Research - Toxicological

Cancer studies include those involving cell proliferation, ornithine decarboxylase (ODC), genotoxicity, and tumour growth and development.

Cell proliferation: The Independent Expert Group on Mobile Phones comments: "Changes in the kinetics of cell division and in the proliferation of cells play a crucial role in the generation of cancer". Several studies have examined the relationship between RF radiation, in the mobile phone frequencies, and cell proliferation. Cleary et al. (1990a, 1990b, 1995) have reported increased cell proliferation in experiments using brain glioma cells, human lymphocytes, and hamster ovary cells. The SARs were high in these studies, but temperature levels were well controlled. Donnellan (1997) also found changes in cell proliferation when mast cells were exposed to 835 MHz under athermal conditions. Kwee and Raskmark (1998), however, found a decrease in cell growth of human epithelial amnion cells exposed to 960 MHz microwave fields, and Capri (2004b) also found a slight decrease in cell proliferation after exposure to 900 MHz RFR. On the other hand Stagg (1997) and Vijayalaxmi (1997) found no increase in cell proliferation in their studies using 836.55 MHz and 2450 MHz respectively. Similarly, Zeni (2003) found no change in cell cycle kinetics when lymphocytes were exposed to various signals at 900 MHz frequency. Scarfi (2006), in a two-laboratory study, found no changes in cell proliferation in lymphocytes exposed to RFR at 900 MHz. Byus (1984) and Paulraj (2002) have reported decreased protein kinase activity in rats following exposure to RF radiation. Byus used modulated fields, while Paulraj used continuous wave radiation. Protein kinase plays a role in signal transduction for a variety of substances that activate cellular function and proliferation. Pacini (2002) reported that exposure of skin fibroblasts to 900 MHz RF radiation for 1 hour altered gene expression, proliferation, and morphology.

Ornithine decarboxylase: ODC is the initial enzyme involved in the production of polyamines, which in turn are involved in the growth of normal and cancer cells. The report by the Expert Panel of the Royal Society of Canada (1999) extensively reviewed the relationship between relationship between ODC activity and cancer. It pointed out that ODC activity may be increased in pre-malignant conditions, or following exposure to chemical carcinogens or known oncogenes, and that ODC may function as an oncogenic protein at high levels of activity. The relationship between electromagnetic radiation and ODC activity was also reviewed in the RSC Report. Several studies have shown increased ODC levels after EMF exposure (Byus, 1997, Paulraj, 2002). Desta (2003), however, showed a decrease in ODC levels with exposure to RFR at 835 MHz, but only at SAR levels above 5W/kg. These levels were associated with temperature increase in the medium used. Höytö (2006) also showed decreased ODC levels after RFR, but only in primary astrocytes and not in secondary neural cell lines. The same group (Höytö, 2007) found no increase in ODC activity on murine fibroblasts exposed at 835 or 872 MHz at SARs of 2.5 and 6.0 W/kg. The Independent Expert Group on Mobile Phones (2000), however, stated in its review:

" In general, the studies reported modest increases in ODC activity only at modulation frequencies of about 10-60 Hz. DNA synthesis, which would increase a proliferative response to raised ODC activity, was not subsequently increased". The Expert Group also pointed out that the maximum increase in ODC activity produced by amplitude-modulated RF radiation (approximately a doubling) is much less than that elicited by known tumour-producing substances, which can cause up to 500-fold changes in ODC activity in relevant tissues". The Group concluded: "…it is very unlikely that these small changes could, on their own, have a tumour-promoting effect. It is also unlikely that such effects act synergistically with other environmental hazards and contribute to tumour promotion".

Genotoxicity: It is thought that the cancer process is started by changes in the genetic material (or DNA) of cells. These changes are called genotoxic effects. Many studies have been done on these effects in the laboratory. The in vivo experiments by Lai and Singh (1995,1996) merit special mention, in view of the wide attention they have received. These authors reported an increase in DNA strand breaks in the brain cells of rats exposed for two hours to pulsed or continuous-wave 2450 MHz RF fields at averaged whole body SARs of 0.6 and 1.2 W/kg. In another study in 1997, they investigated whether free radicals play a role in this effect and they found that melatonin, and another compound known to be a free radical scavenger, blocked the RF effect of increased DNA strand breaks. These authors have also reported that a temporally incoherent magnetic field (noise) blocked microwave-induced increases in DNA strand breaks (Lai and Singh, 2005). These results have not been replicated, to date, by other scientists using similar experimental conditions.Diem (2005), however, reported that exposure to 1800 MHz RFR was associated with DNA strand breaks in human and rat cells. Malyapa (1997 a, b) could not replicate Lai and Singh's results at 2450 MHz or at a frequency of 835/847 MHz. Lagroye (2004 b), using methods identical to those of Lai and Singh, could find no evidence that pulsed-wave 2450 MHz microwaves produced DNA damage in rat brain cells. Hossmann and Hermann (2003) suggest that the experiments by Lai and Singh used peak power that was much higher than the mean power, which may have accounted for the observed DNA damage. Vijayalaxmi (2003) found no evidence of genotoxicity in rats exposed for 2 years to near-field RF exposure.

