Whole‐genome expression analysis in primary human keratinocyte cell cultures exposed to 60 GHz radiation

The main purpose of this study is to investigate potential responses of skin cells to millimeter wave (MMW) radiation increasingly used in the wireless technologies. Primary human skin cells were exposed for 1, 6, or 24 h to 60.4 GHz with an average incident power density of 1.8 mW/cm2 and an average specific absorption rate of 42.4 W/kg. A large‐scale analysis was performed to determine whether these exposures could affect the gene expression. Gene expression microarrays containing over 41,000 unique human transcript probe sets were used, and data obtained for sham and exposed cells were compared. No significant difference in gene expression was observed when gene expression values were subjected to a stringent statistical analysis such as the Benjamini–Hochberg procedure. However, when a t‐test was employed to analyze microarray data, 130 transcripts were found to be potentially modulated after exposure. To further quantitatively analyze these preselected transcripts, real‐time PCR was performed on 24 genes with the best combination of high fold change and low P‐value. Five of them, namely CRIP2, PLXND1, PTX3, SERPINF1, and TRPV2, were confirmed as differentially expressed after 6 h of exposure. To the best of our knowledge, this is the first large‐scale study reporting on potential gene expression modification associated with MMW radiation used in wireless communication applications. Bioelectromagnetics 33:147–158, 2012. © 2011 Wiley Periodicals, Inc.

[1]  Michael R. Green,et al.  Gene Expression , 1993, Progress in Gene Expression.

[2]  Y. Akyel,et al.  Current state and implications of research on biological effects of millimeter waves: a review of the literature. , 1998, Bioelectromagnetics.

[3]  M C Ziskin,et al.  Medical application of millimetre waves. , 1998, QJM : monthly journal of the Association of Physicians.

[4]  A Cowan,et al.  Suppression of pain sensation caused by millimeter waves: a double-blinded, cross-over, prospective human volunteer study. , 1999, Anesthesia and analgesia.

[5]  J. Winer,et al.  Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. , 1999, Analytical biochemistry.

[6]  Reilly Jp Comments concerning "Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields (up to 300 GHz)". , 1999 .

[7]  A Cowan,et al.  Pain relief caused by millimeter waves in mice: results of cold water tail flick tests. , 2000, International journal of radiation biology.

[8]  Alexis Agelan,et al.  Effect of millimeter waves on cyclophosphamide induced suppression of the immune system , 2002, Bioelectromagnetics.

[9]  M. Ziskin,et al.  Effect of millimeter waves on cyclophosphamide induced suppression of T cell functions , 2003, Bioelectromagnetics.

[10]  Thomas J. Prihoda,et al.  Micronuclei in Peripheral Blood and Bone Marrow Cells of Mice Exposed to 42 GHz Electromagnetic Millimeter Waves , 2004, Radiation research.

[11]  David Botstein,et al.  The role of heat shock transcription factor 1 in the genome-wide regulation of the mammalian heat shock response. , 2003, Molecular biology of the cell.

[12]  D. Kültz,et al.  Molecular and evolutionary basis of the cellular stress response. , 2005, Annual review of physiology.

[13]  Amerigo Beneduci,et al.  Frequency and irradiation time-dependant antiproliferative effect of low-power millimeter waves on RPMI 7932 human melanoma cell line. , 2005, Anticancer research.

[14]  E. Moros,et al.  The number of genes changing expression after chronic exposure to Code Division Multiple Access or Frequency DMA radiofrequency radiation does not exceed the false‐positive rate , 2006, Proteomics.

[15]  J P McNamee,et al.  Microarray Gene Expression Profiling of a Human Glioblastoma Cell Line Exposed In Vitro to a 1.9 GHz Pulse-Modulated Radiofrequency Field , 2006, Radiation research.

[16]  L. Le Coq,et al.  Interactions between 60-GHz millimeter waves and artificial biological membranes: dependence on radiation parameters , 2006, IEEE Transactions on Microwave Theory and Techniques.

[17]  E. Moros,et al.  Gene Expression does not Change Significantly in C3H 10T½ Cells after Exposure to 847.74 CDMA or 835.62 FDMA Radiofrequency Radiation , 2006, Radiation research.

[18]  L. Mcnaughton,et al.  The time-profile of the PBMC HSP70 response to in vitro heat shock appears temperature-dependent , 2007, Amino Acids.

[19]  Niels Kuster,et al.  Gene expression changes in human cells after exposure to mobile phone microwaves , 2006, Proteomics.

[20]  Catrin Bauréus Koch,et al.  Exposure of rat brain to 915 MHz GSM microwaves induces changes in gene expression but not double stranded DNA breaks or effects on chromatin conformation , 2006, Bioelectromagnetics.

