Biological Effects of Nonionizing Radiation - American Chemical Society

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8 Dielectric Properties of Biological Tissue and Biophysical Mechanisms of ElectromagneticField Interaction Downloaded by UNIV OF MISSOURI COLUMBIA on August 5, 2013 | http://pubs.acs.org Publication Date: August 4, 1981 | doi: 10.1021/bk-1981-0157.ch008

H. P. SCHWAN Department of Bioengineering/D3, University of Pennsylvania, Philadelphia, PA 19104 The propagation of electromagnetic waves i n t i s s u e s i s de­ termined by t h e i r e l e c t r i c a l p r o p e r t i e s . I n a d d i t i o n , these p r o p e r t i e s t e l l us much about the mechanism of i n t e r a c t i o n of electromagnetic f i e l d s w i t h v a r i o u s b i o l o g i c a l systems, i n c l u d i n g biopolymers, membranes, and c e l l s . Our present-day knowledge of the e l e c t r i c a l p r o p e r t i e s i s r a t h e r advanced (1), and I s h a l l f i r s t summarize the s t a t e of our present knowledge of such prop­ e r t i e s . Then I s h a l l draw some conclusions about p o s s i b l e mechanisms which may o r may not g i v e cause t o s u b t l e nonthermal effects. No c o n s i d e r a t i o n w i l l be given t o magnetic p r o p e r t i e s s i n c e the l a t t e r a r e , f o r our purposes, i d e n t i c a l t o those of f r e e space. E l e c t r i c a l Properties We w i l l summarize the two e l e c t r i c a l p r o p e r t i e s which d e f i n e the e l e c t r i c a l c h a r a c t e r i s t i c s , namely, the d i e l e c t r i c constant r e l a t i v e t o f r e e space ε and the c o n d u c t i v i t y σ. Both p r o p e r t i e s change w i t h temperature and s t r o n g l y w i t h frequency. As a matter of f a c t , as the frequency increases from a few Hertz t o g i g a h e r t z , the d i e l e c t r i c constant decreases from s e v e r a l m i l l i o n t o only a few u n i t s . C o n c u r r e n t l y , the c o n d u c t i v i t y increases from a few mMho/cm t o n e a r l y a thousand. F i g u r e 1 i n d i c a t e s the d i e l e c t r i c behavior o f p r a c t i c a l l y a l l t i s s u e s . Two remarkable features are apparent: exceedingly h i g h d i e l e c t r i c constants a t low frequencies and three c l e a r l y separated r e l a x a t i o n regions a, 3, γ of the d i e l e c t r i c constant at low, medium, and very h i g h f r e q u e n c i e s . Each o f these r e ­ l a x a t i o n regions i s i n i t s s i m p l e s t form c h a r a c t e r i z e d by equa­ t i o n s o f the Debye type

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In Biological Effects of Nonionizing Radiation; Illinger, K.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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RADIATION

Plenum Publishing Company Figure 1.

Frequency dependence of the dielectric constant of muscle tissue (61).

Dominant contributions are responsible for the α, β, and γ dispersions. They include for the α-effect, apparent membrane property changes as described in the text; for the β-effect, tissue structure (Maxwell-Wagner effect); and for the y-effect, polarity of the water molecule (Debye effect). Fine structural effects are responsible for deviations as indicated by the dashed lines. These include contributions from subcellular organelles, proteins, and counterion relaxation effects (see text).

In Biological Effects of Nonionizing Radiation; Illinger, K.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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determined by the values a t the beginning and the end o f the d i s person change. However, b i o l o g i c a l v a r i a b i l i t y may cause the a c t u a l data t o change w i t h frequency somewhat more smoothly than i n d i c a t e d by the equations. TABLE I E l e c t r i c a l R e l a x a t i o n Mechanism (61)

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Inhomogeneous S t r u c t u r e

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(See Text) Plenum Publishing Company

Three c a t e g o r i e s o f r e l a x a t i o n e f f e c t s are l i s t e d as they con­ t r i b u t e t o gross and f i n e s t r u c t u r e r e l a x a t i o n a l e f f e c t s . They i n c l u d e induced d i p o l e e f f e c t s (Maxwell-Wagner and counterion) and permanent d i p o l e e f f e c t s (Debye).