In vitro studies in general have failed to show evidence of DNA damage (Malyapa 1997a,b; Vijayalaxmi 2000, 2001, 2006; Gos, 2000; Roti Roti, 2001; Maes, 2001, Lagroye, 2004a, Hook, 2004, Zeni, 2005, Sakuma, 2006, Stronati, 2006)). One paper showed a reduction in the frequency of recombination events in mice exposed to RF radiation (Sykes, 2001). This is seen with various genotoxic agents, so may not be a beneficial outcome. However, Tice et al. (2002) found an increased frequency of micronucleated lymphocytes exposed to different RF signals for 24 hours at an average SAR of 5.0 W/kg or 10 W/kg. Micronuclei arise from chromosomal damage. Others have found an increased frequency of micronucleated cells following exposure to RF signals (Garaj-Vrhovac, 1991; Maes, 1995; d'Ambrosio 2002; Trosic 2002). Zotti-Martelli (2005) also found an increase in micronuclei in lymphocytes exposed to 1800 Mhz at different power densities and for different time periods, but also found a wide inter-individual variability in the response. However, Vijayalaxmi (2001, 2006) Bisht (2002) and McNamee (2002 a,b; 2003), Zeni (2003), Gorlitz (2005), Scarfi (2006) and Juutilainen (2007) did not find an icrease in micronucleated cells after RFR exposure. Balcer-Kubiczek and Harrison (1989,1991) showed increased cell transformation when C3H/10T½ cells were exposed to 2450 MHz RF fields and also to a known tumour promoter (TPA). Microwaves alone had no effect. " Cell transformation is one step along the way to malignancy and involves the release of cells from contact inhibition so that cell growth continues despite the close proximity of other cells" (Royal Society of Canada, 1999). Another group found evidence of chromosomal instability in human blood lymphocytes exposed to RF radiation (Mashevich, 2003) and Gadhia (2003) reported a significant increase in chromosome abnormalities in blood cells of users of mobile phones. Zhang (2002) found that when exposure of lymphocytes to 2450 MHz microwaves for 2 hours preceded exposure to Mitomycin C, there was evidence of a synergistic effect. DNA damage, estimated by the comet assay, was increased compared to that seen with Mitomycin C alone, although the number of micronucleated cells was not increased. Whitehead (2005) failed to confirm the results of Goswami (1999) that RFR exposure increased levels of the proto-oncogene Fos. Baohong (2005) also found a synergistic effect of RFR, at 1.8 GHz frequency and SAR of 3 W/kg, and Mitomycin-C, using the comet assay. These authors also found synergy between RFR and 4-nitroquinoline-1-oxide. Chang (2005) did not find evidence of genotoxicity in bacterial cultures exposed to 835 MHz RFR at a SAR of 4 W/kg for 48 hours.

Gene expression: There have been a limited number of studies that have examined the effect of RFR on the expression of genes, which can be an indicator of genotoxicity. Fos is proto-oncogene that is one of the immediate early genes (IEG) that are rapidly and transiently induced in response to external stimuli. Their protein products mediate long-term changes in neuronal activity. The IEG response is a useful indicator of cells undergoing stress in the central nervous system (Finnie, 2005). Whitehead (2005) failed to confirm the results of Goswami (1999) that RFR exposure increased levels of Fos, although the SAR levels employed were very different. Finnie (2005) found that Fos levels were similar in mice exposed to RFR and sham-exposed controls, but both groups had much higher levels than those in freely-moving controls. This suggested that the majority of the gene expression response was due to immobilization rather than irradiation. Lee (2005) exposed human HL-60 cells to RFR at 2.45 GHz frequency and a SAR of 10 W/kg, and found in a series analysis of gene expression that a large number of genes altered their expression after 2 and 6 hours of irradiation. Chauhan (2006) found that exposure of human lymphoblasoma cells to RFR at SARs of 1 and 10 W/kg had no effect on the expression of proto-oncogenes FOS, JUN, and MYC and the same group found no effect on the levels of these proto-oncogenes when other human cell lines were exposed to RFR at similar SARs (Chauhan, 2006B). Belyaev (2006) reported that rats exposed to RFR at 915 MHz frequency showed some evidence of disturbed gene expression in cerebellum cells. Out of 8800 genes tested, 11 showed upregulation in a range of 1.34-2.74 fold, and one gene was downregulated 0.48 fold. The authors pointed out that these changes could be related to chance because of the number of gene arrays, and could also be due to the fact that the brain normally shows small changes in gene expression. In contrast, Whitehead (2006a,b), Qutob (2006), Hirose (2006) and Zeng (2006) found RFR at different frequencies had no effect on gene expression. Whitehead (2006b) emphasized that there is a high chance of false positives because of the large number of genes tested. They point out that it is important to use repeated RF exposures with matched shams, a sham versus sham analysis, and a comparison to a matched control.

The UK Independent Expert Group on Mobile Phones summarized the situation as follows:

"The balance of evidence, from both in vitro and in vivo experiments, indicates that neither acute nor chronic exposure to RF fields increased mutation or chromosomal aberration frequencies when temperatures are maintained within physiological limits (UNEP/WHO/IRPA, 1993). This suggests that RF exposure is unlikely to act as a tumour initiator."

The Royal Society of Canada Expert Panel Report concludes

"a large number of laboratory studies of the potential health effects of radiofrequency fields have focused on genotoxicity, including studies of tumorigenesis, promotion, progression, altered cell proliferation, and DNA damage. The great majority of these studies have failed to demonstrate genotoxic effects due to exposure to radiofrequency fields" (page 75).

Other reviews by Verschaeve (1995), Brusick (1998), and Verschaeve and Maes (1998) came to the same general conclusion. Meltz (2003) carried out a detailed review, and his conclusions are worth quoting at length because they address some of the inconsistencies in the results of studies:

"There is an abundance of evidence that RF exposures at various frequencies and modulations at SAR levels that do not result in exposing cells at elevated temperatures over time, do not cause a wide range of different types of genotoxic damage. The measures of genotoxic damage that are absent after RF exposures, by the weight of the evidence, include the induction of DNA SSBs or DSBs (single or double strand breaks), the induction of chromosomal aberrations, and the induction of SCEs (sister chromatid exchanges).

There is limited evidence that RF exposure, using some exposure systems, results in the induction of micronuclei; considerable other evidence exists that this does not occur. The induction of micronuclei is not consistent with the demonstrated absence of chromosome aberrations and DNA strand breaks.

There is limited evidence that RF exposure does not result in cancer-like changes in cells, as measures by the technique of in vitro cell transformation. There is no evidence contradicting this observation."

