 10-min
exposures with 5-min intervals) had a striking effect: it
arrested angina attacks and normalized sleep, and indices of
hemodynamics stabilized within 5 days of the MMW therapy. The
patient was discharged in a satisfactory condition and later
underwent two additional MMW courses as a preventive measure.
3.5.3 Side
effects of MMW therapy. As
a rule, MMW therapy is well tolerated by patients, and this is
regarded as one of its advantages over a drug therapy. Though
most investigators reported no negative reactions to MMW, others
observed them in up to 26% of patients [Golovacheva, 1995]. The
possibility of induction of adverse health effects by a local,
low-intensity MMW irradiation is of potential significance for
setting health and safety standards and requires special
attention.
Kuz'menko
[1989] summarized experience with MMW use in 200 patients with
cerebrovascular diseases, such as cerebral circulation
insufficiency, discirculatory encephalopathy, and cerebral
insult consequences. Irradiation of the sinocarotid zone at
various frequencies between 58 and 62 GHz, 0.3-1 mW/cm2, was
performed for 20 min/day or less, for 4 to 10 days. MMW therapy
facilitated recovery in 56-77% of patients with different
pathologies. However, it also caused adverse side effects,
including elevation of the blood pressure (9 cases), induction
of a diencephalic crisis or paroxysm during irradiation (7
cases), angina attacks (3 cases), fever (5 cases), and
enhancement of menstrual bleeding (6 cases). In hypertension
patients, MMW usually decreased blood pressure by 10-15 mm Hg,
but occasionally increased it by 20-30 mm Hg. The author
concluded that MMW can be successfully used in cerebrovascular
therapy, but possible complications must be taken into account.
Afanas'eva and
Golovacheva [1997] employed MMW therapy in 124 patients with
stage II essential hypertension (5.6 or 7.1 mm wavelength, CW,
10 mW/cm2, 10 procedures for 30 min each). Unfavorable
autonomous nervous system reactions (whole-body shivering,
sweating, heart pains along with skin paling or reddening) were
observed in 18 patients (15.5%). In two cases, these reactions
developed into hypertensive crises, which had to be arrested by
drug injections. In 33 patients (26.6%), MMW induced
fluctuations of the arterial blood pressure and enhanced
headaches. A temporary improvement after 4-5 exposures was
followed by an increase in both systolic (by 25 ± 7.0 mm Hg)
and diastolic (by 10.0 ± 2.0 mm Hg) blood pressure, which
required medicinal correction. General adverse reactions after
the entire MMW course (six patients; 4.8%) included
sleeplessness or sleep with distressful dreams, weakness,
emotional instability, and irritability. These manifestations
were not profound and disappeared without further treatment. The
authors emphasized that these adverse reactions were not
encountered in patients who received placebo exposures.
Gun'ko and
Kozshina [1993] tried MMW therapy in 528 patients with various
diseases (ulcerative disease, ischemic heart disease, essential
hypertension, bronchitis, pneumonia, and others). Exposures at
5.6 or 7.1 mm wavelength lasted from 15 to 60 min/day, from 5 to
18 days. Three patients, being treated for rheumatic
polyarthritis, psoriasis, and duodenal ulcer (without any
concurrent drug therapy), developed urticaria (hives) on the
5th-7th day of exposures. An itchy rash appeared first in the
abdominal and thoracic areas, and soon spread everywhere.
Nevertheless, the treatment of the main disease in all these
cases was successful. The rash disappeared 2-10 days after the
completion of the MMW therapy but reappeared during the repeated
MMW courses. The authors called for more studies of MMW effects
on the immune system.
DISCUSSION
In this review,
we have found that recent research in the MMW area covers a
variety of subjects. Profound MMW effects were established at
all biological levels, from cell-free systems, through cells,
organs, and tissues, to animal and human organisms. While trying
to avoid a general discussion of thermal versus non-thermal
mechanisms in this review, we nonetheless must note that many of
the reported effects were principally different from those
caused by heating, and their dose and frequency dependencies
often suggested nonthermal mechanisms. Regardless of the primary
mechanism, the possibility of significant bioeffects of a
short-term MMW irradiation at intensities at or below current
safety standards deserves consideration and further study.
The major
question about FSU publications in the MMW area is their
reliability. A number of studies cited here were performed at
the highest scientific level. Other studies, perhaps the
majority of those cited, were flawed, but may still bear
valuable information and should not be discarded without proper
analysis.
For example,
free-field dosimetry in the MMW band is a serious technical
problem. As of our knowledge, no commercially available probes,
even in the U.S., are rated for near-field measurements in the
MMW band. Therefore, it is not surprising that many
investigators, particularly clinicians, have had to rely on
manufacturer-specified field intensities, such as 10 mW/cm2 for
"Yav'-1" therapeutic generator. One may doubt if the
field actually was 5, 10, or 15 mW/cm2, but under no
circumstances could it exceed a spatial average of, say, 50
mW/cm2, which is beyond the generator's capabilities. Thus,
while the precise exposure parameters may not be known, a range
of possible exposure intensities may be estimated. With
understanding of this fact, the experimental data may still be
important and usable.
Another
widespread shortcoming of clinical studies is that MMW therapy
is compared to drug therapy, without using a sham-exposed
control group. MMW therapy was often reported to be more
effective than drugs, which could be a placebo effect; but if
this were the case, one would have to conclude that placebo was
more effective than modern drug therapy. This possibility could
certainly be true for certain patients and certain disorders,
but does not seem feasible for large populations and a wide
scale of diseases.
