Genetic Damage in Mammalian Somatic Cells Exposed to Radiofrequency Radiation: A Meta-analysis of Data from 63 Publications (1990–2005)

Abstract Vijayalaxmi and Prihoda, T. J. Genetic Damage in Mammalian Somatic Cells Exposed to Radiofrequency Radiation: A Meta-analysis of Data from 63 Publications (1990–2005). Radiat. Res. 169, 561–574 (2008). During the last several decades, numerous researchers have examined the potential of in vitro and/or in vivo exposure of radiofrequency (RF) radiation to damage the genetic material in mammalian somatic cells. A meta-analysis of reported data was conducted to obtain a quantitative estimate (with 95% confidence intervals) of genotoxicity in RF-radiation-exposed cells compared with sham-exposed/unexposed control cells. The extent of genotoxicity was assessed for various end points, including single- and double-strand breaks in the DNA, incidence of chromosomal aberrations, micronuclei and sister chromatid exchanges. Among the several variables in the experimental protocols used in individual investigations, the influence of three specific variables related to RF-radiation exposure characteristics was examined in the meta-analysis: frequency, specific absorption rate, and exposure as continuous-wave, pulsed-wave and occupationally exposed/cell phone users. The overall data indicated that (1) the difference between RF-radiation-exposed and sham-/unexposed controls as well as the effect size or standardized mean difference due to RF-radiation exposure was small with very few exceptions; (2) at certain RF radiation exposure conditions, there were statistically significant increases in genotoxicity for some end points; and (3) the mean indices for chromosomal aberrations and micronuclei in RF-radiation-exposed and sham-/unexposed controls were within the spontaneous levels reported in the historical database. Considerable evidence for publication bias was found in the meta-analysis.

[1]  P. Boffetta,et al.  Chromosomal Aberrations in Lymphocytes of Healthy Subjects and Risk of Cancer , 2005, Environmental health perspectives.

[2]  J P McNamee,et al.  DNA Damage and Micronucleus Induction in Human Leukocytes after Acute In Vitro Exposure to a 1.9 GHz Continuous-Wave Radiofrequency Field , 2002, Radiation research.

[3]  P Boffetta,et al.  Chromosomal aberrations and SCEs as biomarkers of cancer risk. , 2006, Mutation research.

[4]  V. Garaj-Vrhovac,et al.  Comparison of chromosome aberration and micronucleus induction in human lymphocytes after occupational exposure to vinyl chloride monomer and microwave radiation. , 1990, Periodicum biologorum.

[5]  Mark W. Lipsey,et al.  Practical Meta-Analysis , 2000 .

[6]  P. Armitage,et al.  Controversies and achievements in clinical trials. , 1984, Controlled clinical trials.

[7]  E. Moros,et al.  Measurement of DNA Damage in Mammalian Cells Exposed In Vitro to Radiofrequency Fields at SARs of 3–5 W/kg , 2001, Radiation research.

[8]  Luc Verschaeve,et al.  Cytogenetic Effects of Microwaves from Mobile Communication Frequencies (954 Mhz) , 1995 .

[9]  Stefano Bonassi,et al.  Impact of Types of Lymphocyte Chromosomal Aberrations on Human Cancer Risk , 2004, Cancer Research.

[10]  G. Gandhi,et al.  Genetic damage in mobile phone users: some preliminary findings , 2005 .

[11]  Franz Adlkofer,et al.  Non-thermal DNA breakage by mobile-phone radiation (1800 MHz) in human fibroblasts and in transformed GFSH-R17 rat granulosa cells in vitro. , 2005, Mutation research.

[12]  M. Kirsch‐Volders,et al.  Human population studies with cytogenetic biomarkers: Review of the literature and future prospectives , 2005, Environmental and molecular mutagenesis.

[13]  G. Obe,et al.  Effects of high-frequency electromagnetic fields on human lymphocytes in vitro. , 1997, Mutation research.

