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Biomedical subjects

W R Adey

Publications and source records attributed to W R Adey.

At least 19 recordsLinked to original sources
PubMed1997

Exposure of nerve growth factor-treated PC12 rat pheochromocytoma cells to a modulated radiofrequency field at 836.55 MHz: effects on c-jun and c-fos expression.

Rat PC12 pheochromocytoma cells have been treated with nerve growth factor and then exposed to athermal levels of a packet-modulated radiofrequency field at 836.55 MHz. This signal was produced by a prototype time-domain multiple-access (TDMA) transmitter that conforms to the North American digital cellular telephone standard. Three slot average power densities were used: 0.09, 0.9, and 9 mW/cm2. Exposures were for 20, 40, and 60 min and included an intermittent exposure regimen (20 min on/20 min off), resulting in total incubation times of 20, 60, and 100 min, respectively. Concurrent controls were sham exposed. After extracting total cellular RNA, Northern blot analysis was used to assess the expression of the immediate early genes, c-fos and c-jun, in all cell populations. No change in c-fos transcript levels were detected after 20 min exposure at each field intensity (20 min was the only time period at which c-fos message could be detected consistently). Transcript levels for c-jun were altered only after 20 min exposure to 9 mW/cm2 (average 38% decrease).

Adrenal Gland Neoplasms↗
PubMed1997

DNA synthesis and cell proliferation in C6 glioma and primary glial cells exposed to a 836.55 MHz modulated radiofrequency field.

We have tested the hypothesis that modulated radiofrequency (RF) fields may act as a tumor-promoting agent by altering DNA synthesis, leading to increased cell proliferation. In vitro tissue cultures of transformed and normal rat glial cells were exposed to an 836.55 MHz, packet-modulated RF field at three power densities: 0.09, 0.9, and 9 mW/cm2, resulting in specific absorption rates (SARs) ranging from 0.15 to 59 muW/g. TEM-mode transmission-line cells were powered by a prototype time-domain multiple-access (TDMA) transmitter that conforms to the North American digital cellular telephone standard. One sham and one energized TEM cell were placed in standard incubators maintained at 37 degrees C and 5% CO2. DNA synthesis experiments at 0.59-59 muW/g SAR were performed on log-phase and serum-starved semiquiescent cultures after 24 h exposure. Cell growth at 0.15-15 muW/g SAR was determined by cell counts of log-phase cultures on days 0, 1, 5, 7, 9, 12, and 14 of a 2 week protocol. Results from the DNA synthesis assays differed for the two cell types. Sham-exposed and RF-exposed cultures of primary rat glial cells showed no significant differences for either log-phase or serum-starved condition. C6 glioma cells exposed to RF at 5.9 muW/g SAR (0.9 mW/cm2) exhibited small (20-40%) significant increases in 38% of [3H]thymidine incorporation experiments. Growth curves of sham and RF-exposed cultures showed no differences in either normal or transformed glial cells at any of the power densities tested. Cell doubling times of C6 glioma cells [sham (21.9 +/- 1.4 h) vs. field (22.7 +/- 3.2 h)] also demonstrated no significant differences that could be attributed to altered DNA synthesis rates. Under these conditions, this modulated RF field did not increase cell proliferation of normal or transformed cultures of glial origin.

Animals↗
PubMed1997

Focus formation of C3H/10T1/2 cells and exposure to a 836.55 MHz modulated radiofrequency field.