Some of the important laboratory studies dealing with genotoxicity are listed below.

Authors
Baohong W, Jiliang H, Lifen J, Deqiang L, et al.
Title
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.
Journal
Mutat Res 2005;578:149-157.
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Authors
Belyaev IY, Koch CB, Terenius O, Roxstrom-Lindquist K, et al.
Title
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.
Journal
Bioelectromagnetics 2006;27:295-306.
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Authors
Belyaev IY, Markovà E, Hillert L, Malmgren LOG, Persson BRR.
Title
Microwaves from UMTS/GSM mobile phones induce long-lasting inhibition of 53BP1/-H2AX DNA repair foci in human lymphocytes (p n/a).
Journal
Bioelectromagnetics Ahead of print Oct 6 2008. DOI 10.1002/bem.20445.

Authors
Bisht KS, Moros EG, Straube WL, Baty JD, Roti Roti JL
Title
The effect of 835.62 MHz FDMA or 847.74 MHz CDMA modulated radiofrequency radiation on the induction of micronuclei in C3H 10T½ cells.
Journal
Radiation Research 157:506-515
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Authors:
Capri M, Scarcella E, Fumelli C, Bianchi E, et al. (2004b)
Title:
In vitro exposure of human lymphocytes to 900 MHz CW and GSM modulated radiofrequency: studies of proliferation, apoptosis and mitochondrial membrane potential.
Journal:
Radiation Research 162:211-218.
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Authors
Chang S-K, Choi J-S, Gil H-W, Yang J-O, et al.
Title
Genotoxicity evaluation of electromagnetic fields generated by 835-MHz mobile phone frequency band.
Journal
Eur J Cancer Prev 2005;14:175-179.
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Authors
Chauhan V, Mariampillai A, Bellier PV, Qutob SS, et al.
Title
Gene expression analysis of a human lymphoblastoma cell line exposed in vitro to an intermittent 1.9 GHz pulse-modulated radiofrequency field.
Journal
Radiat Res 2006a;165:424-429.
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Authors
Chauhan V, Mariampillai A, Gajda GB, Thansandote A, et al.
Title
Analysis of proto-oncogene and heat-shock protein gene expression in human derived cell-lines exposed in vitro to an intermittent 1.9 GHz pulse-modulated radiofrequency field.
Journal
Int J Radiat Biol 2006b;82:347-354.
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Authors
Chauhan V, Qutob SS, Lui S, Mariampillai A, Bellier PV, Yauk CL, Douglas GR, Williams A, McNamee JP
Title
Analysis of gene expression in two human-derived cell lines exposed in vitro to a 1.9 GHz pulse-modulated radiofrequency field.
Journal
Proteomics 2007a;7(21):3896-3905.

Authors
D'Ambrosio G, Massa R, Scarfi MR, Zeni O
Title
Cytogenetic damage in human lymphocytes following GMSK phase modulated microwave exposure.
Journal
Bioelectromagnetics 2002;23:7-13.
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Authors
Desta, A. B., Owen RD, Cress LW.
Title
Non-thermal exposure to radiofrequency energy from digital wireless phones does not affect ornithine decarboxylase activity in L929 cells.
Journal
Radiat.Res. 2003;160:488-491.
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Authors
Diem E, Schwarz C, Adlkofer F, Jahn O, et al.
Title
Non-thermal DNA breakage by mobile-phone radiation (1800 MHz) in human fibroblasts and in transformed GFSH-R17 rat granulosa cells in vitro.
Journal
Mutat Res 2005;583:178-183.
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Author
Finnie JW.
Title
Expression of the immediate early gene, c-fos, in mouse brain after acute global system for mobile communication microwave exposure.
Journal
Pathology 2005;37:231-3.
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Authors
Gadhia PK, Shah T, Mistry A, Pithawala M, et al.
Title
A preliminary study to assess possible chromosomal damage among users of digital mobile phones
Journal
Electromagnetic Biology and Medicine 2003;22:149-159.
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Authors
Gorlitz B-D, Muller M, Ebert S, Hecker H, et al.
Title
Effects of 1-week and 6-week exposure to GSM/DCS radiofrequency radiation on micronucleus formation in B6C3F1 mice.
Journal
Radiation Research 2005;164:431-439.
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Authors
Gos P, Eicher B, Kohli J, Heyer W-D
Title
No mutagenic or recombinogenic effects of mobile phone fields at 900 MHz detected in the yeast Saccharomyces cerevisiae.
Journal
Bioelectromagnetics 2000;21:515-523.
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Authors
Hirose H, Sakuma N, Kaji N, Suhara T, et al.
Title
Phosphorylation and gene expression of p53 are not affected in human cells exposed to 2.1425 GHz band CW or W-CDMA modulated radiation allocated to mobile hone radio base stations.
Journal
Bioelectromagnetics 2006;27:494-504.
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Authors
Höytö A, Juutilainen J, Naarala J
Title
Ornithine decarboxylase activity is affected in primary astrocytes but not in secondary cell lines exposed to 872 MHz RF radiation.
Journal
Int J Radiat Biol 2006;83:367-374.
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Authors
Höytö A, Juutilainen J, Naarala L.
Title
Ornithine decarboxylase activity of L929 cells after exposure to continuous wave or 50 Hz modulated radiofrequency radiation - a replication study.
Journal
Bioelectromagnetics 2007;28:501-508.
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Authors
Hook G, Zhang P, Lagroye I, Higashikubo R, et al.
Title
Measurement of DNA damage and apoptosis in Molt-4 cells after in vitro exposure to radiofrequency radiation
Journal
Radiat Res 2004;161:193-200.
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Authors
Hruby R, Neubauer G, Kuster N, Frauscher M.
Title
Study on potential effects of “902-MHz GSM-type Wireless Communication Signals” on DMBA-induced mammary tumours in Sprague–Dawley rats.
Journal
Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2008;649(1-2):34-44.