[14]  S. Tsuda,et al.  The Comet Assay with Multiple Mouse Organs: Comparison of Comet Assay Results and Carcinogenicity with 208 Chemicals Selected from the IARC Monographs and U.S. NTP Carcinogenicity Database** , 2000, Critical reviews in toxicology.

[15]  J P McNamee,et al.  No Evidence for Genotoxic Effects from 24 h Exposure of Human Leukocytes to 1.9 GHz Radiofrequency Fields , 2003, Radiation research.

[16]  H. Lai,et al.  Melatonin and a spin-trap compound block radiofrequency electromagnetic radiation-induced DNA strand breaks in rat brain cells. , 1997, Bioelectromagnetics.

[17]  Kanako Wake,et al.  Effects of high frequency electromagnetic fields on micronucleus formation in CHO-K1 cells. , 2003, Mutation research.

[18]  B. Modlic,et al.  Investigation of the genotoxic effect of microwave irradiation in rat bone marrow cells: in vivo exposure. , 2004, Mutagenesis.

[19]  Martin L. Meltz,et al.  Primary DNA Damage in Human Blood Lymphocytes Exposed In Vitro to 2450 MHz Radiofrequency Radiation , 2000, Radiation research.

[20]  M. Meltz,et al.  Radiofrequency exposure and mammalian cell toxicity, genotoxicity, and transformation , 2003, Bioelectromagnetics.

[21]  D. Lloyd,et al.  The incidence of unstable chromosome aberrations in peripheral blood lymphocytes from unirradiated and occupationally exposed people. , 1980, Mutation research.

[22]  M. Meltz,et al.  Influence of radiofrequency radiation on chromosome aberrations in CHO cells and its interaction with DNA-damaging agents. , 1990, Radiation research.

[23]  W F Pickard,et al.  DNA damage in rat brain cells after in vivo exposure to 2450 MHz electromagnetic radiation and various methods of euthanasia. , 1998, Radiation research.

[24]  L. Verschaeve,et al.  Cytogenetic effects of 935.2-MHz (GSM) microwaves alone and in combination with mitomycin C. , 1997, Mutation research.

[25]  Olga Zeni,et al.  Genotoxic Effects of Amplitude-Modulated Microwaves on Human Lymphocytes Exposed in Vitro under Controlled Conditions , 1995 .

[26]  Robert A. Jones,et al.  DNA damage in Molt-4 T-lymphoblastoid cells exposed to cellular telephone radiofrequency fields in vitro , 1998 .

[27]  R. Painter A replication model for sister-chromatid exchange. , 1980, Mutation research.

[28]  H. Lai,et al.  Single- and double-strand DNA breaks in rat brain cells after acute exposure to radiofrequency electromagnetic radiation. , 1996, International journal of radiation biology.

[29]  S. Bonassi,et al.  Influence of sex on cytogenetic end points: evidence from a large human sample and review of the literature. , 1995, Cancer Epidemiology, Biomarkers and Prevention.

[30]  M. Fenech,et al.  The effect of donor age on spontaneous and induced micronuclei. , 1985, Mutation research.

[31]  A. Morley,et al.  Effect of Exposure to 900 MHz Radiofrequency Radiation on Intrachromosomal Recombination in pKZ1 Mice , 2001, Radiation research.

[32]  M. Fenech,et al.  HUman MicroNucleus project: international database comparison for results with the cytokinesis‐block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei , 2001, Environmental and molecular mutagenesis.

[33]  V. Garaj-Vrhovac,et al.  The effect of microwave radiation on the cell genome. , 1990, Mutation research.

[34]  K. Dickersin The existence of publication bias and risk factors for its occurrence. , 1990, JAMA.

[35]  Eduardo G Moros,et al.  Measurement of DNA Damage and Apoptosis in Molt-4 Cells after In Vitro Exposure to Radiofrequency Radiation , 2004, Radiation research.

[36]  J D Tucker,et al.  Cytogenetic end-points as biological dosimeters and predictors of risk in epidemiological studies. , 1997, IARC scientific publications.

