Can Hertz be harmful? An endocrine action of extremely low frequency electromagnetic fields

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TIPS - December 1983 relapse in man and, as Del Soldato suggested, may assist in the search for drugs to treat IBD in man. Overall, the meeting was most useful in bringing together research workers and clinicians working in different disciplines to discuss diseases of the lower bowel, knowledge of which is still in its infancy. It

was certainly a good opportunity to have a spring-cleaning of thoughts. K D. RAINSFORD

Department of Pharmacology, University of Cambridge, Hills Road, Cambridge, UK.

Note The proceedings of the symposium have been published: New Trends in

the Pathophysiology and Therapy of the Large Bowel, edited by L. Barbara, M. Miglioli and S. F. Phillips, Elsevier, Amsterdam, 1983

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Current

awareness

series K e y d e v e l o p m e n t s in p h a r m a c o l o g y

processes that link the activation of ct,adrenoceptors to the final effects.

,-Adrenergic action: only calcium? The mechanism of signal transduction that follows ctl-adrenergic activation has remained obscure in spite of the efforts of many researchers, et~-Adrenoceptors seem to be linked to a caicium signailing-process which involves phosphatidylinositol turnoveP-3. A large amount of evidence supporting a role of calcium in oa-adrenergic action already exists. It has been observed that o.-adrenergic activation, as well as activation by other hormones and neurotransmitters) such as vasopressin, angiotensin I1 or muscarinic-cholinergic agonists) result in significant changes in the steady state concentration of free calcium in the different cell compartments; the data suggest that calcium may act as a second messenger or coupling factor (reviewed in Ref. 4). However, at least three groups have recently proposed that the process of signal transduction for c~l-adrenergic agents may involve factors besides calcium and that it may involve more than one pathway s-7. The evidence for this can be sammarized as shown below. (1) The metabolic effects of o,-adrenergic agents in liver cells, depend to a much lesser extent on the presence of extracellular calcium than those of vasopressin or angiotensin I1 (Ref. 8). (2) It has been reported that under conditions of calcium depletion, a~-adrenergic agents (but not vasopressin or angiotensin II) elevate cAMP levels7. (3) Insulin diminishes the activation of phosphorylase produced by ota-adrenergic amines but not the activation of this enzyme produced through the action of vasopressin 9. (4) In hepatocytes from hypothyroid animais the glycogenolytic action of vasopressin, angiotensin II or the calcium ionophore A23187 are nearly abolished, whereas

al-adrenergic activation results in clear stimulation of this metabolic pathwayS; these latter data indicate that a~-adrenergic activation can produce metabolic effects in cells which are insensitive to calciumsignalling. (5) The stimulation of secretion produced by al-adrenergic agents is markedly decreased in parotid cells from old rats as compared with that in cells from young animals; there was no significant change in the number of o.-adrenoceptors or in the response produced by cholinergic activation of the cells~. Thus, it is becoming clear that our present schemes for hormone action are incomplete and that the actions of a~-adrenergic amines are affected by the experimental conditions to an extent different from those of other agents (which supposedly act through the same mechanism). Further research is urgently required to clarify the

J. ADOLFO GARCfA-S,g.INZ AND SILVIA CORVERA

Departamento de Bioenerg~tica, Centro de lnvestigac~ones en Flslologfa Celular; Universidad Nacional Aut6noma de M~xtco. Apartado Postal 70-600 04510, Mdxico, DF.

Reading list 1 Michell, R. H. (1975) Biochim. Bzophys. Acta 415, 81-147 2 Jones, L. M. and Mmhell, R. H. 0978)Bzochem. Soc. Trans. 6, 673-688 3 Fain, J.N andGarcia-S/fin~,J A (1980)LlfeSo. 26, 1183-1194 4 Williamson, J R., Cooper, R. H. and Hack, J B. (1981) Bzoctum. Biophys. Acta 639, 243-295 5 Corvera, S and Garcia~S~nz. J A. (1983) FEBS Lett. 153, 366-368 6 Bodner, L.,Hoopes, M T.,Gee, M.,Ito, H.,Roth, G. S. and Baum, B. J (1983)J. Biol. Chem. 258, 2774-2777 7 Morgan, N G., Blackng)te, P. F. and Exton, J H. (1983)J. Biol. Chem. 258, 5103-5109 8 Corvera, S and Garcia-S/dnz, J. A. (1982) Life SCL 31,2493-2498 9 Dehaye, J. P, Hugh¢*, B P, Blackmore, P. F and Exton, J. H ( 1981 ) Biochem. J. 194,949-956

Can Hertz be harmful? An endocrine action of extremely low frequency electromagnetic fields In less than a century, a network of high voltage electrical distribution lines has been laid across the globe. Simultaneously, the world has been bathed in a sea of electromagnetic communications. Eskimos trudging the boreal snows, Bedouin gazing at the stars over Sinai and Americans relaxing in their homes of an evening need only to turn on a radio to be made aware of the electromagnetic ambience in which they live. Mankind is now continuously and intimately exposed to culturally produced electromagnetic fields.

The heaviest exposure to culturally produced fields derives from FM radio broadcasts which fail within the 30-300 mHz, or very high frequency (VHF) range. The distribution and utilization of electricity, however, is the major source of exposure to fields with frequencies in the 0-300 Hz, or extremely low frequency (ELF) range. At a frequency of 10 Hz, the solar flux on the earth does not exceed 1 mV m -1. In American homes, however, 60 Hz fields of 1-10 V m -1 are typically present. Fields may be as high as 250 V m -1 near electric blankets.