A further
source of skepticism about findings made by FSU scientists is
that they have not been replicated in the West. Replication is
much needed indeed, but it can hardly be anticipated without
adequate attempts. To our knowledge, only three laboratories
throughout the US (less than 10 scientists total) are currently
doing any research on MMW bioeffects, which is by no means
sufficient to match the amount and variety of the FSU research.
Besides, many cited studies are very recent (1995-1997), so
replication has yet to be expected.
With all the
diversity of the MMW research, and differences in studied
subjects and endpoints, some particulars appear to be common for
various situations and MMW effects. Considering these
particulars may be critical for replication studies:
1.
Individuals or groups in a population, which would usually be
regarded as uniform, may react to MMW in rather different or
even opposite ways. For example, Temur'iants et al. [1993, 1994]
divided the vivarium population of rats by their open-field
activity before performing exposures. Not only reactions to MMW,
but also reactions to immobilization stress, were very different
in animals with low, medium, and high activity levels. Pooling
all the data together, as well as neglecting the intrinsic
differences in the population, would have inevitably masked MMW
effects.
2.
There seem to exist unknown and uncontrolled factors that
determine the MMW sensitivity of a specimen or a population.
Irradiation could increase antibiotic resistivity in one
experiment and decrease it in the next one [Bulgakova et al.,
1996]; it increased the beating rate in one isolated heart and
decreased it in the other [Chernyakov et al., 1989]; MMW-therapy
usually decreased blood pressure, but eventually increased it
greatly [Kuz'menko, 1989]. As long as these changes exceeded the
"noise" level and were not produced by a sham
exposure, they can be regarded as MMW effects. Again, pooling
all data together, regardless of the direction of changes, could
easily mask an MMW effect.
3.
Even robust MMW effects may be well reproducible for a limited
time and then disappear. The effects of complete suppression or
200-400% enhancement of chloride transmembrane current in alga
cells were far beyond any spontaneous variations and could
hardly be confused with any artifact [Kataev et al., 1993].
However, both effects weakened and disappeared by the end of
winter without any apparent reason. MMW effects on isolated frog
nerve also disappeared in spring [Burachas and Mascoliunas,
1989], suggesting that MMW sensitivity may be somehow related to
the base level of metabolism.
4.
MMW effects could often be revealed only in subjects with
already some deviation from the "normal" state. MMW
caused little or no reactions in intact animals, but
significantly alleviated effects of immobilization, ionizing
radiation, etc. Many clinical studies claim that MMW therapy is
effective only when one or another kind of pathology is present,
while in a healthy organism MMW will not produce any reactions
(however, this thesis has not been adequately proven).
5.
Increased sensitivity and even hypersensitivity of individual
specimens to MMW may be real. Depending on the exposure
characteristics, especially wavelength, a low-intensity MMW
radiation was perceived by 30 to 80% of healthy examinees
[Lebedeva, 1993, 1995]. Some clinical studies reported MMW
hypersensitivity, which was or was not limited to a certain
wavelength [Golovacheva, 1995]. In a study by Afanas'eva and
Golovacheva [1997], adverse health reactions to MMW appeared
only in women (100%), only with a labile course of angina
pectoris (100%), and most of them were in the menopausal period
(66.7%). The authors suggested that this category of people is
particularly sensitive to MMW.
It is important
to note that, even with the variety of bioeffects reported, no
studies have provided evidence that a low-intensity MMW
radiation represents a health hazard for human beings. Actually,
none of the reviewed studies with low-intensity MMW even pursued
the evaluation of health risks, though in view of numerous
bioeffects and growing usage of MMW technologies this research
objective appears very reasonable. Such MMW effects as
alterations of cell growth rate and UV light sensitivity,
biochemical and antibiotic resistivity changes in pathogenic
bacteria, as well as many others are of potential significance
for safety standards. MMW therapy in many cases employs field
intensities comparable to or lower than allowed by current
safety standards; still, even local and short-term exposures
were reported to produce marked effects. It should also be
realized that biological effects of a prolonged or chronic MMW
exposure of the whole body or a large body area have never been
investigated. Safety limits for these types of exposure are
based solely on predictions of energy deposition and MMW
heating, but in view of recent studies this approach is not
necessarily adequate.
The
significance of MMW bioeffects for human health, considering
both safety limitations and possible clinical applications,
should be neither over- nor underestimated. It is, however, an
intriguing and potentially important area that needs to be
further explored. If this present review draws attention to the
MMW research and stimulates new studies, we will consider its
goal accomplished.
ACKNOWLEDGEMENTS
The work was
supported in part by the U.S. Army Medical Research and Materiel
Command and the U.S. Air Force Armstrong Laboratory under US
Army contract DAMD17-94-C-4069 awarded to McKesson BioServices.
The views expressed in this article are those of the authors and
should not be construed as reflecting the official policy or
position of the Department of the Army, Department of the Air
Force, Department of Defense, or the United States Government.
REFERENCES
Afanas'eva
TN, Golovacheva TV (1997): Side effects of the EHF-therapy for
essential hypertension. Zvenigorod, Russia: 11th Russian
Symposium "Millimeter Waves in Medicine and
Biology," April, 1997 (Digest of papers). Moscow: IRE
RAN, pp 26-28 (in Russian).
Akoev GN,
Avelev VD, Semen'kov PG (1992): Perception of the low-level
millimeter-range electromagnetic radiation by electroreceptors
of the ray. Dokladi Academii Nauk 322:791-794 (in Russian).