[37]  Vijayalaxmi,et al.  Proliferation and cytogenetic studies in human blood lymphocytes exposed in vitro to 2450 MHz radiofrequency radiation. , 1997, International journal of radiation biology.

[38]  K J Johanson,et al.  Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. , 1984, Biochemical and biophysical research communications.

[39]  V. Garaj-Vrhovac,et al.  The correlation between the frequency of micronuclei and specific chromosome aberrations in human lymphocytes exposed to microwave radiation in vitro. , 1992, Mutation research.

[40]  L. Migliore,et al.  Induction of micronuclei in human lymphocytes exposed in vitro to microwave radiation. , 2000, Mutation research.

[41]  N. Singh,et al.  Modifications of alkaline microgel electrophoresis for sensitive detection of DNA damage. , 1994, International journal of radiation biology.

[42]  M D Shelby,et al.  Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. , 1988, Mutation research.

[43]  Cidambi Srinivasan,et al.  Combining Information: Statistical Issues and Opportunities for Research , 1993 .

[44]  D. McRee,et al.  Genotoxicity of radiofrequency signals. I. Investigation of DNA damage and micronuclei induction in cultured human blood cells , 2002, Bioelectromagnetics.

[45]  M. Taki,et al.  Effect of high-frequency electromagnetic fields with a wide range of SARs on chromosomal aberrations in murine m5S cells. , 2005, Mutation research.

[46]  S Sarkar,et al.  Effect of low power microwave on the mouse genome: a direct DNA analysis. , 1994, Mutation research.

[47]  Eduardo G. Moros,et al.  The Effect of 835.62 MHz FDMA or 847.74 MHz CDMA Modulated Radiofrequency Radiation on the Induction of Micronuclei in C3H 10T½ Cells , 2002, Radiation research.

[48]  S. Bonassi,et al.  Baseline Micronuclei Frequency in Children: Estimates from Meta- and Pooled Analyses , 2005, Environmental health perspectives.

[49]  V. Kašuba,et al.  Micronucleus induction after whole-body microwave irradiation of rats. , 2002, Mutation research.

[50]  Prabhjot Singh,et al.  Cytogenetic Damage in Mobile Phone Users: Preliminary Data , 2005 .

[51]  G. B. Gajda,et al.  DNA Damage in Human Leukocytes after Acute In Vitro Exposure to a 1.9 GHz Pulse-Modulated Radiofrequency Field , 2002, Radiation research.

[52]  L. Verschaeve,et al.  Cytogenetic investigations on microwaves emitted by a 455.7 MHz car phone. , 2000, Folia biologica.

[53]  G. Stephan,et al.  Chromosomal aberrations in peripheral lymphocytes from healthy subjects as detected in first cell division. , 1999, Mutation research.

[54]  Daniel V. Folkman,et al.  Reply to the comment on “Exposure of human peripheral blood lymphocytes to electromagnetic fields associated with cellular phones leads to chromosomal instability” , 2003, Bioelectromagnetics.

[55]  Vijayalaxmi,et al.  In vivo and in vitro effects of cigarette smoke on chromosomal damage and sister-chromatid exchange in human peripheral blood lymphocytes. , 1982, Mutation research.

[56]  John E. Hunter,et al.  Methods of Meta-Analysis: Correcting Error and Bias in Research Findings , 1991 .

[57]  V. Garaj-Vrhovac,et al.  Micronucleus assay and lymphocyte mitotic activity in risk assessment of occupational exposure to microwave radiation. , 1999, Chemosphere.

[58]  E. Moros,et al.  Micronuclei in the peripheral blood and bone marrow cells of rats exposed to 2450 MHz radiofrequency radiation , 2001, International journal of radiation biology.

[59]  M. J. Silva,et al.  Intra- and inter-laboratory variation in the scoring of micronuclei and nucleoplasmic bridges in binucleated human lymphocytes. Results of an international slide-scoring exercise by the HUMN project. , 2003, Mutation research.

[60]  O. Garson,et al.  A chromosomal study of workers with long‐term exposure to radio‐frequency radiation , 1991, The Medical journal of Australia.

