Experimental evidence for 60 Hz magnetic fields operating through the signal transduction cascade

Abstract

We tested the hypothesis that early alterations in calcium influx induced by an imposed 60 Hz magnetic field are propagated down the signal transduction (ST) cascade to alter c‐MYC mRNA induction. To test this we measured both ST parameters in the same cells following 60 Hz magnetic field exposures in a specialized annular ring device (220 G (22 mT), 1.7 maximal E induced, 37°C, 60 min). Ca2+ influx is a very early ST marker that precedes the specific induction of mRNA transcripts for the proto‐oncogene c‐MYC, an immediate early response gene. In three experiments influx of 45Ca2+ in the absence of mitogen was similar to that in cells treated with suboptimal levels of Con‐A (1 ). However, calcium influx was elevated 1.5‐fold when lymphocytes were exposed to Con‐A plus magnetic fields; this co‐stimulatory effect is consistent with previous reports from our laboratory [FEBS Lett. 301 (1992) 53‐59; FEBS Lett. 271 (1990) 157‐160; Ann. N.Y. Acad. Sci. 649 (1992) 74‐95]. The level of c‐MYC mRNA transcript copies in non‐activated cells and in suboptimally‐activated cells was also similar, which is consistent with the above calcium influx findings. Significantly, lymphocytes exposed to the combination of magnetic fields plus suboptimal Con‐A responded with an approximate 3.0‐fold increase in band intensity of c‐MYC mRNA transcripts. Importantly, transcripts for the housekeeping gene GAPDH were not influenced by mitogen or magnetic fields. We also observed that lymphocytes that failed to exhibit increased calcium influx in response to magnetic fields plus Con‐A, also failed to exhibit an increase in total copies of c‐MYC mRNA. Thus, calcium influx and c‐MYC mRNA expression, which are sequentially linked via the signal transduction cascade in contrast to GAPDH, were both increased by magnetic fields. These findings support the above ST hypothesis and provide experimental evidence for a general biological framework for understanding magnetic field interactions with the cell through signal transduction. In addition, these findings indicate that magnetic fields can act as a co‐stimulus at suboptimal levels of mitogen; pronounced physiological changes in lymphocytes such as calcium influx and c‐MYC mRNA induction were not triggered by a weak mitogenic signal unless accompanied by a magnetic field. Magnetic fields, thus, have the ability to potentiate or amplify cell signaling.

Cellular target of weak magnetic fields: ionic conduction along actin filaments of microvilli

“…calcium signaling; cell differentiation; Brownian motor hypothesis; cyclotron resonance; hair cell; mechanoelectrical coupling; physiological effects MORE THAN A DECADE OF RESEARCH on field effects in biological systems has yielded rather compelling data for the involvement of the Ca 2ϩ signaling pathway as a primary and main target of magnetic fields (MFs). As first demonstrated by Liburdy and colleagues (52,53) and later on by a number of other authors, the Ca 2ϩ influx pathways of isolated or cultured cells are severely affected by rather low MF energies.The physiological relevance of this finding is high, because Ca 2ϩ represents the most important intracellular signal governing almost all physiological functions in differentiated cells. Most importantly, cytoplasmic Ca 2ϩ ultimately determines the rate of cell proliferation, which is an essential factor in the promoAddress for reprint requests and other correspondence: J. Gartzke, Bundesanstalt fü r Arbeitsschutz und Arbeitsmedizin,…”

“…calcium signaling; cell differentiation; Brownian motor hypothesis; cyclotron resonance; hair cell; mechanoelectrical coupling; physiological effects MORE THAN A DECADE OF RESEARCH on field effects in biological systems has yielded rather compelling data for the involvement of the Ca 2ϩ signaling pathway as a primary and main target of magnetic fields (MFs). As first demonstrated by Liburdy and colleagues (52,53) and later on by a number of other authors, the Ca 2ϩ influx pathways of isolated or cultured cells are severely affected by rather low MF energies.…”

Low‐frequency electromagnetic fields do not alter responses of inflammatory genes and proteins in human monocytes and immune cell lines

“…In contrast, beneficial effects of LF EMF have been reported, including decreased severity of intestinal lesions in coccidian-infected chickens , accelerated wound healing [Callaghan et al, 2008;Goudarzi et al, 2010] and accelerated bone healing in rats and humans [Grana et al, 2008;Griffin et al, 2008], and augmented response of macrophages to bacterial challenges in humans [Akan et al, 2010]. To date, no mechanism of action has been elucidated, although several possible mechanisms have been suggested, including changes in signal transduction pathways and modulation of oxygen radicals [Liburdy et al, 1993;Blank and Soo 2001;Rollwitz et al, 2004;Frahm et al, 2010]. A large variation exists in the use of signals in scientific studies for effects of LF EMF on human health.…”

Insights into electromagnetic interaction mechanisms

“…In yet another manifestation, as we note below, EM field induction of the stress protein hsp70 may provide a useful biomarker for establishing a science-based safety standard for the design of cell phones and their transmission towers. cell calcium levels (Liburdy, 1992;Liburdy et al, 1993) and increased transcript levels for the immediate early response genes myc (Lin et al, 1994(Lin et al, , 1996Jin et al, 1997), jun, and fos (Phillips et al, 1992;Rao and Henderson, 1996) and the stress response gene HSP70 . In cell-free systems, increases in enzyme reaction rates include ornithine decarboxylase (Byus et al, 1988), Na,K-ATPase, and cytochrome oxidase (Blank, 1995b;Blank and Soo, 1998).…”