Intermediary Metabolism
Metabolic indices of carbohydrate metabolism are sensitive to EMFs (1-6). Dumanskiy and Tomashevskaya (1) exposed rats to 2.4 GHz (2 hr./day), for up to 4 months. At 100 and 1000 µW/cm2 the animals exhibited a series of biochemical alterations in liver tissue that included a decline in cytochrome oxidase activity, an increase in glucose-6-phosphate dehydrogenase activity, and an activation of mixed-function oxidases in the microsomal fraction of the tissue. The largest changes were seen after 1 month's irradiation, following which there was a tendency for the various enzyme levels to return to baseline. Enzyme activities were unaffected by exposure to 10 µW/cm2. In another study, Dumansky et al. reported an increase in blood glucose in humans following exposure to 15 kv/m 50 Hz, I.5 hours/day for 6 days (2).
Chernysheva and Kholodov studied the effect of a 90-gauss, 50 Hz magnetic field on several aspects of carbohydrate, protein, and nucleic acid metabolism in the rat (3). They found EMF-induced alterations in each area, including changes in liver glycogen, elimination of ammonia, glutamine content in the heart, and nucleic-acid levels in brain and liver (Table 8.1).
Table 8.1. METABOLIC PARAMETERS IN RATS (in mg%) EXPOSED FOR 6 MONTHS TO 90 GAUSS (3 hr/day)
In a study of muscle metabolism (4), lactate dehydrogenase activity in skeletal and cardiac muscle of rats was measured by disk electrophoresis. There was an increase in the enzyme's activity in both kinds of muscle 1-2 days after exposure to 200 gauss, 50 Hz, for 24 hours; histological changes indicative of glycolytic processes were also found. These observations were consistent with an earlier report of impaired functional activity of muscle following EMF exposure (5). After 1 month, rabbits exposed to 30-40 kv/m, 05 Hz, were unable to lift a weight as large as that lifted by the nonexposed rabbits.
The sensitivity of metabolic parameters to EMFs is underscored by studies that involve EMFs which have intensities comparable to typical environmental fields; the Mathewson et al. study (6) is a blood example. Rats were exposed for 28 days to 2, 10, 20, 50 and 100 v/m in three replicate experiments, following which complete blood chemistries were performed; the serum glucose levels are listed in table 8.2A. Although some differences between the control and exposed groups were seen, no trend or dose-effect relationship was manifested and consequently, the authors regarded the data as having failed to show a biological effect of the EMF (6). But the 60-Hz electric field in the test cages was 0.18-9.15 v/m, depending on the particular test cage location (8). As a consequence, the 4 5 -Hz, 2v/m group is more properly viewed as a control group in relation to the 50-100 v/m exposed groups. When we did this, the Mathewson data revealed significant increases in serum glucose in each replicate (Table 8.2B). (This approach to the Mathewson data also suggests the existence of effects on other parameters, including globulins, protolipids, and triglycerides.)
Table 8.2. AVERAGE GLUCOSE LEVELS IN THREE REPLICATE EXPERIMENTS
Cellular bioenergetics can be altered by EMFs (10-14): the changes seem to be adaptive in nature, and to depend on the exposure level and duration. A single 10-minute exposure at 25 µW/cm2, 10 GHz, produced a decrease in the phosphorylation effectiveness factor (ADP/O) in liver mitochondria, and an increase in respiratory control (RC) in kidney mitochondria (10). After ten such exposures, the oxygen consumption and RC were both increased in kidney mitochondria. A single exposure at 100 µW/cm2 caused a rise in oxygen consumption and an increase in ADP/O in liver mitochondria and a decrease in RC in kidney mitochondria (10). After ten such exposures, almost all the indices of oxidative phosphorylation in both mitochondria returned to normal, thereby suggesting that the enzyme systems had adapted to the EMF. A decrease in RC was also seen in guinea pig mitochondria exposed in vitro to 155 v/m, 60 Hz (11).
Rats were exposed to 10, 25, 50, 100, 500 and 1000 µW/cm2, at 2.4 GHz, as follows: 40 minutes per day, 3 times per day, 5 days per week, for 4 months (intended to simulate the exposure received from household microwave ovens) (12). It was found that the EMF altered respiration and phosphorylation in liver mitochondria; there was an increase of nonphosphorylating oxidation of metabolites of the Krebs cycle, and a decrease in the oxygen consumption rates during phosphorylating respiration. A decrease in oxygen consumption rate was also found after 20 days' exposure to 1000 µW/cm2, 46 GHz (13).
In a study of skeletal-muscle metabolism, rats were exposed to 300-900 gauss, 7 KHz for up to 6 months (1.5 hr./day) (14). Creatine phosphate and ATP levels decreased, and ADP levels increased following exposure. The changes were consistent with both an increased energy requirement, and an adverse effect on ATP formation. On the basis of in vitro studies of oxidative phosphorylation and oxygen consumption involving tissues from the exposed animals, the authors favored the latter possibility. Two consequences of the observed changes in cell bioenergetics involved carbohydrate and nitrogen metabolism. Decreased glycogen levels were found, indicating a compensatory glycogenolysis and, hence, an enhanced production of high-energy phosphate compounds. Secondly, EMF exposure produced an increase in tissue ammonia levels with no corresponding increase in glutamine synthesis. This may have been due to the ATP deficiency, although the influence of other factors involved in glutamine production-glutamic acid and manganese for example-could not be excluded.