[61]  Eduardo G. Moros,et al.  Cytogenetic Studies in Human Blood Lymphocytes Exposed In Vitro to Radiofrequency Radiation at a Cellular Telephone Frequency (835.62 MHz, FDMA) , 2001, Radiation research.

[62]  M. Bender,et al.  Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. II. Extension of age range. , 1989, Mutation research.

[63]  Vijayalaxmi,et al.  Assessment of radiation-induced DNA damage in human blood lymphocytes using the single-cell gel electrophoresis technique. , 1992, Mutation research.

[64]  R. Tice,et al.  A simple technique for quantitation of low levels of DNA damage in individual cells. , 1988, Experimental cell research.

[65]  Xiao-Hua Zhou,et al.  Statistical Methods for Meta‐Analysis , 2008 .

[66]  M. Bender,et al.  On the distribution of spontaneous SCE in human peripheral blood lymphocytes. , 1992, Mutation research.

[67]  C De Wagter,et al.  In vitro cytogenetic effects of 2450 MHz waves on human peripheral blood lymphocytes. , 1993, Bioelectromagnetics.

[68]  M. Meltz,et al.  Absence of a synergistic effect between moderate-power radio-frequency electromagnetic radiation and adriamycin on cell-cycle progression and sister-chromatid exchange. , 1991, Bioelectromagnetics.

[69]  Valentina Maggini,et al.  Individual responsiveness to induction of micronuclei in human lymphocytes after exposure in vitro to 1800-MHz microwave radiation. , 2005, Mutation research.

[70]  Eduardo G. Moros,et al.  Chromosome Damage and Micronucleus Formation in Human Blood Lymphocytes Exposed In Vitro to Radiofrequency Radiation at a Cellular Telephone Frequency (847.74 MHz, CDMA) , 2001, Radiation research.

[71]  Ji-liang He,et al.  Study of low-intensity 2450-MHz microwave exposure enhancing the genotoxic effects of mitomycin C using micronucleus test and comet assay in vitro. , 2002, Biomedical and environmental sciences : BES.

[72]  Eli Jerby,et al.  Exposure of human peripheral blood lymphocytes to electromagnetic fields associated with cellular phones leads to chromosomal instability , 2003 .

[73]  Italy,et al.  Age-related increase of baseline frequencies of sister chromatid exchanges, chromosome aberrations, and micronuclei in human lymphocytes. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[74]  P. Schmezer,et al.  The effect of various antioxidants and other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the COMET assay. , 1994, Mutation research.

[75]  L. Verschaeve,et al.  Genetic effects of radiofrequency radiation (RFR). , 2005, Toxicology and applied pharmacology.

[76]  V. Garaj-Vrhovac,et al.  The relationship between colony-forming ability, chromosome aberrations and incidence of micronuclei in V79 Chinese hamster cells exposed to microwave radiation. , 1991, Mutation research.

[77]  N. Kuster,et al.  Effects of 1-Week and 6-Week Exposure to GSM/DCS Radiofrequency Radiation on Micronucleus Formation in B6C3F1 Mice , 2005, Radiation research.

[78]  E. Moros,et al.  Measurements of Alkali-Labile DNA Damage and Protein–DNA Crosslinks after 2450 MHz Microwave and Low-Dose Gamma Irradiation In Vitro , 2004, Radiation research.

[79]  L. Verschaeve,et al.  Cytogenetic effects of 900 MHz (GSM) microwaves on human lymphocytes. , 2001, Bioelectromagnetics.

[80]  M. Taki,et al.  Effects of 2.45-GHz Electromagnetic Fields with a Wide Range of SARs on Micronucleus Formation in CHO-K1 Cells , 2004, TheScientificWorldJournal.

[81]  R E Durand,et al.  Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the "comet" assay. , 1990, Radiation research.

[82]  J. Ioannidis,et al.  Quantitative Synthesis in Systematic Reviews , 1997, Annals of Internal Medicine.