Alekseev SI,
Ziskin MC (1995): Millimeter microwave effect on ion transport
across lipid bilayer membranes. Bioelectromagnetics
16:124-131.
Arzumanov
YuL, Kolotygina RF, Khonichava NM, Tverytskaya IN, Abakumova
AA (1994): Animal study of the stress-protective effect of
electromagnetic radiation of the extremely-high-frequency
range. Millimetrovie Volni v Biologii i Meditcine 3:5-10 (in
Russian).
Belyaev IYa,
Alipov YD, Shcheglov VS, Polunin VA, Aizenberg OA (1994):
Cooperative response of Escherichia coli to the resonance
effect of millimeter waves at super low intensity. Electro
Magnetobiol 13:53-66.
Belyaev IY,
Shcheglov VS, Alipov YD, Polunin VA (1996): Resonance effect
of millimeter waves in the power range from 10-19
to 3 x 10-3 W/cm2 on Escherichia coli cells at
different concentrations. Bioelectromagnetics 17:312-321.
Belyaev IYa
(1992): Some biophysical aspects of the genetic effect of
low-intensity millimeter waves. Bioelectrochem Bioenerg
27:11-18.
Belyaev IYa,
Alipov YD, Polunin VA, Shcheglov VS (1993a): Evidence for
dependence of resonant frequency of millimeter wave
interaction with Escherichia coli K12 cells on haploid genome
length. Electro Magnetobiol 12:39-49.
Belyaev IYa,
Okladnova OV, Izmailov DM, Sheglov VS, Obukhova LK (1990):
Differential sensitivity of developmental stages to low-level
electromagnetic radiation of extremely ultrahigh frequency.
Dokl Akad Nauk SSSR [Ser B Geol Chim Biol] 12:68-70 (in
Russian).
Belyaev IYa,
Shcheglov VS, Alipov YeD, Radko SP (1993b): Regularities of
separate and combined effects of circularly polarized
millimeter waves on E. coli cells at different phases of
culture growth. Bioelectrochem Bioenerg 31:49-63.
Belyakov EV,
Kichaev VA, Poslavskii MV, Starshinina VA, Soboleva ES (1989):
Use of blood radiophysical parameters in the extremely
high-frequency range for diagnostic purposes. In Devyatkov ND
(ed): "Millimeter Waves in Medicine and Biology."
Moscow: Radioelectronica, pp 83-88 (in Russian).
Berezhinskii
LI, Gridina NIa, Dovbeshko GI, Lisitsa MP, Litvinov GS
(1993):Visualization of the effects of millimeter radiation on
blood plasma. Biofizika 38:378-384 (in Russian).
Berzhanskaya
LYu, Berzhanskii VN, Beloplotova OYu (1995): Effect of
electromagnetic fields on the activity of bioluminescence in
bacteria. Biofizika 40:974-977 (in Russian).
Betzky OV
(1992): Use of low-intensity electromagnetic millimeter waves
in medicine. Millimetrovie Volni v Biologii i Meditcine 1:5-12
(in Russian).
Brill' GE,
Panina NP (1994): Effect of millimeter waves on
transplantability and growth of tumors. Fizicheskaia Meditzina
4:25 (in Russian).
Brill' GE,
Apina OR, Belyanina CI, Panina NP (1993): Effect of low-level
extremely high-frequency radiation on the genetic activity of
polytene chromosomes of Chironomus plumosus. Fizicheskaia
Meditzina 3:69-71 (in Russian).
Brovkovich
VM, Kurilo NB, Barishpol'ts VL (1991) Action of
millimeter-range electromagnetic radiation on the CA pump of
sarcoplasmic reticulum. Radiobiologiia 31:268-271 (in
Russian).
Bulgakova VG,
Grushina VA, Orlova TI, Petrykina ZM, Polin AN, Noks PP,
Kononenko AA, Rubin AB (1996): Effect of millimeter-band
radiation of nonthermal intensity on the sensitivity of
staphylococcus to various antibiotics. Biofizika 41:1289-1293
(in Russian).
Burachas G,
Mascoliunas R (1989): Suppression of nerve action potential
under the effect of millimeter waves. In Devyatkov ND (ed):
"Millimeter Waves in Medicine and Biology". Moscow:
Radioelectronica, pp 168-175 (in Russian).
Chernov ZS,
Faikin VV, Bernashevskii GA (1989): Experimental study of the
effect of nanosecond EHF pulses on malignancies. In: Devyatkov
ND (ed): "Millimeter Waves in Medicine and Biology."
Moscow: Radioelectronica, pp 121-127 (in Russian).
Chernyakov
GM, Korochkin VL, Babenko AP, Bigdai EV (1989): Reactions of
biological systems of various complexity to the action of
low-level EHF radiation. In Devyatkov ND (ed):
"Millimeter Waves in Medicine and Biology". Moscow:
Radioelectronica, pp 141-167 (in Russian).
Dardalhon M,
Averbeck D, Berteaud AJ (1979): Determination of a thermal
equivalent of millimeter microwaves in living cells. J
Microwave Power 14:307-312.
Dardalhon M,
Averbeck D, Berteaud AJ (1981): Studies on possible genetic
effects of microwaves in prokaryotic and eukaryotic cells.
Radiat Environ Biophys 20:37-51.
Dardanoni L,
Torregrossa MV, Zanforlin L (1985): Millimeter wave effects on
Candida albicans cells. J Bioelectricity 4:171-176.