Authors
Huang TQ, Lee MS, Oh EH, Kalinec F, Zhang BT, Seo JS, Park WY.
Title
Characterization of biological effect of 1763 MHz radiofrequency exposure on auditory hair cells.
Journal
Int J Radiat Biol 2008;84(11): 909-915.

Authors
Juutilainen J, Heikkinen P, Soikkeli H, Maki-Paakkanen J.
Title
Micronucleus frequency in erythrocytes of mice after long-term exposure to radiofrequency radiation.
Journal
Int J Radiat Biol 2007, 83:213-220.
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Authors
Khurana, Vini G.
Title
Cell Phone and DNA Story Overlooked Studies
Journal
Science 28 November 2008 322(5906):1325 DOI: 10.1126/science.322.5906.1325a

Authors
Kim TH, Huang TQ, Jang JJ, Kim MH, Kim HJ, Lee JS, Pack JK, Seo JS, Park WY.
Title
Local exposure of 849 MHz and 1763 MHz radiofrequency radiation to mouse heads does not induce cell death or cell proliferation in brain.
Journal
Exp Mol Med. 2008 Jun 30;40(3):294-303.

Authors
Lagroye I, Hook GJ, Wettring BA, Baty JD, et al.
Title
Measurements of alkali-labile DNA damage and protein-DNA crosslinks after 2450 MHz microwave and low-dose gamma irradiation in vitro.
Journal
Radiat Res 2004 (a);161:201-214.
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Authors
Lagroye, Anane R, Wettring BA, Moros EG, et al.
Title
Measurements of DNA damage after acute exposure to pulsed-wave 2450 MHz microwaves in rat brain cells by two alkaline comet assay methods.
Journal
Int J Radiat Biol 2004 (b);80:11-20.
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Authors
Lai H, Singh NP
Title
Acute low-intensity microwave exposure increases DNA single strand breaks in rat brain

Jurnal
Bioelectromagnetics 1995;16:207-210.
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Authors
Lai H, Singh NP
Title
Single- and double-strand DNA breaks in rat brain cells after acute exposure to radiofrequency electromagnetic radiation.
Journal
Int J Radiation Biol 1996;69:513-521.
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Authors
Lai H, Singh NP
Title
Melatonin and a spin-trap compound block radiofrequency electromagnetic radiation-induced DNA strand breaks in rat brain cells.
Journal
Bioelectromagnetics 1997;18:446-454.
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Authors
Lai H, Singh NP.
Title
Interaction of microwaves and a temporally incoherent magnetic field on single and double DNA strand breaks in rat brain cells.
Journal
Electromagnetic Biology and Medicine. 2004;24:23-29.
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Authors
Lee S, Johnson D, Dunbar K, Dong H, et al.
Title
2.45 GHz radiofrequency fields alter gene expression in cultured human cells.
Journal
FEBS Letters 2005;579:4829-4836.
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Authors
Li l, Bisht KS, LaGroye I, Zhang P, et al.
Title
Measurement of DNA damage in mammalian cells exposed in vitro to radiofrequency fields at SARs of 3-5 W/kg
Journal
Radiation Research 2001;156:328-332.
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Author
Lin JC
Title
Tumor incidence studies in lymphoma-prone mice exposed to GSM mobile-phone radiation.
Journal
Radio Sci Bull 2008;324;41-44.

Authors
Maes A, Collier M, Verschaeve L
Title
Cytogenetic effects of 900 MHz (GSM) microwaves on human lymphocytes.
Journal
Bioelectromagnetics 2001;22:91-96.
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Authors
Maes A, Collier M, Verschaeve L.
Title
Cytogenetic investigations on microwaves emitted by a 455.7 MHz car phone.
Journal
Folia Biologica (Praha) 2000;46:175-180.
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Authors
Malyapa RS, Ahern EW, Straube WL, et al.
Title
Measurement of DNA damage after exposure to 2450 MHz electromagnetic radiation.
Journal
Radiat Res1997;148:608-617.
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Authors
Malyapa RS, Ahern EW, Straube WL, et al.
Title
Measurement of DNA damage after exposure to electromagnetic radiation in the cellular communications frequency band (835.62 and 847.74 MHz).
Journal
Radiat Res 1997;148:618-627.
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Authors
Malyapa RS, Ahern EW, Chen B, et al.
Title
DNA damage in rat brain cells after in vivo exposure to 2450 MHz electromagnetic radiation and various methods of euthanasia.
Journal
Radiat Res1998;149:637-645.
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Authors
Mashevich M, Folkman D, Kesar A, Barbul A, et al.
Title
Exposure of human peripheral blood lymphocytes to electromagnetic fields associated with cellular phones leads to chromosomal instability.
Journal
Bioelectromagnetics 2003;24:82-90.
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Authors
McNamee JP, Bellier PV, Gajda GB, Miller SM, et al.
Title
DNA damage and micronucleus induction in human leukocytes after acute in vitro exposure to a 1.9 GHz continuous-wave radiofrequency field.
Journal
Radiat Res 2002;158:523-533.
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Authors
McNamee JP, Bellier PV, Gajda GB, Lavallee BF, et al.
Title
DNA damage in human leukocytes after acute in vitro exposure to a 1.9 GHz pulse-modulated radiofrequency field.
Journal
Radiat Res 2002;158:534-537.
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Authors
McNamee JP, Bellier PV, Gajda GB, Lavallée BF, et al.
Title
No evidence for genotoxic effects from 24 hr exposure of human leukocytes to 1.9 GHz radiofrequency fields.
Journal
Radiat Res 2003;159:693-697.
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Authors
Pacini S, Ruggiero M, Sardi I, Aterini S, et al.
Title
Exposure to global system for mobile communication (GSM) cellular phone radiofrequency alters gene expression, proliferation, and morphology of human skin fibroblasts.
Journal
Oncol Res 2002;13:19-24.
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Authors
Paulraj R, Behari J.
Title
The effect of low-level continuous 2.45 GHz waves on enzymes of the developing rat brain.
Journal
Electro-Magnetobiol 2002;21:221-231
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Authors
Paparini A, Rossi P, Gianfranceschi G, Brugaletta V, Falsaperla R, De Luca P, Romano Spica V.
Title
No evidence of major transcriptional changes in the brain of mice exposed to 1800 MHz GSM signal
Journal
Bioelectromagnetics 2008;29(4);312-323.