Disruption of communication between transformed cells and normal cells is involved in tumor promotion. We have tested the hypothesis that exposures to radiofrequency (RF) fields using a form of digital modulation (TDMA) and a chemical tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), are copromoters that enhance focus formation of transformed cells in coculture with parental C3H/10T1/2 murine fibroblasts. RF field exposures did not influence TPA's dose-dependent promotion of focus formation in coculture. Cell cultures were exposed to an 836.55 MHz TDMA-modulated field in TEM transmission line chambers, with incident energies that simulated field intensities at a user's head. Specific absorption rates (SARs) of 0.15, 1.5, and 15 muW/g were used during each digital packet, and the packet frequency was 50/s. The TEM chambers were placed in a commercial incubator at 37 degrees C and 95% humidity/5% CO2. The RF field exposures were in a repeating cycle, 20 min on, 20 min off, 24 h/day for 28 days. At 1.5 muW/g, TPA-induced focus formation (at 10, 30, and 50 ng/ml) was not significantly different in RF-exposed cultures compared to parallel sham-exposed cultures in ten independent experiments in terms of the number, density, and area of foci. Similarly, at 0.15 and 15.0 muW/g, in two and four experiments, respectively, RF exposure did not alter TPA-induced focus formation. The findings support a conclusion that repeated exposures to this RF field do not influence tumor promotion in vitro, based on the RF field's inability to enhance TPA-induced focus formation.

Analysis of Variance↗
PubMed1996

Extremely-low-frequency magnetic fields disrupt rhythmic slow activity in rat hippocampal slices.

Several studies have indicated that weak, extremely-low-frequency (ELF; 1-100 Hz) magnetic fields affect brain electrical activity and memory processes in man and laboratory animals. Our studies sought to determine whether ELF magnetic fields could couple directly with brain tissue and affect neuronal activity in vitro. We used rat hippocampal slices to study field effects on a specific brain activity known as rhythmic slow activity (RSA), or theta rhythm, which occurs in 7-15 s bursts in the hippocampus during memory functions. RSA, which, in vivo, is a cholinergic activity, is induced in hippocampal slices by perfusion of the tissue with carbachol, a stable analog of acetylcholine. We previously demonstrated that the free radical nitric oxide (NO), synthesized in carbachol-treated hippocampal slices, lengthened and destabilized the intervals between successive RSA episodes. Here, we investigate the possibility that sinusoidal ELF magnetic fields could trigger the NO-dependent perturbation of the rate of occurrence of the RSA episodes. Carbachol-treated slices were exposed for 10 min epochs to 1 or 60 Hz magnetic fields with field intensities of 5.6, 56, or 560 microT (rms), or they were sham exposed. All exposures took place in the presence of an ambient DC field of 45 microT, with an angle of -66 degrees from the horizontal plane. Sinusoidal 1 Hz fields at 56 and 560 microT, but not at 5.6 microT, triggered the irreversible destabilization of RSA intervals. Fields at 60 Hz resulted in similar, but not statistically significant, trends. Fields had no effects on RSA when NO synthesis was pharmacologically inhibited. However, field effects could take place when extracellular NO, diffusing from its cell of origin to the extracellular space,was chelated by hemoglobin. These results suggest that ELF magnetic fields exert a strong influence on NO systems in the brain; therefore, they could modulate the functional state of a variety of neuronal ensembles.

Animals↗
PubMed1996

Mechanical vibration in "double-wound" magnetic field exposure coils.

It has been suggested that "double-wound" (bifilar) exposure coils are capable of producing a sham environment in which hum and vibration will be "similar" to the field-exposed condition. We found by direct measurements in a bifilar coil system that vibration amplitude in sham and exposed conditions differed by a factor of 50 when our test system was driven at B = 10 mT. We also found that the normal laboratory environment can include vibrations of an intensity similar to that produced by the exposure system, although not necessarily of similar spectral distribution.

Acceleration↗
PubMed1995

Exposure of Drosophila melanogaster embryonic cell cultures to 60-Hz sinusoidal magnetic fields: assessment of potential teratogenic effects.

There is considerable concern about potential detrimental health effects associated with exposure to environmentally relevant magnetic fields. One specific concern relates to potential effects of magnetic field (MF) exposure on reproduction and development. Consequently, an in vitro teratogenesis (developmental toxicity) assay employing embryonic Drosophila cells has been used to determine whether exposure to a 60-Hz MF of 100 microT for 16-18 hr is itself teratogenic and whether such an exposure could potentiate the teratogenic response induced by a chemical teratogen (developmental toxicant). The results demonstrated that (1) MF exposure alone did not induce a teratogenic response, whether the MF was oriented parallel or perpendicular to the plane of the culture dishes; and (2) MF exposure did not alter the teratogenic response induced by optimal or suboptimal concentrations of three chemical teratogens (retinoic acid, hydroxyurea, and cadmium). Furthermore, in additional studies, Drosophila embryos were exposed to 60-Hz MFs of 10 and 100 microT for 24 hr or for their entire development time (i.e., until adult ecolsion, about 10 days). Results demonstrated that MF exposure did not produce an increase in developmental abnormalities over those observed in unexposed controls.