Detlav IE,
Shkirmante BK, Dombrovska LE, Pahegle IV, Slutskii LI (1993):
Biochemical parameters of developing granulo-fibrous tissue
after the effect of an extremely high-frequency
electromagnetic field. Millimetre Volni v Biologii i Meditcine
2:43-50 (in Russian).
Detlavs I,
Dombrovska L, Klavinsh I, Turauska A, Shkirmante BB, Slutskii
L (1994): Experimental study of the effect of electromagnetic
fields' in the early stage of wound healing. Bioelectrochem
Bioenerg 35:13-17.
Detlavs I,
Dombrovska L, Shkirmante B, Turauska A, Slutskii L (1996):
Some biological effects of mm-wave electromagnetic fields on
the granulation-fibrous tissue in a healing wound. Moscow,
Russia: 10th Russian Symposium "Millimeter Waves in
Medicine and Biology," April, 1995 (Digest of papers).
Moscow: IRE RAN, pp 117-119 (in Russian).
Detlavs I,
Dombrovska L, Turauska A, Shkirmante B, Slutskii L (1996):
Experimental study of the effects of radiofrequency
electromagnetic fields on animals with soft tissue wounds. Sci
Total Environ 180:35-42.
Enin LD,
Akoev GN, Potekhina IL, Oleiner VD (1992): Effect of extremely
high-frequency electromagnetic radiation on the function of
skin sensory endings. Patol Fiziol Eksp Ter (5-6):23-25 (in
Russian).
Fesenko EE,
Gluvstein AYa (1995) Changes in the state of water induced by
radiofrequency electromagnetic fields. FEBS Letters 367:53-55.
Fesenko EE,
Geletyuk VI, Kazachenko VN, Chemeris NK (1995): Preliminary
microwave irradiation of water solutions changes their channel
modifying activity. FEBS Letters 366:49-52.
Fesenko EE,
Geletyuk VI, Kazachenko VN, Chemeris NK (1995): Preliminary
microwave irradiation of water solutions changes their
channel-modifying activity. FEBS Lett 366:49-52.
Frei MR, Ryan
KL (1997): Circulatory failure resulting from sustained
millimeter wave irradiation. Brooks AFB, TX: Infrared Lasers
and Millimeter Waves Workshop "The Links Between
Microwaves and Laser Optics," January, 1997.
Frei MR, Ryan
KL, Berger RE, Jauchem JR (1995): Sustained 35-GHz
radiofrequency irradiation induces circulatory failure. Shock
4:289-293.
Fröhlich H
(1980): The biological effects of microwaves and related
questions. Adv Electronics Electron Phys 53:85-152.
Fröhlich H
(1988, ed): Biological coherence and response to external
stimuli. Springer-Verlag, Berlin, 265 p.
Furia L, Hill
DW, Gandhi OP (1986): Effect of millimeter-wave irradiation on
growth of Saccharomyces cerevisiae. IEEE Trans Biomed Eng
33:993-999.
Gandhi OP
(1983): Some basic properties of biological tissues for
potential biomedical applications of millimeter-waves. J
Microw Power 18:295-304.
Gapeev AB,
Chemeris NK, Fesenko EE, Khramov RN (1994): Resonance effects
of a low-intensity modulated EHF field. Alteration of the
locomotor activity of the protozoa Paramecium caudatum.
Biofizika 39:74-82 (in Russian).
Gapeev AB,
Safronova VG, Chemeris NK, Fesenko EE (1996): Modification of
the activity of murine peritoneal neutrophils by exposure to
millimeter waves at close and far distances from the emitter.
Biofizika 41:205-219 (in Russian).
Geletyuk VI,
Kazachenko VN, Chemeris NK, Fesenko EE (1995): Dual effects of
microwaves on single Ca2+-activated K+
channels in cultured kidney cells Vero. FEBS Lett 359:85-88.
Golant MB
(1989): Resonance effect of coherent millimeter-band
electromagnetic waves on living organisms. Biofizika
34:1004-1014 (in Russian).
Golant MB,
Kuznetsov AP, Boszhanova TP (1994): Mechanisms of
synchronization of the yeast cell culture by the action of EHF
radiation. Biofizika 39:490-495 (in Russian).
Golovacheva
TV (1995): EHF therapy in complex treatment of cardiovascular
diseases. Moscow, Russia: 10th Russian Symposium
"Millimeter Waves in Medicine and Biology," April,
1995 (Digest of papers). Moscow: IRE RAN, pp 29-31 (in
Russian).
Gos P, Eicher
B, Kohli J, Heyer W-D (1997): Extremely high frequency
electromagnetic fields at low power density do not affect the
division of exponential phase Saccharomyces cerevisiae cells.
Bioelectromagnetics 18:142-155.
Grundler W
(1983): Biological effects of RF and MW energy at molecular
and cellular level. In Rindi A, Grandolfo M, Michaelson SM
(eds): "Biological Effects and Dosimetry of Nonionizing
Radiation. Radiofrequency and Microwave Energies." New
York: Plenum Press, pp 299-318.
Grundler W.
and Kaiser F (1992): Experimental evidence for coherent
excitations correlated with growth. Nanobiology 1:163-176.
Grundler W,
Jentzsch U, Keilmann F, Putterlik V (1988): Resonant cellular
effects of low intensity microwave.In Fröhlich H (ed):
"Biological Coherence and Response to External
Stimuli". Berlin, Springer-Verlagn, pp 65-85.
