The figure at the right shows electrically induced cell dedifferentiation of human red blood cells obtained from a patient who was scheduled for surgery. The presence of a large number of dedifferentiated immature red blood cells indicates that the patient may have other serious health problems.
Clockwise from upper left: scanning electron microscope (SEM) image (X 2,500 magnification) of a red blood cell with the classic donut shape. This cell has not been electrically stimulated. The next group of red blood cells (X 1,500), at the upper right, shows how initial exposure to 1 µA of direct current has produced an alteration of the concave region in the middle of the cell, along with the appearance of thin radiating structures (or spokes) that have been shown by both Becker (N.Y. Academy of Sciences paper) and Nordenström (1983 BCEC book). After longer exposure to a 1 µA direct current (lower right), some of the red blood cells revert even further to an elongated elliptical shape (X 1,600). As the cells are exposed to a 1 µA direct current over a longer time period (lower left), they begin to exhibit the flat amoeboid morphology (X 1,500) described by Becker in his book, The Body Electric.
The process of dedifferentiation, or reversion, was evident with some of the lymphoma cells. As they were exposed to direct electric current (approximately 9 µA) for longer periods of time (16 hours or more), the lymphoma cells appeared to lose their aggregation properties. This indicates that the lymphoma cells may be experiencing some kind of electrically induced reversion process, where they lose some of their malignancy properties and begin to acquire some of the contact inhibition exhibited by normal cells.
It is apparent that when electric current passes through diseased and normal tissue, there is a lot more activity than just the five mechanisms listed above. Over the past 33 years, a wide variety of research results concerning direct current and static electric field interactions with living matter strongly indicate that one of the primary interaction and cell growth mechanisms involves receptor mediated activity and ion channel modifications (see Polk and Postow, Handbook of Biological effects of Electromagnetic fields, CRC Press (1986)). Poo, et. al. have reported that the distribution of acetylcholine (ACh) and concanavalin A (Con A) receptors can be changed by the application of electric fields in the 1 V/cm to 10 V/cm range. Electric fields in the 0.1 V/cm to 10 V/cm range can also have significant effects on the growth of neurites obtained from single neurons in culture.
Viega, et. al. (Bioelectromagnetics, Vol. 21, 2000) reported variations in membrane surface carbohydrate expression, distribution of anionic sites and modulation of Con A, sialic acid and specific lectin binding to the cell surface after direct electric current was applied. Cheng et. al. (Clinical Orthopaedics and Related Research, No. 171, 1982) reported significant variations in ATP generation, protein synthesis and membrane transport in murine tissue with the application of direct electric current.
The reverse transcriptase polymerase chain reaction (RT-PCR) technique was utilized to measure the production of certain cytokines from macrophages under the influence of low-level direct currents. No interleukin 1 (IL-1) or tumor necrosis factor (TNF) output was detected. However, IL-8 modulation by direct electric current was detected. In this case, a very light IL-8 band was noticed at a direct current level of 5 µA, while no IL-8 band was observed for the lower direct current of 0.55 µA and the 0 A control. Therefore, it would appear that some immunologically important cell membrane receptors are sensitive to a certain range of low-level direct currents.
There are a variety of other cell membrane structures that can be influenced by an electric field, accumulated charge or electric current. These include: 1) Cyclic AMP receptor - Impacts glycolysis, cell aggregation, cell differentiation, cell proliferation and inhibits tumor growth in mammalian cells, 2) Glucocorticoid receptor - Regulates gene transcription, cell differentiation and proliferation, 3) Na/H antiporter - Regulates cell pH in virtually all cells, 4) Ion channels - Control cell pH, membrane polarity and some membrane transport activity.
Therefore, the therapeutic effects from the application of an EChT current will have significant effects on a wide variety of simultaneous events and mechanisms, including: influences on tumor tissue and structure, tumor pH control (at the tissue and cellular levels), transport of water and nutrients to the tumor site, tumor vascular structure, red blood cell function in the tumor region, tumor cell proliferation, cell differentiation/dedifferentiation and the movement, function and output of various cells in the immune system.
From: R.O.Becker and D.G. Murray, Transactions of the New York Academy of Sciences, Vol. 29, 1967; M.M. Poo, W.J. Poo and J.W. Lam, Journal of Cell Biology, Vol. 76, 1978; N. Cheng, et. al. Clinical Orthopaedics and Related Research, No. 171, 1982; B.E.W. Nordenström, Biologically Closed Electric Circuits, Nordic Medical Publications, Stockholm (1983); R.O. Becker and G. Selden, The Body Electric, William Morrow, New York (1985); G.D. O'Clock, Proceedings of the Fourth International Symposium on Biologically Closed Electric Circuits, October 26-29, 1997; C.K. Chou, et.al., Bioelectromagnetics, Vol. 18, 1997; Y. Yen, et.al., Bioelectromagnetics, Vol. 20, 1999; E. Nilsson, Modelling of the Electrochemical Treatment of Tumours, Doctoral Thesis, Royal Institute of Techlology, Stockholm, 2000; V.F. Viega, et. al., Bioelectromagnetics, vol. 21, 2000; G.D. O'Clock, German Journal of Oncology, Vol. 33, 2001; G.D. O'Clock and T. Leonard, German Journal of Oncology, Vol. 33, 2001; H. von Euler, E. Nilsson, J.M. Olsson and A.S. Lagerstedt, Bioelectrochemistry, vol. 54, 2001; B.E.W Nordenström, Journal of the IABC, Vol. 1, January-December, 2002; Ito, et.al., Journal of the IABC, Vol. 1, January-December, 2002; H. von Euler, H. Soderstedt, A. Thorne, J.M. Olsson and G. Yongquing, Bioelectrochemistry, vol. 58, 2002; G.D. O'Clock, Electrotherapeutic Devices: Principles, Design and Applications, Artech House, Boston, MA (2007).