Animals↗
PubMed1994

Nitric oxide modulates rhythmic slow activity in rat hippocampal slices.

We investigated the role of nitric oxide (NO) in controlling the rate of occurrence of muscarinic rhythmic slow activity (RSA) episodes induced by carbachol in rat hippocampal slices. Typically, a series of several short intervals (< 40 s) between RSA episodes alternated with one or two longer intervals. Treatments with inhibitors of NO synthesis (NG-nitro- or NG-methyl-L-arginine) or with hemoglobin shortened and stabilized all intervals. By contrast, applications of an NO donor (sodium nitroprusside) or membrane permeant cGMP analogs (8-bromo-cGMP or dibutyryl-cGMP) during blockade of NO synthesis lengthened and destabilized the intervals. The importance of cholinergic mechanisms in learning and memory is well known and our findings suggest that NO could influence synaptic plasticity by modulating the occurrence of a muscarinic component of hippocampal RSA.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1993

The effect of moving air on detection of a 60-Hz electric field.

Two potential mechanisms in detection of a 60-Hz electric field by albino rats were examined: field-induced movement of the vibrissae and field-induced vibration of the skin. Specifically, the experiment tested field detection in a moving stream of air designed to mask field-induced movement of the skin, fur, and vibrissae. Rats were trained to detect electric fields and were then tested at field intensities from 0-25 kV/m rms. As previously reported, rats demonstrate unmistakable behavioral evidence of field detection at all intensities above 7.5 kV/m. After establishing detection in still air, field detection was re-examined in moving air (average air velocity approximately 2.8-6.8 m/s). The primary result is that the wind produced no change in detection at field intensities above threshold (> 7.5 kV/m). Indeed, at these intensities detection was virtually identical in still and moving air. A secondary finding is that moving air produced statistically significant (P < .05) but apparently contradictory effects on detection when the field intensity was below threshold. On no-field trials the wind lowered scores (i.e., fewer presses on the field-off lever); however, on subthreshold field trials, the wind actually increased detection scores (i.e., more presses on the field-on lever). While this no-field and subthreshold field result is interesting and deserves further study, we place primary emphasis on the finding that, if the field was detectable in still air, it was also detectable in moving air. This result leads us to believe that movement of the vibrissae, fur, or skin is not likely to be the main mechanism of electric-field detection in our subjects.

Air Movements↗
PubMed1993

Biological effects of electromagnetic fields.

Life on earth has evolved in a sea of natural electromagnetic (EM) fields. Over the past century, this natural environment has sharply changed with introduction of a vast and growing spectrum of man-made EM fields. From models based on equilibrium thermodynamics and thermal effects, these fields were initially considered too weak to interact with biomolecular systems, and thus incapable of influencing physiological functions. Laboratory studies have tested a spectrum of EM fields for bioeffects at cell and molecular levels, focusing on exposures at athermal levels. A clear emergent conclusion is that many observed interactions are not based on tissue heating. Modulation of cell surface chemical events by weak EM fields indicates a major amplification of initial weak triggers associated with binding of hormones, antibodies, and neurotransmitters to their specific binding sites. Calcium ions play a key role in this amplification. These studies support new concepts of communication between cells across the barriers of cell membranes; and point with increasing certainty to an essential physical organization in living matter, at a far finer level than the structural and functional image defined in the chemistry of molecules. New collaborations between physical and biological scientists define common goals, seeking solutions to the physical nature of matter through a strong focus on biological matter. The evidence indicates mediation by highly nonlinear, nonequilibrium processes at critical steps in signal coupling across cell membranes. There is increasing evidence that these events relate to quantum states and resonant responses in biomolecular systems, and not to equilibrium thermodynamics associated with thermal energy exchanges and tissue heating.