The s e p a r a t i o n o f the r e l a x a t i o n regions g r e a t l y a i d s i n the i d e n t i f i c a t i o n o f the u n d e r l y i n g mechanism. The mechanisms r e ­ s p o n s i b l e f o r these three r e l a x a t i o n regions are i n d i c a t e d i n Table I . Inhomogeneous s t r u c t u r e i s r e s p o n s i b l e f o r the 3~ d i s p e r s i o n , i . e . , the p o l a r i z a t i o n r e s u l t i n g from the charging of i n t e r f a c e s , i . e . , membranes through i n t r a - and e x t r a c e l l u l a r f l u i d s (Maxwell-Wagner e f f e c t ) . A t y p i c a l example i s presented i n Figure 2 i n the form o f an impedance l o c u s . The d i e l e c t r i c p r o p e r t i e s of muscle t i s s u e are seen t o c l o s e l y conform t o a suppressed c i r c l e , i . e . , t o a Cole-Cole d i s t r i b u t i o n f u n c t i o n of r e l a x a t i o n times. A s m a l l second c i r c l e a t low frequencies represents the α-dispersion e f f e c t . R o t a t i o n o f molecules having a permanent d i p o l e moment such as water and p r o t e i n s i s r e s p o n s i b l e f o r the γ-dispersion (water) and a s m a l l a d d i t i o n to the t a i l o f the 3 - d i s p e r s i o n r e s u l t i n g from a corresponding 3 i ~ d i s p e r s i o n of p r o t e i n s . The t i s s u e p r o t e i n s only s l i g h t l y e l e v a t e the h i g h frequency t a i l o f the t i s s u e ' s 3 - d i s p e r s i o n s i n c e the a d d i t i o n o f the 3 - - e f f e c t caused by t i s s u e p r o t e i n s i s s m a l l compared t o the Maxwell-Wagner e f f e c t and s i n c e i t occurs a t somewhat higher f r e q u e n c i e s . Another c o n t r i b u t i o n t o