Authors
Qutob SS, Chauhan V, Yauk CL, Douglas GR, et al.
Title
Microarray gene expression profiling of a human glioblastoma cell line exposed in vitro to a 1.9 GHz pulse-modulated radiofrequency field.
Journal
Radiat Res 2006;165:636-644.
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Authors
Roti Roti JL, Malyapa RS, Bisht KS, Ahern EW, et al.
Title
Neoplastic transformation in C3H 10T1/2 cells after exposure to 835.62 MHz FDMA and 847.74 MHz CDMA radiations.
Journal
Radiat Res 2001;155:239-247.
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Authors
Sakuma N, Komatsubara Y, Takeda H, Hirose H, et al.
Title
DNA strand breaks are not induced in human cells exposed to 2.1425 GHz band CW and W-CDMA modulated radiofrequency fields allocated to mobile radio base stations.
Journal
Bioelectromagnetics 2006;27:51-57.
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Authors
Scarfi MR, Fresegna AM, Villani P, Pinto R, et al.
Title
Exposure to radiofrequency radiation (900 MHz, GSM signal) does not affect micronucleus frequency and cell proliferation in human peripheral blood lymphocytes: an interlaboratory study.
Journal
Radiat Res 2006;165:655-663.
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Authors
Stronati L, Testa A, Moquet J, Edwards A, et al.
Title
935 MHz cellular phone radiation. An in vitro study of genotoxicity in human lymphocytes.
Journal
Int J Radiat Biol 2006;82:339-346
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Authors
Sykes PJ, McCallum BD, Hooker AM
Title
Effect of exposure to 900 MHz radiofrequency radiation on intrachromosomal recombination in pKZ1 mice.
Journal
Radiation Research 2001;156:495-502.
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Authors
Tice RR, Hook GG, Donner M, McRee DI, et al.
Title
Genotoxicity of radiofrequency signals. 1. Investigation of DNA damage and micronuclei induction in cultured human blood cells.
Journal
Bioelectromagnetics 2002;23:113-126.
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Authors
Trosic I, Busljeta I, Kasuba V, Rozgaj R
Title
Micronucleus induction after whole-body radiation of rats.
Journal
Mutation Research 2002;521:73-79.
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Authors
Valbonesi P, Franzellitti S, Piano A, Contin A, Biondi C, Fabbri E.
Title
Evaluation of HSP70 Expression and DNA Damage in Cells of a Human Trophoblast Cell Line Exposed to 1.8 GHz Amplitude-Modulated Radiofrequency Fields.
Journal
Radiat. Res. 2008;169:270-279.

Authors
Vanderstraeten J, Verschaeve L.
Title
Gene and protein expression following exposure to radiofrequency fields from mobile phones.
Journal
Environ Health Perspect (2008);116:1131-1135.

Author
Vogel G
Title
SCIENTIFIC MISCONDUCT: Fraud Charges Cast Doubt on Claims of DNA Damage From Cell Phone Fields
Journal
Science (2008);321(5893):1144 – 1145.

Authors
Vijayalaxmi, Leal BZ, Szilagyi M, Prihoda TJ, et al.
Title
Primary DNA damage in human blood lymphocytes exposed in vitro to 2450 MHz radiofrequency radiation.
Journal
Radiat Res 2000;153:479-486.
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Authors
Vijayalaxmi, Pickard WF, Bisht KS, Leal BZ, et al.
Title
Cytogenetic studies in human blood lymphocytes exposed in vitro to radiofrequency radiation at a cellular telephone frequency (835.62 MHz, FDMA).
Journal
Radiat Res 2001;155:113-121.
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Authors
Vijayalaxmi, Bisht KS, Pickard WE, Meltz ML, Roti Roti JL, et al. (2001)
Title
Chromosome damage and micronucleus formation in human blood lymphocytes exposed in vitro to radiofrequency radiation at a cellular telephone frequency (847.74 MHz, CDMA).
Journal
Radiat Res 156:430-433.
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Authors
Vijayalaxmi, Pickard WF, Bisht KS, Prihoda TJ, et al. (2001)
Title
Micronuclei in the peripheral blood and bone marrow cells of rats exposed to 2450 MHz radiofrequency radiation.
Journal
International Journal of Radiation Biology 77:1109-1115.
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Authors
Vijayalaxmi, Sasser L, Morris JE, Wilson BW, et al.
Title
Genotoxic potential of 1.6 GHz wireless communication signal: in vivo two-year bioassay.
Journal
Radiat Res 2003;159: 558-564.
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Author
Vijayalaxmi.
Title
Cytogenetics studies in human blood lymphocytes exposed in vitro to 2.45 GHz or 8.2 GHz radiofrequency radiation.
Journal
Radiat Res 2006;166:532-538.
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Authors
Whitehead T, Brownstein BH, Parry JJ, Thompson D, et al.
Title
Expression of the proto-oncogene Fos after exposure to radiofrequency radiation relevant to wireless communications.
Journal
Radiat Res 2005;164:420-430.
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Authors
Whitehead TD, Moros EG, Brownstein BH, Roti Roti JL.
Title
Gene expression does not change significantly in C3H 10 T1/2 cells after exposure to 847.74 CDMA or 835.62 FDMA radiofrequency radiation.
Journal
Radiation Research 2006;165:626-635.
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Authors
Whitehead T, Moros EG, Brownstein BH, Roti Roti JL.
Title
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.
Journal
Proteomics 2006b;6:4739-44.
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Authors
Yadav AS, Sharma MK.
Title
Increased frequency of micronucleated exfoliated cells among humans exposed in vivo to mobile telephone radiations.
Journal
Mutation Research/Genetic Toxicology and Environmental Mutagenesis 2008;650(2):175-180.