[83]  L. Verschaeve,et al.  954 MHz microwaves enhance the mutagenic properties of mitomycin C , 1996, Environmental and molecular mutagenesis.

[84]  The rate of elimination of chromosomal aberrations after accidental exposure to microwave radiation , 1993 .

[85]  P. A. Mason,et al.  Radio frequency electromagnetic fields: Cancer, mutagenesis, and genotoxicity , 2003, Bioelectromagnetics.

[86]  W F Pickard,et al.  Measurement of DNA damage after exposure to 2450 MHz electromagnetic radiation. , 1997, Radiation research.

[87]  H. Lai,et al.  Acute low-intensity microwave exposure increases DNA single-strand breaks in rat brain cells. , 1995, Bioelectromagnetics.

[88]  Guenter Obe,et al.  Controversial Cytogenetic Observations in Mammalian Somatic Cells Exposed to Radiofrequency Radiation , 2004, Radiation research.

[89]  H. Norppa,et al.  Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). , 1998, Cancer research.

[90]  L. E. Anderson,et al.  Genotoxic Potential of 1.6 GHz Wireless Communication Signal: In Vivo Two-Year Bioassay , 2003, Radiation research.

[91]  Lu Deqiang,et al.  Studying the synergistic damage effects induced by 1.8 GHz radiofrequency field radiation (RFR) with four chemical mutagens on human lymphocyte DNA using comet assay in vitro. , 2005, Mutation research.

[92]  V. Garaj-Vrhovac,et al.  X-rays, microwaves and vinyl chloride monomer: their clastogenic and aneugenic activity, using the micronucleus assay on human lymphocytes. , 1992, Mutation research.

[93]  M. Scarfì,et al.  Evaluation of genotoxic effects in human peripheral blood leukocytes following an acute in vitro exposure to 900 MHz radiofrequency fields , 2005, Bioelectromagnetics.

[94]  国際非電離放射線防護委員会 ICNIRP statement on the "Guidelines for limiting exposure to time-varying electric, magnetic, and electromagnetic fields (up to 300 GHz)". , 2009, Health physics.

[95]  H. Lalić,et al.  Comparison of chromosome aberrations in peripheral blood lymphocytes from people occupationally exposed to ionizing and radiofrequency radiation. , 2001, Acta medica Okayama.

[96]  Vijayalaxmi,et al.  Comments on: "DNA strand breaks" by Diem et al. [Mutat. Res. 583 (2005) 178-183] and Ivancsits et al. [Mutat. Res. 583 (2005) 184-188]. , 2006, Mutation research.

[97]  A. Sannino,et al.  Lack of Genotoxic Effects (Micronucleus Induction) in Human Lymphocytes Exposed In Vitro to 900 MHz Electromagnetic Fields , 2003, Radiation research.

[98]  P. K. Gadhia,et al.  A Preliminary Study to Assess Possible Chromosomal Damage Among Users of Digital Mobile Phones , 2003 .

[99]  Vijayalaxmi Cytogenetic Studies in Human Blood Lymphocytes Exposed In Vitro to 2.45 GHz or 8.2 GHz Radiofrequency Radiation , 2006, Radiation research.

[100]  Vijayalaxmi,et al.  Frequency of micronuclei in the peripheral blood and bone marrow of cancer-prone mice chronically exposed to 2450 MHz radiofrequency radiation. , 1997, Radiation research.

[101]  M. Fenech,et al.  An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. , 2006, Carcinogenesis.

[102]  W F Pickard,et al.  Measurement of DNA damage after acute exposure to pulsed‐wave 2450 MHz microwaves in rat brain cells by two alkaline comet assay methods , 2004, International journal of radiation biology.

[103]  Guglielmo d'Ambrosio,et al.  Cytogenetic damage in human lymphocytes following GMSK phase modulated microwave exposure , 2002, Bioelectromagnetics.

[104]  W F Pickard,et al.  Measurement of DNA damage after exposure to electromagnetic radiation in the cellular phone communication frequency band (835.62 and 847.74 MHz). , 1997, Radiation research.