Franzellitti, S. Valbonesi, P. Contin, A. Biondi, C., and Fabbri, E. HSP70 expression in human trophoblast cells exposed to different 1.8 GHz mobile phone signals. Radiat Res. 2008 Oct; 170(4):488-97.
Living cells respond to environmental stimuli, including electromagnetic fields (EMFs) by activating a complex network of sensing and defense mechanisms defined as stress response. The heat-shock proteins (HSPs) are regarded as important cellular stress markers and have been proposed as suitable candidates to infer the biological effects of high frequency EMFs. HSPs are expressed in almost all organisms in response to endogenous and exogenous stress stimuli. HSPs are classified into several families, of which the HSP70 family is most widely involved in cell responses to stress.
Despite the scarce experimental and epidemiological evidence, substantial public concern exists regarding possible adverse effects of electromagnetic fields (EMFs) on the reproductive outcomes. Trophoblast cells play a crucial role in maintaining placental physiology. Therefore, the study of possible effects of high frequency EMFs on trophoblast functions could provide new insights into the molecular basis of the interaction between EMFs and human reproductive tissues.
In a previous study, the authors showed that HSP70 gene and protein expression was not modified in the HTR-8SVneo cells after 1-hour exposure to amplitude-modulated 1800 MHz GSM signals at SAR of 2 W/Kg. The purpose of the present study was to investigate possible effect on cell responses for other time and RF modulation schemes.
Cells were exposed to 1800 MHz continuous-wave (CW) signal and two different GSM signal- GSM-217Hz and GSM-Talk. Duration of exposed were considered to be longer and include 4, 16, and 24 hours at SAR of 2 W/Kg. The effects on HSP70 gene and protein expression of high frequency EMFs were compared to three types of control: cells subjected to heat stress for 1 hour at 43°C (positive control); cells maintained for 1 hour at 37°C (negative control, or incubator) and sham-exposed cells.
Effects at the protein level
After exposure to heat shock, HTR-8/SVneo cells showed a significant over-expression of the inducible protein isoform (HSP70), while the constitutive protein isoform (HSC70) was unaffected. In contrast, the expression of the HSC70 and HSP70 proteins was not modified by exposure to high-frequency EMFs using the different signals and exposure periods.
Effects at the gene expression level
Despite the absence of observable changes at the protein levels, high-frequency EMF exposure induced significant alterations in HSP70 transcription in trophoblast cells. Transcription of the HSP70C gene product was significantly modified in HTR-8/SVneo cells exposed to the GSM-217Hz signal (enhanced after 24 hour exposure) and the GSM-Talk signal (reduced after 4 and 16 hours exposure), but not in the continuous-wave exposed cells. The HSP70A and HSP70B transcripts were observed only after heat shock and were never detected in the sham and negative controls or in high-frequency EMF-exposed samples. Finally, transcription of the constitutive HSC70 gene product was not affected by the high-frequency EMF.
The finding of this study is consistent with the result of the authors’ previous study and with a large body of literature showing that high-frequency EMFs did not affect HSP70 protein expression in human cells. However, some studies found a differential expression of HSP70 in cells exposed to high frequency EMF. Different exposure systems and different cell models used, along with possible uncontrolled experimental variables, may account for these different results.
In agreement with the findings of this study, no effect on the expression of the HSP70A and HSP70B gene products in human-derived glioblastoma cells was observed in a study using 4-hour exposure to a 1900 MHz pulse-modulated radiofrequency field. However, the expression of the three HSP70A, HSP70B and HSP70C gene products was increased in a study with low frequency (50Hz) exposure of HL60 cells.
The results of this study suggest that the expression analysis for multiple transcripts, though encoding the same or similar protein products, can be highly informative and may account for subtle changes not detected at the protein level.