Animals↗
PubMed1993

Roles of the NMDA and quisqualate/kainate receptors in the induction and expression of kindled bursts in rat hippocampal slices.

We used combinations of NMDA and quisqualate/kainate (Q/K) receptor antagonists and low Mg2+ (0.1 mM) solutions to study the respective roles of these receptors during in vitro kindling of interictal bursts in the CA3 area of rat hippocampal slices. Intracellular and extracellular recordings in CA3 showed that Q/K receptors were not necessary for the induction of kindling once the Mg2+ block of NMDA was alleviated, but that the expression of bursts kindled via NMDA-driven mechanisms was Q/K-dependent.

Animals↗
PubMed1993

60 Hz magnetic field acts as co-promoter in focus formation of C3H/10T1/2 cells.

Disruption of communication between transformed cells and normal cells is involved in tumor promotion. We have tested the hypothesis that 60 Hz electromagnetic (EM) field exposures and a chemical tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) are co-promoters that enhance focus formation of transformed cells in co-culture with normal cells. EM field exposures alone did not affect the growth curves of parental C3H/10T1/2 fibroblasts or daughter mutant cells, UV-TDTx10e. Furthermore, EM field exposures alone did not promote focus formation of mutant cells in co-culture with parental cells under the conditions tested. However, EM field exposures co-promoted with TPA by increasing focus formation in co-culture. Cell cultures were exposed to an EM field in custom-built solenoidal incubators. The field exposures were 1.0 Gauss in a schedule of 1 h epochs four times daily for 28 days. Video image analysis of three independent experiments showed that field-exposed cultures produced 1.9-fold more foci than sham-exposed cultures when treated with TPA. The total area of foci per dish increased 2.2-fold and the number of cells in stained foci increased 2.3-fold. In a TPA dose-response, focus formation began at 3 ng/ml with no difference between field-exposed and sham-exposed co-cultures. However, at the TPA concentrations of 10, 20, 40, 50 and 100 ng/ml EM field exposures enhanced focus formation by an average of 150%. This study suggests that chronic intermittent exposures to a 60 Hz EM field and a chemical tumor promoter influenced membrane-related events by co-promoting focus formation.

Animals↗
PubMed1993

Effect of 72 Hz pulsed magnetic field exposure on ras p21 expression in CCRF-CEM cells.

CCRF-CEM T-lymphoblastoid cells have been exposed to an asymmetric electromagnetic signal pulsed at 72 Hz for up to 28 hr. Following exposure, cells were lysed and extracted, and the extract was electrophoresed on SDS-polyacrylamide gels. Proteins were electroblotted onto nitrocellulose membranes and the product of the ras proto-oncogenes, p21, was identified and quantitated by successive treatment with pan ras p21 antibody, second antibody-alkaline phosphatase conjugate, and enzyme substrate. No changes in p21 levels were observed for the first 6 h of electromagnetic field exposure as compared to unexposed control cells. However, from 6-16 h exposure, p21 levels in exposed cells decreased linearly to only 30% of control values. From 16-28 h exposure, p21 levels in exposed cells increased nearly linearly to control cell values. Slot-blot analysis indicated that altered p21 protein expression is a result, at least in part, of changes in the levels of N-ras mRNA. No concomitant changes were detected in either cyclic AMP levels or in the expression of cell surface markers. While the significance of the marked reduction in cellular p21 is unclear, it does not appear to be related to cell differentiation.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1992

Magnetic field-induced changes in specific gene transcription.

Magnetic fields are physical, environmental agents that have been shown to produce a variety of responses in cellular and animal studies, including general changes in gene transcription. In this study, the nuclear run-off assay has been employed to assess alterations in specific gene transcription in CEM-CM3 T-lymphoblastoid cells exposed for 15-120 min to a 1 gauss sinusoidal magnetic field at 60 Hz. Time-dependent and cell density-dependent changes in the transcription of c-fos, c-jun, c-myc and protein kinase C (beta-form) have been observed and quantitated. Additionally, changes in transcript levels, assessed by slot-blot analysis, have been found to parallel the changes in gene transcription. These data suggest an important role for magnetic field exposure in altering cellular processes.