[21]  Lingli Wang,et al.  Effects of Global System for Mobile Communications 1800 MHz radiofrequency electromagnetic fields on gene and protein expression in MCF‐7 cells , 2006, Proteomics.

[22]  M C Ziskin,et al.  Effect of cyclophosphamide and 61.22 GHz millimeter waves on T‐cell, B‐cell, and macrophage functions , 2006, Bioelectromagnetics.

[23]  Dariusz Leszczynski,et al.  Mobile phone radiation causes changes in gene and protein expression in human endothelial cell lines and the response seems to be genome‐ and proteome‐dependent , 2006, Proteomics.

[24]  Donald K Martin,et al.  An in vitro study of the effects of exposure to a GSM signal in two human cell lines: Monocytic U937 and neuroblastoma SK‐N‐SH , 2006, Cell biology international.

[25]  Andrew Williams,et al.  Analysis of gene expression in two human‐derived cell lines exposed in vitro to a 1.9 GHz pulse‐modulated radiofrequency field , 2007, Proteomics.

[26]  M Zhadobov,et al.  Low‐power millimeter wave radiations do not alter stress‐sensitive gene expression of chaperone proteins , 2007, Bioelectromagnetics.

[27]  Deqiang Lu,et al.  Studying gene expression profile of rat neuron exposed to 1800MHz radiofrequency electromagnetic fields with cDNA microassay. , 2007, Toxicology.

[28]  E. Perrotta,et al.  Antiproliferative effect of millimeter radiation on human erythromyeloid leukemia cell line K562 in culture: ultrastructural- and metabolic-induced changes. , 2007, Bioelectrochemistry.

[29]  N. Chemeris,et al.  Anti‐inflammatory effects of low‐intensity extremely high‐frequency electromagnetic radiation: Frequency and power dependence , 2008, Bioelectromagnetics.

[30]  A Cowan,et al.  Electromagnetic millimeter wave induced hypoalgesia: Frequency dependence and involvement of endogenous opioids , 2008, Bioelectromagnetics.

[31]  Ronan Sauleau,et al.  Absence of direct effect of low-power millimeter-wave radiation at 60.4 GHz on endoplasmic reticulum stress , 2009, Cell Biology and Toxicology.

[32]  P. A. Mason,et al.  Gene Expression Changes in the Skin of Rats Induced by Prolonged 35 GHz Millimeter-Wave Exposure , 2008, Radiation research.

[33]  Byoung-Tak Zhang,et al.  Characterization of biological effect of 1763 MHz radiofrequency exposure on auditory hair cells , 2008, International journal of radiation biology.

[34]  S. Alekseev,et al.  Numerical and Experimental Millimeter-Wave Dosimetry for In Vitro Experiments , 2008, IEEE Transactions on Microwave Theory and Techniques.

[35]  V. Romano Spica,et al.  No evidence of major transcriptional changes in the brain of mice exposed to 1800 MHz GSM signal , 2008, Bioelectromagnetics.

[36]  V. Chauhan,et al.  Radiofrequency Radiation and Gene/Protein Expression: A Review , 2009, Radiation research.

[37]  A. Beneduci Evaluation of the Potential In Vitro Antiproliferative Effects of Millimeter Waves at Some Therapeutic Frequencies on RPMI 7932 Human Skin Malignant Melanoma Cells , 2009, Cell Biochemistry and Biophysics.

[38]  Luciano Tarricone,et al.  The response of giant phospholipid vesicles to millimeter waves radiation. , 2009, Biochimica et biophysica acta.

[39]  R. Sauleau,et al.  Evaluation of the Potential Biological Effects of the 60-GHz Millimeter Waves Upon Human Cells , 2009, IEEE Transactions on Antennas and Propagation.

[40]  Ronan Sauleau,et al.  Study of narrow band millimeter‐wave potential interactions with endoplasmic reticulum stress sensor genes , 2009, Bioelectromagnetics.

[41]  Marvin C Ziskin,et al.  Millimeter wave effects on electrical responses of the sural nerve in vivo. , 2010, Bioelectromagnetics.

[42]  Masao Taki,et al.  Analysis of gene expression in a human-derived glial cell line exposed to 2.45 GHz continuous radiofrequency electromagnetic fields. , 2011, Journal of radiation research.

[43]  S. Lalléchère,et al.  Human keratinocytes in culture exhibit no response when exposed to short duration, low amplitude, high frequency (900 MHz) electromagnetic fields in a reverberation chamber , 2011, Bioelectromagnetics.

[44]  Ronan Sauleau,et al.  Millimeter-wave interactions with the human body: state of knowledge and recent advances , 2011, International Journal of Microwave and Wireless Technologies.