A pooled analysis of magnetic fields, wire codes, and childhood leukemia. Childhood Leukemia-EMF Study Group.

We obtained original individual data from 15 studies of magnetic fields or wire codes and childhood leukemia, and we estimated magnetic field exposure for subjects with sufficient data to do so. Summary estimates from 12 studies that supplied magnetic field measures exhibited little or no association of magnetic fields with leukemia when comparing 0.1-0.2 and 0.2-0.3 microtesla (microT) categories with the 0-0.1 microT category, but the Mantel-Haenszel summary odds ratio comparing >0.3 microT to 0-0.1 microT was 1.7 (95% confidence limits = 1.2, 2.3). Similar results were obtained using covariate adjustment and spline regression. The study-specific relations appeared consistent despite the numerous methodologic differences among the studies. The association of wire codes with leukemia varied considerably across studies, with odds ratio estimates for very high current vs low current configurations ranging from 0.7 to 3.0 (homogeneity P = 0.005). Based on a survey of household magnetic fields, an estimate of the U.S. population attributable fraction of childhood leukemia associated with residential exposure is 3% (95% confidence limits = -2%, 8%). Our results contradict the idea that the magnetic field association with leukemia is less consistent than the wire code association with leukemia, although analysis of the four studies with both measures indicates that the wire code association is not explained by measured fields. The results also suggest that appreciable magnetic field effects, if any, may be concentrated among relatively high and uncommon exposures, and that studies of highly exposed populations would be needed to clarify the relation of magnetic fields to childhood leukemia.

Biological, physical, and electrical parameters for in vitro studies with ELF magnetic and electric fields: a primer.

This paper presents material which is intended to assist researchers in identifying and controlling a range of biological, electrical, and other physical parameters that can affect the outcome of in vitro studies with extremely low frequency (ELF) magnetic and electric fields. Brief descriptions of power line magnetic and electric fields are provided and methods for the generation of 60 Hz as well as other ELF fields in the laboratory are surveyed. Methods for calculating and measuring exposure parameters in culture medium are also described. Relating in vitro and internal in vivo exposure conditions across different animal species is discussed to aid researchers in selecting levels of field exposure. The text is purposely elementary, and sometimes brief, with references provided to aid the interested reader in obtaining a fuller understanding of the many topics. Because the range of experimental parameters that can influence the outcome of in vitro studies with ELF fields is so broad, a multidisciplinary approach is normally required to carry out the research.

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.

An integrated ELF magnetic-field generator and incubator for long-term in vitro studies.

Long-term studies of the effects of low-frequency magnetic fields on cells in culture require an incubator that is free of contaminating magnetic fields and that provides automatic control of exposure duration, uniform applied fields, a uniform and well-controlled environmental temperature, and high reliability of the total system. We describe a dual-incubator system in which the enclosed solenoid of either unit can provide a sham exposure while the other generates a magnetic induction of up to 500 microT. Each solenoid-incubator unit contains an enclosed rack that can hold as many as 140 petri dishes for culturing cells; each unit is heated radiantly by circulating warm water. Field-exposure conditions and temperatures are continuously monitored and controlled by a microcomputer.

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.

Suppression of T-lymphocyte cytotoxicity following exposure to 60-Hz sinusoidal electric fields.

A significant 25% inhibition (P less than .005) of allogeneic cytotoxicity of the target cell MPC-11 by the murine cytotoxic T-lymphocyte line CTLL-1 was observed when the 4-h cytotoxicity assay was conducted immediately following a 48-h pre-exposure of the effector lymphocytes to a 10-mV/cm (rms) 60-Hz sinusoidal electric field. At 1.0 mV/cm a significant 19% inhibition (P less than .0005) was seen. At 0.1 mV/cm a nonsignificant 7% inhibition of cytotoxicity was noted. When the 4-h cytotoxicity assay was conducted in the presence of the field using previously unexposed effector lymphocytes, cytotoxicity was not significantly reduced. Cell proliferation in the presence of interleukin-2 was unaffected by the field. These data suggest a dose response and threshold (between 0.1 and 1.0 mV/cm) for inhibition of cytotoxicity in clonal T-lymphocytes by exposure to a 60-Hz sinusoidal electric field. These results suggest mechanisms by which 60-Hz electric fields could affect the function of cells of the immune system.

Long-term effects of sinusoidal extracellular electric fields in penicillin-treated rat hippocampal slices.

Rat hippocampal slices in 0, 0.25, 1.5 or 3 mM penicillin were exposed briefly to extracellular sinusoidal electric fields (20 s, 5 and 60 Hz, 20-40 mV/cm in tissue). Fields induced long-term (min) changes in population spike amplitudes in the CA1 cell layer. Post-field effects included both depression of strongly epileptiform responses and potentiation of weakly epileptiform and normal responses. Endogenous extracellular fields may participate in the dynamic regulation of the course of seizures.

Comparison between the effects of extracellular direct and sinusoidal currents on excitability in hippocampal slices.

The amplitude of population spikes in the CA1 cell layer of rat hippocampal slices was transiently altered during stimulation of the tissue with DC and sinusoidal extracellular electric fields parallel to the dendrosomatic axis of the CA1 pyramidal neurons. Field threshold was about 50 mV/cm in the tissue. Independently, long-lasting (min) increases in population spike amplitude followed sinusoidal fields as low as 7 mV/cm parallel or perpendicular to the cell axis.

Influences of sinusoidal electric fields on excitability in the rat hippocampal slice.

The influence of extracellular sinusoidal electric fields on the amplitude of population spikes evoked by single test pulses in excitatory pathways to CA1 pyramidal neurons was studied in rat hippocampal slices. The fields in the tissue were of the order of EEG gradients. Stimulation at 5 Hz, a frequency representative of hippocampal theta activity, was compared with 60 Hz, which is often used in kindling procedures. Brief stimulation (5-30 s) with both 5 and 60 Hz fields (20-70 mV/cmp-p in the perfusing solution) often produced a long-term increase (longer than 10 min) of the population spike. Fields at 60 Hz, but not at 5 Hz, also induced short-term depression (1-6 min) or transient post-field excitation (15-30 s). Prolonged stimulation (3 min) emphasized this frequency dependent response: fields at 5 Hz induced long-lasting potentiation while fields at 60 Hz always resulted in progressive depression persisting for a few minutes after the end of stimulation. These effects appeared as a global response of CA1 neurons. Antidromic responses studied during blockade of synaptic transmission (0.2 mM Ca2+, 4 mM Mg2+) were depressed during and following 3 min field stimulation at either frequency, which could reflect failing calcium mechanisms in the tissue. The field influence on the potential evoked by synaptic or antidromic stimulation was independent of the phase of the sine wave at which the test pulse was delivered, arguing against a direct polarization of the cell membrane by the fields. The experimental evidence suggests a functional role for EEG-like fields in hippocampal excitability.