Grundler W,
Keilman F, Froehlich H (1977): Resonant growth rate response
of yeast cells irradiated by weak microwaves. Phys Letters
62A:463-466.
Grundler W,
Keilman F, Putterlik V, Strube D (1982): Resonant-like
dependence of yeast growth rate on microwave frequencies. Br J
Cancer 45:206-208.
Gubkina EA,
Kushnir AE, Bereziuk SK, Potapov VA, Lepekhin EA (1996):
Effects of low-intensity electromagnetic radiation of
extremely high-frequency on the animal organism in combination
with whole-body low-dose X-ray irradiation. Radiats Biol
Radioecol 36:722-726 (in Russian).
Gun'ko VT,
Kozshina NM (1993): Some complications of extremely
high-frequency therapy. Millimetrovie Volni v Biologii i
Meditcine 2:102-104 (in Russian).
Kaiser F
(1995): Coherent oscillations – their role in the
interaction of weak ELM-fields with cellular systems. Neural
network World 5:751-762.
Karlov
VA, Rodshtat IV, Kalashnikov IuD, Kitaeva LV, Khokhlov IuK
(1991): Experience with using extremely high frequency
radiotherapy of the millimeter wave range in cerebrovascular
disorders. Sov Med 3:20-21 (in Russian).
Kataev AA,
Alexandrov AA, Tikhonova LL, Berestovsky GN (1993):
Frequency-dependent effects of the electromagnetic millimeter
waves on the ion currents in the cell membrane of Nitellopsis:
nonthermal action. Biofizika 38:446-462 (in Russian).
Kazbekov EN,
Vyacheslavov LG (1987): Effects of microwave irradiation on
some membrane-related processes in bacteria. Gen Physiol
Biophys 6:57-64.
Khizhnyak EP,
Ziskin MC (1996): Temperature oscillations in liquid media
caused by continuous (nonmodulated) millimeter wavelength
electromagnetic irradiation. Bioelectromagnetics 17:223-229.
Khramov RN,
Sosunov EA, Koltun SV, Ilyasova EN, Lednev VV (1991):
Millimeter-wave effects on electric activity of crayfish
stretch receptors. Bioelectromagnetics 12:203-214.
Khramov RN,
Sosunov EA, Koltun SV, Ilyasova EN, Lednev VV (1991):
Millimeter-wave effects on electric activity of crayfish.
Bioelectromagnetics 12:203-214.
Kolosova LI,
Akoev GN, Avelev VD, Riabchikova OV, Babu KS (1996a): Effect
of low-intensity millimeter wave electromagnetic radiation on
regeneration of the sciatic nerve in rats. Bioelectromagnetics
17:44-47.
Kolosova LI,
Akoev GN, Riabchikova OV, Avelev VD (1996b): The effect of
low-intensity millimeter-range electromagnetic radiation on
the functional recovery of the damaged sciatic nerve in rat.
Fiziol Zh Im I M Sechenova 82: 85-90 (in Russian).
Korpan NN,
Saradeth T (1995): Clinical effects of continuous microwave
for postoperative septic wound treatment: a double-blind
controlled trial. Am J Surg 170:271-276.
Korpan NN,
Resch K-L, Kokoschinegg P (1994): Continuous microwave
enhances the healing process of septic and aseptic wounds in
rabbits. J Surg Res 57: 667-671.
Kotrovskaia
TI (1994): Sensory reactions evoked by weak electromagnetic
stimuli in humans. Millimetrovie Volni v Biologii i Meditcine
3:32-38 (in Russian).
Kremer F,
Santo L, Poglitsh A, Koschnitzke C, Behrens H. and Genzel L
(1988): The influence of low intensity millimetre waves on
biological systems. In Fröhlich H (ed): "Biological
Coherence and Response to External Stimuli." Berlin:
Springer-Verlag, pp 86-101.
Kudryashova
VA, Zavizion VA, Khurgin YuV (1995): Effects of stabilization
and destruction of water structure by amino acids. Moscow,
Russia: 10th Russian Symposium "Millimeter Waves in
Medicine and Biology," April, 1995 (Digest of papers).
Moscow: IRE RAN, pp 213-215 (in Russian).
Kuzmanova M,
Ivanov St (1995): Effect of millimeter waves and
gamma-radiation on the surface electrical charge of
erythrocyte membranes. In: "Millimeter Waves in Medicine
and Biology," Digest of papers of the 10th Russian
Symposium with International Participation, 24-26 April,
Moscow, Russia, pp 111-112 (in Russian).
Kuz'menko VM
(1989): Indications and contraindications to the use of
microwave resonance therapy (MRT) in patients with
cerebrovascular diseases. Kiev, Ukraine: First All-Union
Symposium with International Participation "Fundamental
and Applied Aspects of the Use of Millimeter Electromagnetic
Radiation in Medicine," May, 1989, pp 272-273 (in
Russian).
Lebedeva NN,
Betskii OV (1995): Application of low intensity millimeter
waves in medicine. Boston, MA: 17th Annual Meeting of the
Bioelectromagnetics Society, June, 1995, p 14.
Lebedeva NN
(1995): Neurophysiological mechanisms of biological effects of
peripheral action of low-intensity nonionizing electromagnetic
fields in humans. Moscow, Russia: 10th Russian Symposium
"Millimeter Waves in Medicine and Biology," April,
1995 (Digest of papers). Moscow: IRE RAN, pp 138-140 (in
Russian).