In Biological Effects of Nonionizing Radiation; Illinger, K.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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the 3-dispersion i s caused by smaller subcellular structures, such as mitochondria, c e l l nuclei, and other subcellular organ­ elles. Since these structures are smaller i n size than the surrounding c e l l , their relaxation frequency i s higher, but their total dielectric increment smaller. They, therefore, contribute another addition to the t a i l of the 3-dispersion ( 3 ^ ) . The γ-dispersion i s solely due to water and i t s relaxational behavior near about 20 GHz. A minor additional relaxation (δ) between 3 and γ-dispersion i s caused in part by rotation of amino acids, partial rotation of charged side groups of proteins, and the relaxation of protein bound water which occurs somewhere between 300 and 2000 MHz. The α-dispersion i s presently the least c l a r i f i e d . Intra­ cellular structures, such as the tubular apparatus in muscle c e l l s , which connect with the outer c e l l membranes, could be re­ sponsible in a l l such tissues which contain such c e l l structures. Relaxation of counterions about the charged cellular surface i s another mechanism suggested by us. Last, but not least, relaxa­ tional behavior of membranes per se, such as reported recently for the giant squid axon membrane, can account for i t (2). The relative contribution of the various mechanisms varies, no doubt, from one case to another and needs further elaboration. No attempt i s made to summarize conductivity data. Conduc­ t i v i t y increases similarly in several major steps symmetrical to the changes of the dielectric constant. These changes are i n accord with the theoretical demand that the ratio of capacitance and conductance changes for each relaxation mechanism i s given by i t s time constant, or, in the case of distributions of time con­ stants, by an appropriate average time constant and the KramersKronig relations. Table II indicates the v a r i a b i l i t y of the characteristic frequencies for the various mechanisms a, 3 , Ύ and kT, (where y i s the d i p o l e moment, Ε the f i e l d s t r e n g t h , k i s the Boltzman constant, and Τ i s the absolute temperature). Thus l a r g e r p h y s i c a l dimensions or l a r g e r perma­ nent or induced d i p o l e moments are more l i k e l y to respond to weak fields. The l a r g e dimensions necessary f o r b i o l o g i c a l responses to weak microwave f i e l d s might be achieved by a cooperative r e a c t i o n of a number of c e l l s or macromolecules to the microwave s t i m u l u s , which i n c r e a s e s the e f f e c t i v e s i z e of the s t r u c t u r e and c o r r e s ­ pondingly reduces the t h r e s h o l d that i s r e q u i r e d f o r an e f f e c t . Adey suggested that such c o o p e r a t i v i t y might be induced i n the counterions l o o s e l y bound near membrane s u r f a c e s which c o n t a i n a loose frame work of charged p o l y s a c c h a r i d e s (32). F r o e h l i c h has suggested (55, 56) that giant d i p o l e moments may be formed during enzyme s u b s t r a t e r e a c t i o n s and that the corresponding d i e l e c t r i c a b s o r p t i o n processes might be h i g h l y resonant and n o n l i n e a r , and l i k e l y to channel energy i n t o lower frequency modes of v i b r a t i o n . He a l s o considered the membrane as a l i k e l y s i t e of resonant electromagnetic (EM) i n t e r a c t i o n s , and d e r i v e d an estimate of the resonant frequencies from the v e l o c i t y of sound and the membrane thickness to be of the order of 100 GHz. A c c e l e r a t i o n and d e c e l e r a t i o n of a v a r i e t y of b i o ­ l o g i c a l responses which suggest resonances have been reported by Webb (57), Devyatkov (58), and, more r e c e n t l y , by Grundler et a l . (59) i n the m i l l i m e t e r frequency range. But some of these s t u d i e s have been c r i t i c i z e d on t e c h n i c a l grounds, and the Rus­ s i a n work, only summarized i n 1974, has not yet been p u b l i s h e d in detail. Gandhi has conducted continuous d i e l e c t r i c s p e c t r o s ­ copy measurements at millimeter-wave frequencies with no i n d i c a ­ t i o n s of any resonance processes (60). He a l s o found no e f f e c t s of millimeter-wave r a d i a t i o n on a v a r i e t y of c e l l u l a r processes which were not a t t r i b u t a b l e to sample h e a t i n g . But the resonance phenomena r e p o r t e d by Grundler and Keilmann and p o s t u l a t e d by F r o e h l i c h may only i n v o l v e a minor f r a c t i o n of the t o t a l c e l l u l a r

In Biological Effects of Nonionizing Radiation; Illinger, K.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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e n t i t y and, hence, not demonstrate i t s e l f s t r o n g l y enough to be observed i n the bulk d i e l e c t r i c data.

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Abstract The dielectric properties of tissues and cell suspensions will be summarized for the total frequency range from a few Hz to 20 GHz. Three pronounced relaxation regions at ELF, RF and MW frequencies are due to counterion relaxation and membrane invaginations, to Maxwell-Wagner effects, and to the frequency dependent properties of normal water at microwave frequencies. Superimposed on these major dispersions are fine structure effects caused by cellular organelles, protein bound water, polar tissue proteins, and side chain rotation. Insight into the biophysical mechanism of EM-field interactions is gained from the understanding of these dielectric properties. At ELF frequencies cells sample the external field over their dimensions and apply the resulting potential to the membranes with cut-off frequencies extending up to the RF range. Tissue water appears to be identical in its dielectric properties with normal water, except for a small fraction of protein bound water. Field effects on large biopolymers are indicated only at field values above 10 kV/cm, but field induced dipole effects on large cells are possible at considerably lower values. More subtle field interactions with biological matter require either cooperative interactions or very large dipole moments so far not yet identified. Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10.

11.

