NF‐κB DNA‐binding activity after high peak power pulsed microwave (8.2 GHz) exposure of normal human monocytes

Abstract

The hypothesis investigated is that exposure of a mammalian cell to high peak power pulsed RF, at the frequency of 8.2 GHz, can result in the activation of an important eukaryotic transcriptional regulator, nuclear factor kappa B (NF-kappaB). This DNA-binding protein controls genes involved in long term cellular regulation. The selection of 8.2 GHz was based on the availability of a high peak power pulsed RF transmitter. In these studies, triplicate cultures of human monocytes (Mono Mac-6) were exposed to the pulsed wave radiation. The peak to average power ratio was 455:1 (2.2 micros pulse width and pulse repetition rate of 1000 pulses/s). The average power density at the position of exposure was 50 W/m(2), and the mean SAR at the bottom of the culture flask was 10.8 +/- 7.1 W/kg. The FDTD analysis indicated that 10% of the cells had an SAR of 22-29 W/kg. The cells were exposed continuously for 90 min at 37 degrees C, reincubated at this temperature, and harvested 4 h postexposure. The nuclear extracts were analyzed by electrophoretic mobility shift assay. The results showed a profound increase (3.6-fold) in the DNA binding activity of NF-kappaB in monocytes at 4 h after the pulsed RF exposure compared to sham irradiated controls. Competition experiments with cold NF-kappaB- specific oligonucleotides confirmed the specificity of the DNA binding activity. These results provide evidence that high peak power pulsed radiofrequency radiation can perturb the cell and initiate cell signaling pathways. However, at this point, we are not prepared to advocate that the cause is a nonthermal mechanism. Because of the broad distribution of SAR's in the flask, experiments need to be performed to determine if the changes observed are associated with cells exposed to high or low SARs.

Nuclear Translocation and DNA-Binding Activity of NFKB (NF-κB) after Exposure of Human Monocytes to Pulsed Ultra-wideband Electromagnetic Fields (1 kV/cm) Fails to Transactivate κB-Dependent Gene Expression

“…The findings raise the possibility that multi-frequency presentation of the radiant energy with a picosecond rise time and an extremely short pulse width (lasting nanoseconds) may be sufficient to trigger cell signaling and lead to an early step in the initiation of transcriptional activation. While it can be argued that the occurrence of a thermal gradient, as well as the exposure of a proportion of the cells at a very high SAR, could have influenced the induction of NFKB activation under these exposure conditions, we and others have reported previously that an increase in temperature only negates the activity of NFKB and does not elevate DNAbinding activity (11,(32)(33)(34)(35).…”

“…Recently, a few attempts (including our own) have been made to study the initiation of the NFKB signaling pathway in both human and other mammalian cell types after exposure to radiofrequency and extremely lowfrequency EMFs (11,30,31). In a previous study (11), we demonstrated that the cells exposed to a pulsed high-peakpower ultra-wideband EMF for 90 min and incubated for 24 h postexposure exhibited more than a 3.5-fold increase in the prototypical NFKB complex (NFKB p50/p65) compared to sham-exposed controls. To our knowledge, this study is the first demonstration of NFKB DNA-binding activity after any ultra-wideband EMF exposure.…”

“…NFKB exists in the cytoplasm as an inactive complex in association with the inhibitor protein subunit IKB (I-B) (20)(21)(22)(23). Its activation is triggered by a number of conditions and agents in intact mammalian cells (10)(11)(12)(13)(14)(15)(16)23). Once induced, this pathway precedes by phosphorylation of the inhibitor subunits I-B␣ and I-B␤.…”

Molecular Mechanisms Contributing to the Growth and Physiology of an Extremophile Cultured with Dielectric Heating

“…However, confirmation that a biological effect results from exposing live cells to an electromagnetic field has yet to be definitively demonstrated. Most studies to date involving the physiological or transcriptional effects of microwave radiation on living microorganisms have been performed with mesophilic bacteria, archaea (6), and select eukaryotic systems (7,8). The selection of mesophilic organisms coupled with highly varied experimental designs were practical considerations used to generate each individual result.…”

Lack of direct DNA damage in human blood leukocytes and lymphocytes after in vitro exposure to high power microwave pulses

“…HPMP exposure ceased the individual development of Drosophila [Bolshakov et al, 2000[Bolshakov et al, , 2001a, inhibited a growth rate of fungus Fusarium sp., and suppressed a level of RNA and DNA synthesis in tumor cells of mastocytoma P-815 [Bolshakov et al, 2000[Bolshakov et al, , 2001b. Natarajan et al [2002] showed that exposure of human cells to HPMP can increase DNA binding activity of NF-kB, which can then transactivate the expression of its target genes and thereby change the chromatin structure. As for the direct genotoxic effects of HPMP exposure, the literature data are unavailable if present at all.…”