Global Gene Response To Electromagnetic Fields In Eukaryotic Cells

With the rapid development of electric power and wireless communication technologies over the last several decades, public concerns have been aroused about possible health effects of exposure to environmental electromagnetic fields (EMF), including extremely low frequency magnetic fields (ELF MF) emitted from power lines and radiofrequency electromagnetic fields (RF EMF) related with mobile telephony. However, it remains unclear that whether exposure to the low density of EMF can induce the adverse biological effects and its underlying mechanism. In the present study, we have investigated the effects of ELF MF and RF EMF on global gene expression in human breast cancer cell line MCF-7 and Saccharomyces cerevisia with the help of duplicate microarrays analysis followed by real-time reverse transcription polymerase chain reaction (RT-PCR) analysis with an intend to explore commons and differences of gene response to ELF MF and RF EMF as well as possible common gene response to EMF in eukaryotic cells. Part 1. Effects of ELF MF on gene expression in MCF-7 cellsIn vitro cultured MCF-7 cells were continuously exposed or sham-exposed to 0.4 mT of 50 Hz MF for 24 hours. Affymetrix Human Genome Genechips (U133A) were applied to analyze gene expression profiles in MF exposed and sham-exposed MCF-7 cells and the data were processed with the help of Genechip data analysis software MAS 5.0 and DMT 3.0. As a result, 30 differentially expressed genes were screened with 100% consistency change calls in the MF exposed MCF-7 cells. Six independent real-time RT-PCR analyses showed that SCNN1A, METTL3 and GPR137B were slightly but statistically significantly changed in MCF-7 cells after exposure to 50 Hz MF (P<0.05), while other analyzed genes exhibited slight up- and down-fluctuations in expressions and no increase or decrease in each gene expression reached statistical significance (P>0.05). In conclusion, the present study identified three ELF MF responsive genes in MCF-7 cells although 50 Hz MF exposure under current experimental conditions did not broadly change gene expression profile in MCF-7 cells. The biological consequences of expression changes in these MF responsive genes await further investigations.Part 2. Effects of GSM 1800 MHz RF EMF on gene expression in MCF-7 cells MCF-7 cells were intermittently (5 min on/ 10 min off) exposed or sham-exposed to 217 Hz modulated GSM 1800 MHz RF EMF for 24 hours at an average specific absorption rate (SAR) of 2.0 W/kg or 3.5 W/kg. U133A Genechips assays were applied to analyze the gene expression profile in RF EMF exposed or sham-exposed cells and the result of Genechip data analysis showed that no differentially expressed genes were screened out with 100% consistency change calls at SAR of 2.0 W/kg, while five up-regulated genes were screened out with 100% consistency change call atSAR of 3.5 W/kg. However, six independent real-time RT-PCR analyses showed that these five genes exhibited slight up- and down-fluctuations in expressions and no increase or decrease in each gene expression reached statistical significance (P>0.05). In conclusion, the present study did not provide clear evidence that RF EMF exposure under current experimental conditions could broadly change gene expression in MCF-7 cells.Part 3. Effects of EMF on gene expression in Saccharomyces Cerevisiae The yeast cells were continuously exposed and sham exposed to 0.4 mT 50 Hz MF or intermittently exposed and sham-exposed to GSM 1800 MHz RF EMF at SAR of 3.5 W/kg for 6 hours. Affymeteix Yeast Genome Genechips (S98) were applied to analyze gene expression profiles in the yeast cells and the data were processed with the help of the software GCOS 1.0 and DMT 3.0. As a result, three up-regulated genes and 40 differentially expressed genes were screened out with 100% consistency change calls in yeast cells after exposure to 50 Hz MF and RF EMF, respectively. Six independent real-time RT-PCR analyses showed that SMC3, AQY2 (m), HAL9, YAK1 and a function unknown gene (ORF: YJL171C) were slightly but statistically significantly changed in yeast cells after exposure to RF EMF (P＜0.05), while other analyzed RF EMF responsive candidate genes and three MF responsive candidate genes exhibited slight up- and down-fluctuations in expressions and no increase or decrease in each gene expression reached statistical significance (P>0.05). In addition, SMC3 and YAK1 were found orthologs in human. In conclusion, the present study identified five RF EMF responsive genes although either RF EMF or 50 Hz MF exposure did not broadly change gene expression profile in Saccharomyces Cerevisiae under currentexperimental conditions. The biological consequences of expression changes in these RF EMF responsive genes need to be further investigated.Overall, the present study did not provide clear evidence that exposure to 50 Hz MF and GSM 1800 MHz RF EMF could broadly change gene expression in MCF-7 cells and Saccharomyces Cerevisiae under current experimental conditions. However, SCNN1A, METTL3 and GPR137B were slightly but statistically significantly changed in MCF-7 cells after exposure to 50 Hz MF (P＜0.05), while SMC3, AQY2 (m), HAL9, YAK1 and a function unknown gene (ORF. YJL171C) were slightly but statistically significantly changed in Saccharomyces Cerevisiae after exposure to RF EMF, of which SMC3 and YAK1 were found orthologs in human. The slightly gene expression changes in MCF-7 cells and Saccharomyces Cerevisiae responding to EMF may attribute to the followings: 1) these two types of cells seemed "less sensitive" to EMF exposure, 2) the cells may adapt to EMF exposure, 3) the microarray analysis may be not sensitive enough to detect the weak response of these cells to EMF exposure.The following novel findings were drawn based on the data:The present study firstly evaluated global gene response to both ELF MF and RF EMF exposure in MCF-7 cells and Saccharomyces Cerevisiae, and demonstrated that EMF exposure did not broadly change gene expression in these two types of cells under current experimental conditions.The present study firstly identified three 50 Hz MF slightly responsive genes in MCF-7 cells including SCNN1A, METTL3 and GPR137B, and five GSM 1800 MHzRF EMF slightly responsive genes in Saccharomyces Cerevisiae including SMC3,AQY2 (m), HAL9, YAK1 and a function unknown gene (ORF: YJL171C).By combination of microarray analysis with real-time RT-PCR analysis, the presentstudy firstly systemically evaluated the cellular transcriptome response to both ELFMF and RF EMF to compare the commons or differences of gene expression responseto ELF MF and RF EMF in MCF-7 cells as well as those in SaccharomycesCerevisiae.The present study firstly investigated the global gene response to both ELF MF andRF EMF in both yeast and human cells, and identified the human orthologs of two RFEMF responsive genes in Saccharomyces Cerevisiae, which would be helpful toexplore the possible common gene response to EMF in eukaryotic cells.