Schwan, H.P. Adv. Biol. Med. Phys., 1957, 5, 147. Academic Press: New York. Takashima, S.; Schwan, H.P. J . Membr. Biol., 1974, 17, 51. Afsar, M.N.; Hasted, J.B. J . Opt. Soc. Amer., 1977, 67, 902. Hasted, J.B. "Aqueous Dielectrics"; Chapman and Hall: London, England. Pauly, H.; Schwan, H.P. Biophys. J., 1966, 6, 621. Herrick. J . F . ; Jelatis, D.G.; Lee, G.M. Fed. Proc., 1950, 9., 60. Schwan, H.P.; Foster, K.R. Biophys. J., 1977, 17, 193. Foster, K.R.; Schepps, J . L . ; Schwan, H.P. Biophys. J . , 1980, 29, 271. Schwan, H.P.; Foster, K.R. Proc. IEEE, 1980, 68, 104. Takashima, S. "Dielectric Properties of Proteins. I. Dielectric Relaxation." In: Leach, J . S . , Ed. "Physical Principles and Techniques of Protein Chemistry"; Academic Press: New York, 1969. Takashima, S.; Minikata, A. "Dielectric Behavior of Biological Macromolecules." In: "Digest of Dielectric Literature"; National Research Council: Wash., DC, V. 37, 1975, p. 602.

In Biological Effects of Nonionizing Radiation; Illinger, K.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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Schwan, H.P. Ann. N.Y. Acad. Sci., 1965, 125, 344. Pennock, B.E.; Schwan, H.P. J . Phys. Chem., 1969, 73, 2600. Grant, E.H.; Keefe, S.E.; Takashima, S. J . Phys. Chem., 1968, 72, 4373. Grant, E.H. "Determination of Bound Water in Biological Materials." In: Proc. Workshop Physical Bases of Electromagnetic Interactions with Biological Systems, University of Maryland, 1979, p. 113. Schwan, H.P. "Classical Theory of Microwave Interactions with Biological Systems." In: Proc. Workshop Physical Bases of Electromagnetic Interactions with Biological Systems, University of Maryland, 1977, p. 90. Jones, G.P.; Gregson, M.; Davies, M. Chem. Phys. Lett., 1969, 4, 33. Illinger, K.H. "Millimeter-wave and Far-infrared Absorption in Biological Systems." In: Taylor, L . S . ; Cheung, A.Y., Eds., "The Physical Basis of Electromagnetic Interactions with Biological Systems, Proc. Workshop"; University of Maryland, 1977, p. 43. Rosskey, P . J . ; Karplus, M. J . Amer. Chem. Soc., 1979, 101, 1913. Froehlich, H. "Theory of Dielectrics"; Oxford University Press: Oxford, England, 1949. Fricke, H. Phys. Rev., 1923, 21, 708. Cole, K.S. "Membranes, Ions and Impulses"; University of California Press: Berkeley, Ca., 1972. Schwan, H.P.; Morowitz, H.J., Biophys. J., 1962, 2, 395. Schwan, H.P.; Takashima, S.; Miyamoto, V.K.; Stoeckenius, W. Biophys. J., 1970, 10, 1102. Pauly, H.; Schwan, H.P. Z. Naturforsch., 1959, 14b, 125. Schwan, H.P. J . Cell Compar. Phys., 1965, 66, 5. Schmitt, F.O.; Dev, P.; Smith, B.H. Science, 1976, 193, 114. Schwan, H.P. NWL Tech. Report, TR-2713, U.S. Naval Weapons Lab.: Dahlgren, Va., 1972. "Biological Effects of Electric and Magnetic Fields Associated with Proposed Project Seafarer"; National Academy of Sciences-National Research Council: Wash., DC, 1977. Schwan, H.P. IEEE Trans., 1971, MTT-19, 146. Kalmijn, A . J . Nature, 1966, 212, 1232. Bawin, S.M.; Adey, W.R. Proc. Nat. Acad. Sci. USA, 1976, 73, 1999. Gavalas-Medici, R.; Day-Magdaleno, S.R. Nature, 1976, 261, 265. Baranski, S.; Czerski, P. "Biological Effects of Microwaves"; Dowden, Hutchinson and Ross., Inc.: Stroudsburg, Pa. 1976. Frey, A.H. IEEE Trans., 1971, MTT-19, 153. Bawin, S.M.; Adey, W.R. Neurosci. Res. Prog. Bull., 1977, 15, 1. Roy, O.Z.; Scott, J.R.; Park, G.C. IEEE Trans., 1976, BME-23, 45.