Shandala and Nozracher (15) reported that kidney function and water-salt metabolism in rabbits (diuresis, chloride elimination, acid-base balance) were altered following the exposure to 50 and 500 µW/cm2, 2.4 GHz. In a comparable study (16), it was found that similar kinds of changes (urinary levels of potassium, sodium and nitrogen) were sex dependent; most of the metabolite levels were increased in females and decreased in males.
The altered nitrogen levels (16) suggested an EMF effect on protein synthesis. This was confirmed by Miro et al. (17) who found that 160 hours' exposure of mice to 2000 µW/cm2, 3 GHz, resulted in an increase in protein synthesis in the liver, thymus, and spleen as determined by cytohistological techniques.
The most important study to date on lipid metabolism was performed by Dietrich Beischer and his colleagues (18). Volunteers, confined for up to 7 days, were exposed to a 1-gauss magnetic field, 45 Hz, for 24 hours: they did not know which 24-hour period during their confinement would be chosen for the application of the EMF. It was found that the serum triglycerides in 9 of 10 exposed subjects reached a maximum value 1-2 days after EMF exposure (Fig. 8.1); similar trends were not seen in any of the control subjects (18). Measurement of respiratory quotients for basal conditions established that the hyperlipemia could not have been caused by a change in the proportion of fats and carbohydrates being oxidized. Also, previous work had shown that confinement alone had no effect on serum triglycerides. This suggested that the observed effect may have been due to a change in the activity of one or several of the enzymes involved in lipid homeostatis, perhaps triglyceride lipase. The 1-2 day latency suggested that the action of the EMF involved an enzyme precursor, not the enzyme itself (the EMF influence would then be felt only after existing enzyme stores had been depleted).
Fig. 8.1. Average serum triglyceride levels of exposed and control subjects.
There are several other studies involving low-frequency magnetic field. There are several other studies involving low-frequency magnetic field effects on fat metabolism (19, 20). Rabbits that were maintained on a high-cholesterol diet were exposed to the field for 5 weeks and then examined for serum lipid levels and aortic plaque formation (19). A reduction of both cholesterinemia and plaque formation was found in the exposed animals. A reduction in blood cholesterol (50 mg/ml on the average) was also reported in ten human subjects following local application of a magnetic field (20).
Vitamin B6 (pyridoxine) is involved in the nonoxidative degradation of amino acids, synthesis of unsaturated fats, and the hydrolysis of glycogen. Exposure of rats to 570 µW/cm2, 2 GHz, for 15 days (3 hr./day) led to a decrease in vitamin B6 levels in blood, brain, liver, kidney, and heart; the levels of the vitamin in skeletal muscle increased (21) (Table 8.3).
Table 8.3. EFFECT OF EMF ON VITAMIN B6 LEVELS IN RAT TISSUES
Trace levels of many metallic elements are found in body tissues; they are known to take part in enzyme activation, formation of proteins, redox reactions, and possibly in other biochemical processes. Both high- and low-frequency EMFs have been found capable of altering body trace-element distribution (22-24). Groups of 10 rats each were exposed to 2.4 GHz at 10, 100, and 1000 µW/cm2, 8 hours/day for 3 months. At the end of the exposure period, the animals were sacrificed and the levels of copper, manganese, nickel and molybdenum in the major organs were determined by optical spectroscopy. Changes in the level and distribution of all four elements were found (Table 8.4). The copper level decreased in both liver and kidney, possibly as a result of increased synthesis of ceruloplasmin-this would be consistent with the observed increase of copper in blood. There was, generally, an increase in copper in those organs that use the element in hemopoiesis and redox processes, possibly indicating a basic compensatory response to EMF radiation. The copper content of hard tissue was virtually unchanged by the field.
Table 8.4. TRACE ELEMENTS IN RAT TISSUES FOLLOWING EXPOSURE AT 2.4 GHz
In comparison to copper, manganese metabolism was less influenced by the EMF; it increased in most organs, and decreased in hard tissue.
Teeth and bone were the principal reservoirs for molybdenum, and they exhibited no change in molybdenum concentration except following exposure to the highest strength EMF. In contrast, the molybdenum levels in the soft tissues, which accounted for less than 10% of the total body molybdenum, were altered at even 10 µW/cm2.
The content of nickel in the various organs was influenced by each EMF intensity. It rose in some tissues, and fell in others; the heart, which exhibited a sixfold increase, was the most strongly affected tissue.
Trace element analysis has also been performed on rats exposed to low-frequency EMFs. Following exposure to 1, 2, 4, 7, and 15 kv/m, 50 Hz, for 4 months (2 hr./day), significant changes were found in the distributions of copper, molybdenum, and iron among the tissues, even at 1 kv/m, the lowest field strength employed (23) (Table 8.5). In subsequent studies by the same authors, similar changes were found after exposure to 7-15 kv/m for only 30 minutes/day (24).