Lebedeva NN
(1993): Sensor and subsensor reactions of a healthy man to
peripheral effects of low-intensity millimeter waves.
Millimetrovie Volni v Biologii i Meditcine 2:5-23 (in
Russian).
Levina MZ,
Veselago IA, Belaya TI, Gapochka LD, Mantrova GM, Yakovleva MN
(1989): Influence of low-intensity VHF irradiation on growth
and development of protozoa cultures. In Deyatkov ND.(ed):
"Millimeter Waves in Medicine and Biology" Moscow:
Radioelectronica, pp 189-195 (in Russian).
Litvinov GS,
Gridina NYa, Dovbeshko GI, Berezhinsky LI, Lisitsa MP (1994):
Millimeter wave effect on blood plasma solution. Electro
Magnetobiol 13:167-174.
Liusov
VA, Volov NA, Lebedeva AYu, Kudinova MA, Schelkunova IG,
Fedulayev YuN (1995): Some mechanisms of the effect of
millimeter-range radiation on pathogenesis of unstable angina
pectoris. Moscow, Russia: 10th Russian Symposium
"Millimeter Waves in Medicine and Biology," April,
1995 (Digest of papers). Moscow: IRE RAN, pp 26-27 (in
Russian).
Logani MK,
Ziskin MC (1996): Continuous millimeter-wave radiation has no
effect on lipid peroxidation in liposomes. Radiation Research
145:231-235.
Megdiatov RS,
Vasilenko AM, Arkhipov VV, Kislov VYa, Kolesov VV, Smirnov VF
(1995): Use of a "Sharm" therapeutic-diagnostic
system in complex therapy of trigeminal nerve neuralgia.
Moscow, Russia: 10th Russian Symposium "Millimeter Waves
in Medicine and Biology," April, 1995 (Digest of papers).
Moscow: IRE RAN, pp 83-84 (in Russian).
Mikhno LE,
Novikov SA (1992): The mechanism of the therapeutic action of
millimeter electromagnetic waves and their importance in
treating cardiovascular diseases (a review of the literature).
Vrach Delo 10:14-18 (in Russian).
Mudrick DG,
Golant MB, Izvol'skaia VE, Slutzkii EM, Oganezova RA (1995):
Chemoluminescence of human blood leukocytes after exposure to
a low-intensity extremely-high frequency electromagnetic
field. Moscow, Russia: 10th Russian Symposium "Millimeter
Waves in Medicine and Biology," April, 1995 (Digest of
papers). Moscow: IRE RAN, pp 109-111 (in Russian).
Naumcheva NN
(1994): Effect of millimeter waves on ischemic heart disease
patients. Millimetrovie Volni v Biologii i Meditcine 3:62-67
(in Russian).
Novikova LN,
Kaminskaia GO, Efimova LN (1995): Significance of the
functional state of blood phagocytes in the choice of optimal
regime of EHF therapy of patients with pulmonary tuberculosis.
Probl Tuberk 6:17-20 (in Russian).
Osepchuk JM,
Petersen, RC (1997): Critical reviews of millimeter-wave
athermal effect studies relative to microwave engineering
principles. Brooks AFB, TX: Infrared Lasers and Millimeter
Waves Workshop "The Links Between Microwaves and Laser
Optics," January, 1997..
Pakhomov AG,
Prol HK, Mathur SP, Akyel Y, Campbell CBG (1997a): Search for
frequency-specific effects of millimeter-wave radiation on
isolated nerve function. Bioelectromagnetics 18:324-334.
Pakhomov AG,
Prol HK, Mathur SP, Akyel Y, Campbell CBG (1997b):
Frequency-specific effects of millimeter wavelength
electromagnetic radiation in isolated nerve. Electro
Magnetobiol 16: 43-57.
Pakhomov AG,
Prol HK, Mathur SP, Akyel Y, Campbell CBG (1997c): Role of
field intensity in the biological effectiveness of millimeter
waves at a resonance frequency. Bioelectrochem Bioenerg
43:27-33.
Pakhomova ON,
Pakhomov AG, Akyel Y (1997): Effect of millimeter waves on
UV-induced recombination and mutagenesis in yeast.
Bioelectrochem Bioenerg 43:227-232.
Poslavsky
MV, Korochkin IM, Zdanovich OF (1989): Experience with
application of millimeter-range radiation for treatment and
prophylactics of stomach and duodenal ulcer. Vopr Kurortol
Fizioter Lech Fiz Kult 4:31-36 (in Russian).
Postow E,
Swicord M.L (1986): Modulated fields and "window"
effects. In Polk C, Postow E (eds): "Handbook of
Biological Effects of Electromagnetic Fields." Boca
Raton, FL: CRC Press, Inc. pp 425-460.
Potekhina IL,
Akoyev GN, Yenin LD, Oleyner VD (1992): Effects of
low-intensity electromagnetic radiation in the millimeter
range on the cardio-vascular system of the white rat. Fiziol
Zh [formerly Fiziol Zh SSSR] 78: 35-41 (in Russian).
Ragimov, ChR,
Ter-Asaturov GP, Golant MB, Rogov KA, Balakireva LZ (1991):
Stimulation of reparative osteogenesis by electromagnetic
oscillations in the millimeter range in traumatic effects of
the lower jaw in experimental animals. Biull Eksp Biol Med
111:436-439 (in Russian).
Rebrova TB
(1992): Effect of millimeter-range electromagnetic radiation
on the vital activity of microrganisms. Millimetrovie Volni v
Biologii i Meditcine 1:37-47 (in Russian).
