EXPERIMENTAL-EVIDENCE FOR 60-HZ MAGNETIC-FIELDS OPERATING THROUGH THESIGNAL-TRANSDUCTION CASCADE - EFFECTS ON CALCIUM INFLUX AND C-MYC MESSENGER-RNA INDUCTION

We tested the hypothesis that early alterations in calcium influx indu ced 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 magne tic field exposures in a specialized annular ring device (220 G (22 mT ), 1.7 mV/cm maximal E(induced), 37-degrees-C, 60 min). Ca2+ influx is a very early ST marker that precedes the specific induction of mRNA t ranscripts for the proto-oncogene c-MYC, an immediate early response g ene. In three experiments influx of Ca-45(2+) in the absence of mitoge n was similar to that in cells treated with suboptimal levels of Con-A (1 mug/ml). However, calcium influx was elevated 1.5-fold when lympho cytes were exposed to Con-A plus magnetic fields; this co-stimulatory effect is consistent with previous reports from our laboratory [FEBS L ett. 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 n on-activated cells and in suboptimally-activated cells was also simila r, which is consistent with the above calcium influx findings. Signifi cantly, lymphocytes exposed to the combination of magnetic fields plus suboptimal Con-A responded with an approximate 3.0-fold increase in b and 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 incr eased calcium influx in response to magnetic fields plus Con-A, also f ailed to exhibit an increase in total copies of c-MYC mRNA. Thus, calc ium influx and c-MYC mRNA expression, which are sequentially linked vi a the signal transduction cascade in contrast to GAPDH, were both incr eased by magnetic fields. These findings support the above ST hypothes is and provide experimental evidence for a general biological framewor k for understanding magnetic field interactions with the cell through signal transduction. In addition, these findings indicate that magneti c fields can act as a co-stimulus at suboptimal levels of mitogen; pro nounced physiological changes in lymphocytes such as calcium influx an d c-MYC mRNA induction were not triggered by a weak mitogenic signal u nless accompanied by a magnetic field. Magnetic fields, thus, have the ability to potentiate or amplify cell signaling.