ID Number		1265
Study Type		In Vitro
Model		915 MHz (GSM), 2 GHz (UMTS) exposure to human lymphocytes from normal and hypersensitive individuals as well as human stem cell lines (and rat thymocytes) and analysis of chromatin conformation and DNA breaks
Details		Isolated human lymphocytes from volunteers (n=7) were exposed to 915 MHz (GSM) RF in a 0.5 ml sample with an average SAR of 43 mW/kg (range 17-142 mW/kg) for 30-60 minutes in a TEM cell. A method of anomalous viscosity time dependencies (AVTD) was used to analyze chromatin integrity and condensation, with heat (42 degrees) and camptothecin (a genotoxic agent) serving as positive controls. Exposure resulted in both increases and decreases in chromatin condensation in various (but not all) donor samples, and many of the effects were similar to heating at 40-44 degrees. Pooled data analysis from all donors indicated a statistically significant effect of 1 hour MW exposure, and was interpreted by the authors as indicative of stress response and possible genotoxic effect. A similar study was performed by the researchers in lymphocytes from self reported hypersensitive individuals (n = 7) using a similar exposure system and an SAR of 37 mW/kg and compared to lymphocytes from non-hypersensitive individuals. The authors report changes in chromatin conformation / condensation and reduced levels of p53 binding protein 1 and percentage of apoptotic DNA fragmentation in both sample groups, but that the effects were not statistically different between non-hypersensitive vs. hypersensitive individuals. The authors suggest that chromatin condensation reduces the availability of DNA breaks to 53 binding protein 1 (BP1). The authors suggest these effects are similar to stress produced by heat shock, and also report that the effects of 50 Hz were similar to those reported with 915 MHz RF. Prior presentations suggested 915 MHz (GSM) and 2 GHz (UMTS) exposure could inhibit DNA repair and affect chromatin conformation in human lymphocytes, suggesting "severe stress response and/or DNA damage". It was found, however, that 905 MHz exposure did not inhibit DNA repair, and the authors suggested the effects were frequency dependent. In a related study, the authors exposed isolated lymphocytes from 5 self-reported hypersensitive men and 5 normal controls to 900 MHz using a mobile phone handset (constant output at 2 watts) at a calculated SAR of 37 mW/kg. The authors report decreases and increases in chromatin condensation that varied between different individual samples and with specific channel frequencies within the 900 MHz band. There was also a frequency dependent increase in 53BP1/gamma-H2AX foci per cell with exposure (a response similar to heating). No effects on cell viability were reported. The authors conclude that RF exposure causes stress-induced chromatin condensation that prevents enzymes from repairing DNA breaks or otherwise disrupts DNA repair machinery, and suggest a possible increased cancer risk. In a similar study reported in 2009, the authors again analyzed lymphocytes from 5 hypersensitive and 5 non-hypersensitive individuals (not clear if these were the same as above) and exposed them to 905 and 915 MHz (GSM) as well as 1947 MHz (UMTS). Exposure to 915 Mhz (GSM), but not 905 MHz (GSM), resulted in immediate chromatin condensation and decreased p53 binding protein 1 / H2AX DNA repair complexes. Exposure with 1947 MHz (UMTS) did not lead to chromatin condensation, but also inhibbited formation of DNA repair complexes. These effects lasted 3 days post-exposure. In a 2006 publication the authors report RF exposure to rat brain cells at 915 MHz for 2 hours at an SAR of 0.4 W/kg did not affect chromatin conformation or DNA damage, but changes the expression of certain genes in brain, spleen, and thymus cell samples. Namely, gene expression using Affymetrix chips showed 11 upregulated and one downreglated gene products with diverse functions. A 2010 study reported human mesenchymal stem cells and fibroblast cells exposed to either 915 (GSM) or 1947 MHz (UMTS) showed evidence of decreased localization of TP53 binding protien 1 (often found localized to areas of dsDNA breaks) that the authors suggest indicates a reduced DNA repair capability. Chronic exposures resulted in adaption in fibroblasts but not in stem cells.
Findings		Effects
Status		Completed With Publication
Principal Investigator		University Lund and Stockholm Univ, Sweden
Funding Agency		Nat'l Res Prog, Russia
Country		SWEDEN
References		Markova, E et al. Environ health Perspect., (2010) 118:394-399 Belyaev, IY et al. Bioelectromagnetics, (2009) 30:129-141 Belyaev, IY et al. IEEE Trans Microwave Theory Tech, (2000) 48:2172-2179 Markova, E et al. Environ Health Persp, (2005) 113:1172-1178 Belyaev, IY et al. Bioelectromagnetics, (2005) 26:173-184 Sarimov, R et al. IEEE Trans. Plasma Sci., (2004) 32:1600-1608 Belyaev, IY et al. Bioelectromagnetics, (1997) 18:529-530 Belyaev, I Electromagnetic Fields in Biology and Medicine (Marko S. Markov, editor)., (2015) Chapter 5:49-67 Durdik, M et al. Sci Rep., (2019) 9:16182- Belyaev, IY et al. Z Naturforsch., (1994) 49:352-358
Comments		The paper describes the SAR of 5.4 W/kg as associated with the 2 watt pulse output power, and I am somewhat unclear whether the 5.4 W/kg is only the pulse SAR (i.e., average of 0.675 W/kg) or whether the 5.4 W/kg factors in the other 7 time slots that are not transmitting. It also seems that opposite effects due to exposure are both taken as "effects" and used in the pooled data to demonstrate statistical significance. In the 2005 paper, statistical analysis, the authors used Kolmogorov-Smirnov tests, Student's t-test, Mann-Whitney U-tests, Wilcox signed ranks tests, and the Spearman rank order correlation test. The authors also report a DECREASE in p53 binding protein 1 binding, suggesting a like decrease in ds breaks, although they explain it as reduced availability to 53BP1. AVTD is described as a method of determining the rate of migration of large DNA-protein complexes in a rotating centrifuge. The migration of DNA-protein complexes apparently causes changes in the viscosity of the medium that the DNA is layered over within the test tube that can be measured by determining rotor rotation period as a function of time. Various things can change the migration rate, including DNA breaks that unwind the DNA loops. The AVTD itself rotates at a shear rate of 5.6 seconds and a shear stress of 0.007 N m. Vicosity (and thus rotation time) is always maximal at the beginning and becomes progressively less.