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TIPS - December 1983

490 Gradients under 60 Hz high voltage power lines reach 10 kV m -~ (Ref. 1). It is accepted, both in North America and the USSR, that exposure to fields in the microwave range (<1 GHz) can be harmful. Both nations have exposure standards, those of the USSR being by far the stricter. The USA permits continuous exposure to fields of no more than 1 mW cm 2, equivalent to a gradient of 61 V m ' in dry air. What about fields of lower frequency? Do ELF, non-ionizing electromagnetic fields have any biological effects? In view of the ubiquity of exposure, it is surprising that a question like this still lies on the periphery of respectable and fashionable research. Despite this, a considerable body of work has accumulated, much of it originating in the USSR. This intricately dense and inconsistent literature provides no clear answer to this question. It appears to an outsider that every report of a phenomenon is counteracted with a claim that the observation is an artifact, and a second report claiming an inability to repeat the findings of the first. Despite this, there are numerous reports, derived from many different systems, of biological phenomena associated with exposure to electromagnetic radiationL How are these reports to be interpreted? For in-vivo studies, are the observed responses behavioral or physiological? That is to say, are they a reaction to a perception of the field by the test animal rather than a true effect of the field? A recent report demonstrates a strong correlation between the incidence of suicide and the intensity of the electromagnetic field from overhead power lines at the domicile. Is this truly an effect of the electromagnetic field, or is it assodated with some other environmental alteration produced by the presence of the power line2? If it can be shown that the response to an electromagnetic field is a true physiological response, is this a response to the field per se or a response secondary to the thermal energy imparted by the electromagnetic field? Lymangrover et al. in a recent pape rs claimed to have demonstrated an endocrine effect of a 60 Hz electric field/n vitro, independent of a thermal effect. The frequency employed is important because this is the frequency used in power lines in the USA. Conventional wisdom seems to suggest that nonthermal biological effects of electromagnetic radiation are primarily seen in the CNS, and that peripheral actions are secondary to these. Such effects, for example, might result in an alteration in blood--brain transport, or in neuronal polarization. One reason for this belief is that the enhancement of an electrical gradient at the surface of the body is greatest at the head

for an erect human in an electromagnetic field. However, using a purely in-vitro preparation, Lymangrover et al. showed that a 60 Hz electromagnetic field applied to superfused adrenal cortical tissue will triple the production of corticosterone in response to ACTH. This demonstrates that such fields have direct effects on the steroidogenic responsiveness of rat adrenals. An important observation was that the rate of steroid production was a function not only of the frequency, but also of the field strength. At a field strength of 10 kV m -1, a 60 Hz field stimulated steroid production in response to ACTH. However, this effect was not seen at field strengths of 5, 100, or 1 000 kV m -1. In the jargon of this particular literature, there is an 'intensity window', in which a response is seen only at certain combinations of field strengths and frequencies. Similar 'windowed' responses had been previously seen in the release of calcium from chick cerebral hemispheres4,5. Calcium release from isolated cerebral tissues was decreased in electrical fields of 1-75 Hz, with corresponding electrical gradients of 5-100 V m-L The degree of inhibition was maximum at fields of 6-16 Hz and a gradient of 10 V m -x (Ref. 4). Thus, there was both a frequency and amplitude 'window' for the inhibitory action. ELF amplitude modulation of weak radio fields (147 mHz) applied to similar preparations, on the other hand, increased calcium effiux. The effect was maximal at modulation frequencies of 16 Hz, decreasing at both higher and lower modulation frequencies5. Thus, within the same preparation, depend-

ing on the frequencies and amplitudes involved, increases, decreases or no alteration in calcium release may be produced. The demonstration of such 'windows' suggests that many of the apparent inconsistencies in the literature may be due to the presence of such 'intensity windows' where one group has unknowingly performed its experiments within such a window, whereas another group, equally unknowingly, has performed its experiments outside of the window. Two other important aspects of this report are that firstly, the phenomenon is seen in vitro, thereby eliminating behavioral influences, and secondly, it is seen at frequencies to which we are environmentally exposed. This is a complex area which has suffered in the past from the difficulty of obtaining reproducible effects in reproducible systems. The demonstration of clear, physiological or pharmacological effects of electromagnetic radiation in relatively simple in vitro systems can only provide an added stimulus to progress in this area. RYAN J. HUXTABLE AND W. MARK LAFRANCONI

Department of Pharmacology, University of Arizona, Health Sciences Center, Tucson, A Z 85724, USA.

Reading list 1 Adey, W. R. (1981)Physiol. Reviews 61,435-514 2 Reichm~is, T. M., Perry, F. S., Marino, A. A. and Becker, R. O. (1979) Physiol. Chem. Phys. 11, 395--403 3 Lymangrover, J. R., Keku, E. and Seto, Y. J. (1983) Life Sci. 32, 691-696 4 Bawin, S. M. and Adey, W. R. (1976) Proc. Nail Acad. Sci. USA 73, 1999-2003 5 Bawm, S M., Kaczmarek, L. K. and Adey, W. R. (1975)Ann. N Y Acad. Sci. 247, 74-81

Computer Club The w o r m o f p h a r m a c o l o g y c o m p u t i n g

A computer program for multigroup comparisons One of the statistical procedures which all researchers use is Student's ' f test which is used to compare the means of two groups. However, experiments are often designed so that there are more than two groups which must be compared and, although the 't' test is inappropriate to use for multigroup comparisons, it seems many scientists still use it in these situations1. Perhaps this is based on a lack of knowledge of the proper tests, or a fear of the complexity of

the calculations. The program developed by this author will help in alleviating these problems and will allow scientists to use valid statistical tests for multigroup comparisons.

P r o g r a m requirements This program was developed on an Apple 1I plus, with 48K memory and one disk drive. It is written in Applesoft Basic and will probably work on any memory size