Authors
Yao K, Wu W, Wang K, Ni S, Ye P, Yu Y, Ye J, Sun L.
Title
Electromagnetic noise inhibits radiofrequency radiation-induced DNA damage and reactive oxygen species increase in human lens epithelial cells.
Journal
Mol Vis 2008;14:964-9.

Authors
Zeng Q, Chen G, Weng Y, Wang L, et al.
Title
Effects of global system for mobile communications 1800 MHz radiofrequency electromagnetic fields on gene and protein expression in MCF-7 cells.
Journal
Proteomics 2006;6:4732-8.
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Authors
Zeni O, Chiavoni AS, Sannino A, Antolini A, et al.
Title
Lack of genotoxic effects (micronucleus induction) in human lymphocytes exposed in vitro to 900 MHz electromagnetic fields.
Journal
Radiat Res 2003;160:152-158.
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Authors
Zeni O, Romano M, Perotta A, Lioi MB, et al.
Title
Evaluation of genotoxic effects in human peripheral blood leukocytes following an acute in vitro exposure to 900 MHz radiofrequency fields.
Journal
Bioelectromagnetics 2005;26:258-265.
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Authors
Zeni O, Schiavoni A, Perrotta A, Forigo D, Deplano M, Scarfi MR.
Title
Evaluation of genotoxic effects in human leukocytes after in vitro exposure to 1950 MHz UMTS radiofrequency field.
Journal
Bioelectromagnetics 2008;29(3);177-184.

Authors
Zhang M-B, Ji-Liang H, Li-Fen J, De-Qiang L (2002):
Title
Study of low-intensity 2450 MHz microwave exposure enhancing the genotoxic effects of Mitomycin C using micronucleus test and comet assay in vitro.
Journal
Biomed Envir Sci 15:283-290.
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Tumour growth and development: Studies in animals of the effects of RF exposure on tumour development or growth fall into one of three categories - changes in spontaneous rates of tumour occurrence; enhancement of the effects of known carcinogens; and alterations in growth of implanted tumours. (Repacholi, 1998; Sienkiewicz, 1997).

Spontaneous tumour development: Several studies have shown an increased incidence of tumours as a result of exposure to RF radiation (Smzigielski 1982, Chou 1992, Repacholi 1997). In contrast, other studies using SARs at moderate levels have shown no increase in tumour rates (Toler 1997, Frei 1998 a,b, Adey 1999, Adey 2000, Zook 2001, Utteridge, 2002, La Regina, 2003, Anderson, 2004, Sommer, 2005, 2007, Tillmann, 2007, Smith, 2007). Utteridge (2002) and Oberto (2007) failed to replicate the findings of Repacholi (1997), who reported a two-fold increase in non-lymphoblastic lymphoma in Pim1 mice exposed for two 30 minute periods per day for 18 months to 217-pulsed 900 MHz RF fields.
).

Enhancement of effects of known carcinogens: In these studies the animals are given a substance that is known to lead to tumour development, and are also exposed to RF radiation. Szmigielski (1982) demonstrated an increased tumour rate in mice whose skin had been painted with benzopyrene. As noted above, the SARs in this study were very high. Other studies have been negative. These have included use of carcinogens such as ethylnitrosurea, which induces brain tumours (Zook, 2001, 2006; Shirai 2005, 2007), diethylnitrosamine, which produces liver cancer (Imaida 1989, 1998); dimethylhydrazine, which induces colon cancer (Wu, 1994); and benzo(a)pyrene, which produces sarcomas (Chagnaud,1999); dimethylbenz(a)anthracene (DMBA), which was used in studies of breast tumours (Bartsch, 2002, Anane, 2003, Yu, 2006) and of skin cancer (Imaida, 2001, Huang, 2005); 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), which is a multi-site carcinogen (Verschaeve 2006, Heikkinen 2006); ultraviolet light (Heikkinen, 2003); and x-rays, which can produce a variety of cancers (Heikkinen, 2001).

Alterations of growth of implanted tumours: A number of studies have used rodents that were implanted with tumour cells and exposed to RF radiation. Tumour types included lymphoreticular sarcoma (Preskorn, 1978), melanoma (Santini, 1988) and brain tumour (Salford 1993, Higashikubo 1999). None of these studies showed any effect on tumour progression.

Most of the evidence from these animal studies suggests that RF radiation exposure does not promote or enhance tumour development. Those studies that have shown an effect on tumour growth have had unusual features. Some have been associated with high SARs and possible thermal effects (e.g. Smzigielski, Repacholi). Chou's study had an unusually low tumour incidence in control animals and no decrease in longevity. Repacholi's study has been replicated (Utteridge 2002) and no increased tumour incidence found. The others have
not yet been replicated (ICNIRP, 1996, Repacholi, 1998, Moulder, 1999, Royal Society of Canada, 1999, UK Independent Expert Group, 2000). French and colleagues (2001) have hypothesized that RF radiation from chronic exposure to mobile phones could induce or promote cancer by causing a heat shock response and the chronic expression of heat shock proteins.