Rodshtadt IV
(1993): Physiological basis for some immune effects of
millimeter-range radiation action on skin. Millimetrovie Volni
v Biologii i Meditcine 2:24-35 (in Russian).
Rojavin MA,
Ziskin MC (1995): Effect of millimeter waves on survival of
UVC-exposed Escherichia coli. Bioelectromagnetics 16:188-196.
Rojavin MA,
Ziskin MC (1998): Medical application of millimetre waves. Q J
Med 91 (in press).
Roshchupkin
DI, Kramarenko GG, Anosov AK (1996): Effect of extremely high
frequency electromagnetic radiation and ultraviolet radiation
on aggregation of thymocytes and erythrocytes. Biofizika
41:866-869 (in Russian).
Roshchupkin
DI, Kramarenko GG, Anosov AK, Golant MB (1994): Changes in the
aggregation ability of rabbit thymocytes under the combined
effect of UV-radiation and extremely high frequency radiation.
Biofizika 39:1046-1050 (in Russian).
Ryakovskaya
ML, Shtemler VM (1983): Absorption of electromagnetic waves of
millimeter range in biological preparations with a plane-layer
structure. In: Devyatkov ND (ed): "Effect of Nonthermal
Action of Millimeter Radiation on Biological Subjects."
Moscow: USSR Academy of Sciences, pp 172-181 (in Russian).
Ryan KL, Frei
MR, Berger RE, Jauchem JR (1996): Does nitric oxide mediate
circulatory failure induced by 35-GHz microwave heating? Shock
6:71-76.
Ryan KL, Frei
MR, Jauchem JR (1997): Circulatory failure induced by 35 GHz
microwave heating: effects of chronic nitric oxide synthesis
inhibition. Shock 7:70-76.
Sazonov AYu,
Zamuraev IN, Lukashin VG (1995): Effect of the extremely high
frequency electromagnetic radiation on bush-like receptors of
frog bladder. Fiziol Zh Im I M Sechenova 81:46-49 (in
Russian).
Serebriakova
SN, Dovganiuk AP (1989): The treatment of patient with peptic
ulcer using millimeter-range waves. Vopr Kurortol Fizioter
Lech Fiz Kult 4:37-38 (in Russian).
Shestopalova
NG, Makarenko BI, Golovina LN, Timoshenko YuP, Baeva TI,
Vinokurova LV, Miroshnichenko VS (1995): Modification of
synchronizing effect of millimeter waves on first mitoses by
different temperature regimens of germination. Moscow, Russia:
10th Russian Symposium "Millimeter Waves in Medicine and
Biology": April, 1995 (Digest of papers) Moscow: IRE RAN,
pp 236-237 (in Russian).
Shub GM,
Luniova IO, Denisova SG, Ostrovskii NV (1995): Effects of
millimeter waves on bacteria in in vitro and in vivo
experiments. Moscow, Russia: 10th Russian Symposium
"Millimeter Waves in Medicine and Biology," April,
1995 (Digest of papers). Moscow: IRE RAN, pp 96-97 (in
Russian).
Smirnov AIu,
Zinovev SV, Bogoliubov VM (1991): An experimental study of the
action of weak-intensity superhigh-frequency electromagnetic
radiation in the millimeter range on metastasis of malignant
neoplasms. Vopr Kurortol Fizioter Lech Fiz Kult 4: 23-27 (in
Russian).
Tambiev AH,
Kirikova NN (1992): Perspectives on the application of
millimeter-range electromagnetic radiation in
photobiotechnology. Millimetrovie Volni v Biologii i Meditcine
1:48-54 (in Russian).
Tambiev AKh,
Kirikova NN, Lapshin OM, Betzkii OV, Novskova TA, Nechaev VM,
Petrov IYu. (1989): The combined effect of exposure to EMF of
millimeter and centimeter wavelength ranges on productivity of
microalgae. In Devyatkov ND (ed): "Millimeter Waves in
Medicine and Biology." Moscow: Radioelectronica, pp
183-188 (in Russian).
Temur'iants
NA, Chuyan EN (1992): Effect of nonthermal microwaves on
hypokinetic stress development in rats with different
individual features. Millimetrovie Volni v Biologii i
Meditcine 1:22-32 (in Russian).
Temur'iants
NA, Chuyan EN, Khomiakova OV, Tishkina OO (1994): Dependence
of the stress-protective effect of extremely-high-frequency
electromagnetic radiation on parameters of irradiation.
Millimetrovie Volni v Biologii i Meditcine 3:11-15 (in
Russian).
Temur'iants
NA, Chuyan EN, Tumaniants EN, Tishna OO, Victorov NV (1993):
Dependence of anti-stress effects of millimeter-range
electromangetic fields on localization of the exposed area in
rats with different typological features. Millimetrovie Volni
v Biologii i Meditcine 2:51-59 (in Russian).
Tsutsaeva AA,
Makarenko BI, Beznosenko BI, Gomosov VI, Simonova NYa,
Kovalenko LA, Shatilova LE, Tupchienko GS, Nikitash AV,
Kudokotseva OV, Rozniak AI, Lisenko NA, Shurda GG (1995):
Radioprotective effect of microwave action. Millimeter Waves
in Medicine and Biology, Digest of papers of the 10th Russian
Symposium with International Participation, 24-26 April,
Moscow, Russia, pp 123-124 (in Russian).
