73
Pulsed Electric Fields in Biological Cells and Membranes
2.2 Interaction of Electric Fields with Living Cells
Since the late 1950s, the interaction of living cells with EM fields has been the subject
of an enormous ongoing research effort. An extremely wide variety of phenomena
have being investigated. These range from cellular effects due to weak low-frequency
EM fields associated with transmission lines and household wiring (Davis et al. 1992)
to electrical trauma arising from exposure to strong electric fields (Lee and Kolodney
1987; Gaylor, Prakah-Asante, and Lee 1988; Bhatt, Gaylor, and Lee 1990; Lee, Canaday,
and Hammer 1993; Block et al. 1995). Even in the case of household wiring, a large
spectrum of situations is of interest, from commonly occurring domestic and industrial
incidents involving low-frequency main voltage to much rarer cases of radio-frequency
shock resulting from contact with very high-voltage radio masts (Hocking et al. 1994).
The field of electric field interactions with biotissues is vast and includes aspects such
as animal navigation, endogenous fields and currents, drug delivery and other medical
interventions, human health hazards from environmental and occupational EM fields
(Blank and Findl 1987; Reilly 1992; Wiltschko and Wiltschko 1995; Polk and Postow
1996) to cellular electromanipulation (Buescher and Schoenbach 2003), and cancer
therapy (Nuccitelli et al. 2006).
The influence of both EM and static magnetic fields on cells, tissues, plants, and animals has been studied (Berg 1993). Exposure to EM fields has been reported to increase
the risk of certain types of cancer, such as leukemia, cancer of the central nervous system,
and lymphoma (Wertheimer and Leeper 1979; Savitz et al. 1988). The effects of extremely
low-frequency (ELF) EM fields on biological systems have also been evaluated by various
groups (Blank 1993; Saunders, Sienkiewicz, and Kowalczuk 1991). Different targets including proliferation, enzyme reactions, biopolymer syntheses, and membrane transport have
been investigated with respect to their alteration by EM energy (Berg 1995; Goodman,
Greenbaum, and Marron 1995). For example, proliferation yield increased more than 25%
over the control when a 0.5 mT, 50 Hz EM field was added to the yeast Saccharomyces
cerelisiae (Mehedintu and Berg 1997). With Corynebacterium glutamicum, it was found
that an amplitude of 3.4 mT at a frequency of 15 Hz increased the Adenosine Triphosphate
(ATP) level more than 20% compared with the control after 8 hours of continuous exposure (Lei and Berg 1998). In another report, the colony-forming efficiency increased 40%–
70% over the control when adding a 1.1 mT, 60 Hz EM field to JB6 cells (West et al. 1994).
The earliest report of bioeffects arising from the direct application of voltage using
contact techniques (as opposed to contactless exposure using EM radiation) was in
1958. Exposure of the nodes of Ranvier to electric fields was seen to lead to some type
of “electrical breakdown” (Stampfli 1958). Almost a decade later, damaging effects of
strong electric fields on microorganisms were reported suggesting nonthermal membrane interactions (Sale and Hamilton 1967, 1968). Subsequent experiments showed
that strong electric field pulses caused molecular transport across a biological membrane (Neumann and Rosenheck 1972). Artificial planar bilayer membrane measurements provided strong support for the transient aqueous pore hypothesis (Abidor et al.
1979; Pastushenko and Chizmadzhev 1982; Melikov 2001). This evidence invoked
the structural rearrangement of membrane molecules with charging. The prominent