Authors
Adey WR, Byus CB, Cain CD, Higgins RJ, et al.
Title
Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves.
Journal
Radiat Res 1999;152:293-302.
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Authors
Anane R, Dulou P-E, Taxile M, Geffard M, et al.
Title
Effects of GSM-900 microwaves on DMBA-induced mammary gland tumours in female
Sprague-Dawley rats.
Journal
Radiation Research 2003;160:492-497.
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Authors
Anderson LE, Sheen DM, Wilson BW, Grumbein SL, et al.
Title
Two-year chronic bioassay study of rats exposed to a 1.6 GHz radiofrequency signal.
Journal
Radiation Research 2004;162:201-210.
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Authors
Adey WR, Byus CV, Cain CD, Higgins RJ, et al.
Title
Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats exposed to frequency-modulated microwave fields.
Journal
Cancer Research 2000;60:1857-1863.
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Authors
Bartsch H, Bartsch C, Seebald E, Deerberg F, et al.
Title
Chronic exposure to a GSM-like signal (mobile phone) does not stimulate the development of DMBA-induced mammary tumours in rats: Results of three consecutive studies.
Journal
Radiat Res 2002;157:183-190.
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Authors
Chagnaud J-L, Moreau J-M, Veyret B.
Title
No effect of short-term exposure to GSM-modulated low-power microwaves on benzo(a)pyrene-induced tumours in rat.
Journal
Int J Radiat Biol 1999;75:1251-1256.
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Authors
Chou C-K, Guy AW, Kunz LL, Johnson RB, et al.
Title
Long-term, low-level microwave irradiation of rats.
Journal
Bioelectromagnetics 1992;13:469-496.
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Authors
Frei MR, Berger RE, Dusch SJ, Guel V, et al.
Title
Chronic exposure of cancer-prone mice to low-level 2450 MHz radiofrequency radiation.
Journal
Bioelectromagnetics 1998;19:20-31.
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Authors
Frei MR, Jauchem JR, Dusch SJ, Merritt JH, et al.
Title
Chronic, low-level (1.0W/kg) exposure of mice prone to mammary cancer to 2450 MHz microwaves.
Journal
Radiat Res 1998;150:568-576.
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Authors
Heikkinen P, Kosma V-M, Hongisto T, Huuskonen H, et al.
Title
Effects of mobile phone radiation on X-ray induced tumorigenesis in mice
Journal
Radiat Res 2001;156:775-785.
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Authors
Heikkinen P, Kosma V-M, Alhonen L, Huuskonen H, et al. (2003):
Title
Effects of mobile phone radiation on UV-induced skin tumourigenesis in ornithine decarboxylase transgenic and non-transgenic mice.
Journal
Int J Radiat Biol 79:221-233.
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Authors
Heikkinen P, Huuskonen H, Komulainen H, Kumlin T, et al.
Title
No effects of radiofrequency radiation on 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone-induced tumorigenesis in female Wistar rats.
Journal
Radiat Res 2006;166:397-408.
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Authors
Higashikubo R, Culbreth VO, Spitz DR, et al.
Title
Radiofrequency electromagnetic fields have no effect on the in vivo proliferation of the 9L brain tumour.
Journal
Radiat Res 1999;152:665-671.
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Authors
Hoyto A, Sokura M, Juutilainen J, Naarala J.
Title
Radiofrequency radiation does not significantly affect ornithine decarboxylase activity, proliferation, or caspase-3 activity of fibroblasts in different physiological conditions.
Journal
International Journal of Radiation Biology 2008;84( 9):727 – 733.

Authors
Huang T-Q, Lee J-S, Kim T-H, Pack J-K, et al.
Title
Effect of radiofrequency radiation exposure on mouse skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene.
Journal
Int J Radiat Biol 2005;81:861-867.
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Authors
Imaida K, Taki M et al.
Title
Lack of promoting effects of the electromagnetic near-field used for cellular phones (929.2 MHz) on rat liver carcinogenesis in a medium-term liver bioassay.
Journal
Carcinogenesis 1998a;19:311-314.
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Authors
Imaida K, Taki M, et al.
Title
The 1.5 GHz electromagnetic near-field used for cellular phones does not promote rat liver carcinogenesis in a medium-term liver bioassay.
Journal
Jpn J Cancer Res 1998b;89:995-1002.
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Authors
Imaida K, Kuzutani K, Wang J, Fujiwara O, et al.
Title
Lack of promotion of 7,12-dimethylbenz(a)anthracene initiated mouse skin carcinogenesis by 1.5 GHz electromagnetic near fields.
Journal
Carcinogenesis 2001;11:1837-1841.
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Authors
Kim JY, Hong SY, Lee YM, Yu SA, Koh WS, Hong JR, Son T, Chang SK, Lee M.
Title
In vitro assessment of clastogenicity of mobile radiation (835 MHz) using the alkaline comet assay and chromosomal aberration test.
Journal
Environ Toxicol 2008 Jan 23 Epub ahead of print.

Authors
La Regina M, Moros EG, Pickard WF, Straube WL, et al.
Title
The effect of chronic exposure to 835.62 MHz FDMA or 847.74 MHz CDMA
radiofrequency radiation on the incidence of spontaneous tumours in rats.
Journal
Radiat Res 2003;160:143-151.
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Author
Lerchl A.
Title
Comments on "Radiofrequency electromagnetic fields (UMTS, 1,950 MHz) induce genotoxic effects in vitro in human fibroblasts but not in lymphocytes" by Schwarz et al.
Journal
Int Arch Occup Environ Health 2008 Apr 24 Ahead of print.

Authors
Manti, L., Braselmann, H., Calabrese, M. L., Massa, R., Pugliese, M., Scampoli, P., Sicignano, G. and Grossi, G.
Title
Effects of Modulated Microwave Radiation at Cellular Telephone Frequency (1.95 GHz) on X-Ray-Induced Chromosome Aberrations in Human Lymphocytes In Vitro.
Journal
Radiat Res 2008;169(5):575-583.