Cell Line↗
PubMed1991

Calcium uptake by leukemic and normal T-lymphocytes exposed to low frequency magnetic fields.

Calcium-ion uptake by normal and leukemia lymphocytes increased during a 30-min exposure to a 13.6 Hz, sinusoidal magnetic field at 20 microT peak. The time-varying field was horizontal and parallel to a 16.5 microT component of the ambient static magnetic field. The uptake of 45Ca2+ increased 102% in a line of murine, cytotoxic T-lymphocytes (C57B1/6-derived CTLL-1), increased 126% in freshly-isolated spleen lymphocytes (C57B1/6 mice), and increased 75% in a line of lymphoma cells (C57B1/6-derived EL4). In contrast, there was no effect when the same field was applied for 30 min immediately before--as opposed to during--incorporation of calcium ions. When spleen lymphocytes were exposed during incubation with 45Ca2+ to a 60 Hz magnetic field at 20 microT peak, a small but statistically significant increase (37%) in uptake of the labeled ions occurred. These results indicate that weak, alternating magnetic fields might affect calcium-dependent functions of normal and leukemic lymphocytes.

Animals↗
PubMed1991

Transition from normal to epileptiform activity in kindled rat hippocampal slices.

We previously demonstrated kindling of synchronized bursts (ISs) by repeated sine-wave stimulation (SW: 2-5 sec, 60 Hz, 20-50 microA, every 5 min) in the CA2/3 area of rat hippocampal slices. Here we report the behavior of individual CA2/3 neurons during the kindling procedure. Intra- and extracellular recordings were obtained concurrently before, during and following SW. Test pulses and SWs were applied in CA2/3 or CA1 stratum radiatum. Neuronal response to to intracellular stimulation was tested by 100 msec depolarizing dc pulses or by 2-20 sec sinusoidal currents. The role of the N-methyl-D-aspartate (NMDA) receptor in the transition from normal responses to ISs was assessed by perfusing the slices with a specific antogonist (DL-2-amino-5-phosphono-valeric acid, APV, 50-200 microM). Our results show that kindling of ISs occurred in two steps: (1) via NMDA-dependent depolarizations during SW, or during SW-induced afterdischarges, and (2) through the recruitment of secondary, late EPSPs (1EPSPs), between consecutive SWs. ISs developed from the 1EPSPs, while the early responses (action potentials, EPSPs, and population spikes) remained unchanged. Kindling of ISs occurred with no changes in resting membrane potential, membrane resistance, or threshold of action potentials. APV did not block kindled ISs, but considerably reduced their amplitude and duration, and increased their frequency. These latter findings suggest that APV-insensitive mechanisms, activated through NMDA-dependent processes, were responsible for the triggering of ISs, and that NMDA receptor systems participated in the control of their rate of occurrence.

2-Amino-5-phosphonovalerate↗
PubMed1990

Prenatal exposure to a low-frequency electromagnetic field demasculinizes adult scent marking behavior and increases accessory sex organ weights in rats.

Pregnant Sprague-Dawley dams were exposed to a low-level, low-frequency pulsed electromagnetic (EM) field (15 Hz, 0.3 msec duration, peak intensity 8 gauss) for 15 min twice a day from day 15 through day 20 of gestation, a period in development that is critical for sexual differentiation of the male rat brain. No differences in litter size, number of stillborns, or body weight were observed in offspring from field-exposed dams. At 120 days of age, field-exposed male offspring exhibited significantly less scent marking behavior than controls. Accessory sex organ weights, including epididymis, seminal vesicles, and prostate, were significantly higher in field-exposed subjects at this age. However, circulating levels of testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as epididymal sperm counts, were normal. These data indicate that brief, intermittent exposure to low-frequency EM fields during the critical prenatal period for neurobehavioral sex differentiation can demasculinize male scent marking behavior and increase accessory sex organ weights in adulthood.

Analysis of Variance↗