Zavizion VA,
Kudriashova VA, Khurgin YuI (1994): Effect of alpha-amino
acids on the interaction of millimeter-wave radiation with
water. Millimetrovie Volni v Biologii i Meditcine 3:46-52 (in
Russian).
Zemskov VS,
Korpan NN, Khokhlich IaI, Pavlenko VA, Nazarenko LS,
Koval'chuk AI, Stefanishin IaI (1988): Effect of
millimeter-band low intensity electromagnetic radiation on the
course of wound healing. Klin Khir 1:31-33 (in Russian).
Footnotes
1
EMF Database is produced by Information Ventures, Inc.
(Philadelphia, PA) and covers topics related to biological
effects of electromagnetic fields, from DC to submillimeter
wavelengths. The Database contains over 20,000 citations of
relevant publications from various sources, including
peer-reviewed journals, books, proceedings, and meeting
abstracts. Available citations are assimilated in the Database
without any pre-selection based on the language, affiliation of
the authors, or relevance to a particular EMF frequency range.
TABLE 1. Other
in vitro effects of millimeter wave radiation
Citation
|
Endpoints
/ Findings
|
Exposure
conditions
|
Details
|
1
|
2
|
3
|
4
|
Berzhanskaya
et al., 1995 |
Suppression
of bioluminescence of Photobacterium leiognathi |
36.2
to 55.9 GHz
1.3 to 48.0 m W/cm2
MMW heating < 0.1 oC |
The
effect reached maximum within 10 min, with a gradual
recovery after the cessation of exposure, and could be
repeated many times in the same cell culture. The
maximum effect (16-18% decrease) was caused by the lower
frequencies. At 36.2 GHz, 1.3 and 13 m W/cm2 intensities
produced virtually the same effect. |
Mudrick
et al., 1995 |
Changes
in the intensity of BaSO4-induced flash of
chemoluminescence in the presence of luminol in human
leukocytes |
42.19,
46.84, or 53.53 GHz
1 mW/cm2
30 min |
The
effect depended on the frequency, and the dependence was
individual for blood samples from each particular donor.
The maximum observed effect was a twofold flash
enhancement (p<0.01) at 42.19 GHz. |
Gapeev
et al., 1996 |
Inhibition
of the luminol-dependent chemoluminescence of
neutrophils activated by opsonized zymosan |
41.8
to 42.05 GHz
0.15-0.25 mW/cm2 |
In
the near zone of the irradiator, the effect depended on
the radiation frequency in a quasi-resonance manner,
while in the far field it was independent of the
frequency. |
Logani
and Ziskin, 1996 |
No
MMW effect on lipid peroxidation in phosphatidylcholine
liposomes |
53.6,
61.2, or 78.2 GHz
10, 1, and 500 mW/cm2, respectively, 30 or 60
min |
MMW
did not increase the level of lipid peroxidation under
any of the experimental conditions (in liposomes loaded
or not loaded with melanin, or in the presence or
absence of iron (III) adenosine diphosphate). |
TABLE 1.
(continued)
1
|
2
|
3
|
4
|
Roshchupkin
et al., 1994, 1996 |
MMW
changed aggregation of thymocytes with erythrocytes in a
dose- and frequency-dependent manner |
46.12
or 46.19 GHz
either:
(1) at 0.35 mW/cm2,
0 to 120 min,
or:
(2) 0.05 to 0.5 mW/cm2,
90 min
|
(1)
The threshold was 60 min for both frequencies,
increasing the number of aggregates to 115-140% of the
parallel control. The effect of 46.12 GHz did not change
when the exposure duration was further increased to 90
or 120 min, while the effect of 46.19 GHz fell to
80-90%. (2) The threshold was 0.25-0.35 mW/cm2.
The effect of 46.19 GHz stayed at 110-120% at 0.35 and
0.5 mW/cm2, while the effect of 46.12 GHz grew linearly
to 170% at 0.5 mW/cm2 |
Shub
et al., 1995 |
Changes
in transmissivity of R-plasmids in various strains of E.
coli and S. aureus |
6.0-6.7
mm band,
< 1 mW/cm2
30 min |
A
number of biologically-active frequencies affected the
transmissivity of R-plasmids, either decreasing or
increasing plasmid- and chromosome-dependent resistivity
to antibiotics Irradiation for 60 min had a
bacteriostatic effect, which was not related to the
activity of the recA-dependent DNA repair. Cells
carrying Ia , Ij, N, and E plasmids appeared to be
protected from the antibacterial effect of MMW. |
Kazbekov
and Vyacheslavov, 1987 |
No
nonthermal effects in prototrophic, thymidine-deficient,
and tryptophan-requiring strains of E. coli and B.
subtilis |
6-
to 7.8-mm wavelengths
5 mW/cm2 |
MMW
either had no effect on studied parameters (thymine and
thymidine uptake, potassium leakage, hydrogen ion
release, uptake of DNA, etc.), or produced the same
changes as conventional heating by 1-2 oC. |
Figure 1.
Absolute numbers and percentages of publications on topics
related to biological action of millimeter waves versus years of
publication.
The graph is
based on counts of citations in the EMF Database v. 3.0, 1997.
Studies by the former Soviet Union (FSU) scientists and by all
others (non-FSU) were counted separately. Vertical scale is the
number of published MMW studies per 2-year time intervals
(abscissa). Numbers next to the datapoints indicate the weight
(%) of MMW studies in the FSU and non-FSU bioelectromagnetic
research (i.e., the percentage of MMW studies relative to the
total number of studies included in the EMF database for the
respective time periods)

|