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In Biological Effects of Nonionizing Radiation; Illinger, K.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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Driscoll, D.A. "An Investigation of a Theoretical Model of the Human Head with Application to Current Flow Calculations and EEG Interpretation"; Ph.D. Thesis, University of Vermont, 1970. Zimmerman, U.; Pilwat, G.; Riemann, R. Biophys. J . , 1974, 14, 881. Neumann, E . ; Rosenheck, K. J . Memb. Biol., 1972, 10, 279. Friend, A.W.; Finch, E.D.; Schwan, H.P. Science, 1974, 187, 357. Goodman, E.M.; Greenebaum, B.; Marron, M.T. "Effects of Extremely Low Frequency Electromagnetic Fields on Growth and Differentiation of Physarum polycephalum"; Technical Report Phase I (Continuous Wave), University of Wisconsin, 1975. Goodman, E.M.; Greenebaum, B.; Marron, M.T. "Effects of Extremely Low Frequency Electromagnetic Fields on Physarum polycephalum"; Technical Report, Office of Naval Research, Contract N-00014-76-C-0180, Univ. of Wisconsin, 1976. Teixeira-Pinto, A.A.; Nejelski, L . L . ; Cutler, J . L . ; Heller, J.H. Exp. Cell Res., 1960, 20, 548. Sher, L.L. Ph.D. Thesis, "Mechanical Effects of AC Fields on Particles Dispersed in a Liquid: Biological Implications"; University of Pennsylvania: Philadelphia, Pa. 1963. Novak, B.; Bentrup, F.W. Biophysik, 1973, 9, 253. Pohl, H.A. J . Biol. Phys., 1973, 1, 1. Elul, R. J . Physiol., 1967, 189, 351. Schwan, H.P. Ann. N.Y. Acad. Sci., 1977, 303, 198. Blakemore, R. Science, 1975, 190, 377. Sher, L.D.; Kresch, E . ; Schwan, H.P. Biophys. J . , 1970, 10, 970. Sher, L.D. Nature, 1968, 220, 695. Schwarz, G. J . Chem. Phys., 1963, 39, 2387. Schwan, H.P.; Sher, L.D. J . Electrochem. Soc., 1969, 116, 170. Froehlich, H. Proc. Nat. Acad. Sci. USA, 1975, 72, 4211. Froehlich, H. Coll. Phen., 1973, 1, 101. Webb, S.J.; Booth, A.D. Science, 1971, 174, 72. Devyatkov, N.D. Sov. Phys. USPEKHI, 1974, 16, 568 (Transl.). Grundler, W.; Keilmann, F . ; Froehlich, H. Phys. Lett., 1977, 62A, 463. Gandhi, O.P.; Hagmann, M . J . ; Riazi, A . ; H i l l , D.W.; Partlow, L.M. "Millimeter Wave and Raman Spectra of Living Cells Some Problems and Results"; presented at the Workshop on Mechanisms of Microwave Biological Effects, University of Maryland, May 14-16, 1979. Schwan, H.P. "Dielectric Properties of Biological Materials and Interaction of Microwave Fields at the Cellular and Molecular Level"; In: Michaelson, S.M.; Miller, M.W., Eds. "Fundamental and Applied Aspects of Nonionizing Radiation"; Plenum Pub1. Co.: New York, 1975.

RECEIVED October 31,

1980.

In Biological Effects of Nonionizing Radiation; Illinger, K.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.