Authors
Oberto G, Rolfo K, Yu P, Carbonatto M, et al.
Title
Carcinogenicity study of 217 Hz pulsed 900 MHz electromagnetic fields in Pim1 transgenic mice.
Journal
Radiat Res 2007;168:316-326.
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Authors
Preskorn SH, Edwards WD, Justesen DR
Title
Retarded tumor growth and greater longevity in mice after fetal irradiation by 2450-MHz microwaves.
Journal
J Surg Oncol 1978;10:483-492.
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Authors
Repacholi MH, Basten A, et al.
Title
Lymphomas in El-Pim1 transgenic mice exposed to pulsed 900 MHz electromagnetic fields.
Journal
Radiat Res 1997;147:631-640.
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Author
Rüdiger HW.
Title
Answer to comments by A. Lerchl on "Radiofrequency electromagnetic fields (UMTS, 1,950 MHz) induce genotoxic effects in vitro in human fibroblasts but not in lymphocytes" published by C. Schwarz et al. 2008.
Journal
Int Arch Occup Environ Health. 15 May 2008 Ahead of print.

Authors
Salford LG, Brun A, Persson BR, Eberhardt JL
Title
Experimental studies of brain tumour development during exposure to continuous and pulsed 915 MHz radiofrequency radiation.
Journal
Bioelectrochem Bioenerg 1993;30:313-8.
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Authors
Santini R, Hosni M, Deschaux P, Pacheco H
Title
B16 melanoma development in black mice exposed to low-level microwave radiation.
Journal
Bioelectromagnetics 1988;9:105-107.
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Authors
Schwarz C, Kratochvil E, Pilger A, Kuster N, Adlkofer F, Rüdiger HW.
Title
Radiofrequency electromagnetic fields (UMTS, 1,950 MHz) induce genotoxic effects in vitro in human fibroblasts but not in lymphocytes.
Journal
Int Arch Occup Environ Health. 2008;81(6):755-67.

Authors
Shirai T, Kawabe M, Ichihara T, Fujiwara O, et al.
Title
Chronic exposure to 1.439 GHz electromagnetic field used for cellular phones does not promote N-ethylnitrosourea induced central nervous system tumors in F344 rats.
Journal
Bioelectromagnetics 2005;26:59-68.
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Authors
Shirai T, Ichihara T, Wake K, Watanabe S, et al.
Title
Lack of promoting effects of chronic exposure to 1.95 GHz W-CDMA signals for IMT-2000 cellular system on development of N-ethylnitrosurea-induced central nervous system tumors in F334 rats.
Journal
Bioelectromagnetics 2007;28:562-572.
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Authors
Smith P, Kuster N, Ebert S, Chevalier HJ
Title
GSM and DCS wireless communication signals: Combined chronic toxicity/carcinogenicity study in the Wistar rat.
Journal
Radiat Res 2007;168:480-492.
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Authors
Sommer AM, Streckert J, Bitz AK, Hansen VW, et al.
Title
No effects of GSM-modulated 900 MHz electromagnetic fields on survival rate and spontaneous development of lymphoma in female AKR/J mice.
Journal
BMC Cancer 2004;4:77. Published online November 11, 2004.
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Authors
Sommer AM, Bitz AK, Streckert J, Hansen VW, et al.
Title
Lymphoma development in mice chronically exposed to UTMS-modulated radiofrequency electromagnetic fields.
Journal
Radiat Res 2007;168:72-80.
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Authors
Syldona M.
Title
Reducing the in-vitro electromagnetic field effect of cellular phones on human DNA and the intensity of their emitted radiation.
Journal
Acupunct Electrother Res 2007;32(1-2):1-14.

Authors
Szmigielski S, Szudzinski A, Pietraszek A, Bielec M, et al.
Title
Accelerated development of spontaneous and benzopyrene-induced skin cancer in mice exposed to 2450 MHz microwave irradiation.
Journal
Bioelectromagnetics 1982;3:179-191.
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Authors
Tillmann T, Ernst H, Ebert S, Kuster N, et al.
Title
Carcinogenicity study of GSM and DCS wireless communication signals in B6C3F1 mice.
Journal
Bioelectromagnetics 2007;28:173-187.
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Authors
Toler JC, Shelton WW, Frei MR, Merritt JH, et al.
Title
Long-term, low-level exposure of mice prone to mammary tumors to 435 MHz radiofrequency radiation.
Journal
Radiat Res 1997;148:227-234.
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Authors
Utteridge TD, Gebski V, Finnie JW, Vernon-Roberts B, Kuchel TR.
Title
Long-term exposure of Eµ-Pim1 transgenic mice to 898.4 MHz microwaves does not increase lymphoma incidence.
Journal
Radiation Research 2002;158:357-364.
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Authors
Verschaeve L, Heikkinen P, Verheyen G, van Gorp U, et al.
Title
Investigation of co-genotoxic effects of radiofrequency electromagnetic fields in vivo.
Journal
Radiat Res 2006;165:598-607.
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Authors
VIjayalaxmi, Prihoda TJ.
Title
Genetic damage in mammalian somatic cells exposed to radiofrequency radiation: a meta-analysis of data from 63 publications (1990-2005).
Journal
Radiat Res. 2008;169(5):561-74.

Authors
Wu RY, Chiang H, Shao BJ, Li NG, et al.
Title
Effects of 2.45-GHz microwave radiation and phorbol ester 12-O-tetradecanoylphorbol-13-acetate on dimethylhydrazine-induced colon cancer in mice.
Journal
Bioelectromagnetics 1994;15:531-536.
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Authors
Yu D, Shen Y, Kuster N, Fu Y, et al.
Title
Effects of 900 MHz GSM woreless communication signals on DMBA-induced mammary tumors in rats.
Journal
Radiat Res 2006;165:174-180.
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Authors
Zook BC, Simmens SJ.
Title
The effects of 860 MHz radiofrequency radiation on the induction or promotion of brain tumours and other neoplasms in rats.
Journal
Radiat Res 2001;155:572-583.
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Authors
Zotti-Martelli L, Peccatori M, Maggini V, Ballardin M, et al. (2005):
Title
Individual responsiveness to induction of micronuclei in human lymphocytes after exposure in vitro to 1800 MHz microwave radiation.
Journal
Mutat Res 582:42-52.
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