ID Number		345
Study Type		In Vitro
Model		1800 MHz (GSM), 50 Hz (power line) exposure to primary cells and cell lines and analysis of gene expression and differentiation
Details		Mouse embryonic Stem (ES) cells and cells of differentiated endoderm, neuroectoderm, and mesoderm stages (EBs) in culture were exposed to 1800 MHz (GSM) for 22 or 40 hours at 2 W/kg in a waveguide exposure system (cells were also exposed to 50 Hz ELF with similar results that are not described in detail here). Analysis of cell cycle (by flow cytometry) and mRNA expression of c-fos, c-jun, c-myc, p53, p21, and bcl-2 indicated no effects of RF exposure on cell cycle control, proliferation, or differentiation. In related studies, P19 embryonic tumor cells (which differentiate into cardiomyocytes or neuronal cells after DMSO or RA induction), PC12 pheochromocytoma cells, and rat primary neuronal cells were exposed for 2-5 days in culture to 1800 MHz (GSM) and analyzed for developmental progression through analysis of gene expression (c-fos, c-jun, GATA4, Nkx-2.5, etc..) and neurotransmitter release (TH, AChE, ODC), and cell cycle progression. In a subsequent study performed in wt and p53 (-/-) mouse ES cells as well as embryonic carcinoma (EC) cells, a 6-hour exposure to 1800 MHz GSM signals at 2 W/kg did not produce any short-term changes in -fos, c-jun, c-myc, early growth response (egr-1), hsp70, p21, p53, bcl-2, and alpha-myosin heavy chain (alpha-MHC) mRNAs, although a long term (48-hour) exposure of p53 -/- cells resulted in transient up-regulation of c-jun, p21, and c-myc mRNA, and permanent up-regulation of hsp70 levels. No effects on wt cells, and no effects with non-modulated signals. Temperature was monitored and reported to be within +/- 0.1 degrees between sham and exposed. In earlier studies, a similar approach was used to examine the effects of 50 Hz ELF exposure on embryonic stem cells at 0.1, 1.0, or 2.3 mT using different "on-off" schemes over a 6 or 48 hour period during different stages of differentiation. Exposure at 2.3 mT for 6 hours resulted in upregulation of c-jun, p53, and egr-1 by quantitative RT-PCR analysis. In subsequent follow-on studies using ELF (50 Hz, 2 mT) and RF (1.71 GHz GSM, 1.5 W/kg) exposure, they report ELF significantly upregulated bcl-2 and bax at 4 and 11 days, downregulated GADD45 at 4 and 23 days, and had no effect on neural genes. In contrast, RF exposure upregulated bax at 4 and 17 days, upregulated GADD45 at 4 and 23 days, and downregulated Nurr1 at 4 and 7 days. Neither ELF or RF exposure for 48 hours had any effect on DNA breaks, chromosome aberrations, SCE, proliferation, apoptosis, or mitochondrial function. However, short-term (6 hours) RF exposure did result in a low and transient increase in DNA double-strand breaks.
Findings		Effects
Status		Completed With Publication
Principal Investigator		Inst Plant Genetics, Germany - wobusam@ipk-gatersleben.de
Funding Agency		EU, VERUM, Germany, REFLEX, EU 5th Framework, Europe
Country		GERMANY
References		Nikolova, T et al. FASEB J., (2005) 19:1686-1688 Czyz , J et al. Bioelectromagnetics, (2004) 25:296-307 Czyz, J et al. Mutation Research, (2003) 557:63-74 Benfante, R et al. Toxicology in vitro. , (2008) 22:1489-1495
Comments		The study was funded by the European Union's REFLEX program. The fact that they saw gene expression but no subsequent effect on apoptosis, proliferation, or chromosome aberrations suggests that the observed effects were either not real, or were not biologically relevant. The fact that DNA damage was observed with RF exposure at 6 hours but not at 48 hours also seems suspicious (I am sure they posit an increased DNA repair activity, although they did not perform any actual experiments to address that. Finally, the changes in gene expression did not follow a dose response time course, and were all well under 20% - this coupled with the measurement technique (rtPCR) not meant to be accurately quantitative to that small degree