Medical/biological study (experimental study)

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 radio base stations med./bio.

By: Hirose H, Sakuma N, Kaji N, Suhara T, Sekijima M, Nojima T, Miyakoshi J

Published in: Bioelectromagnetics 2006; 27 (6): 494-504

Aim of study (acc. to author)

To test the hypothesis that modulated radiofrequency fields from mobile radio base stations induce apoptosis or other cellular stress response that activate p53 or the p53-signaling pathway (and thus important regulators of apoptosis).

Background/further details

Phosphorylation of p53 is believed to be one of the mechanisms by which p53 is activated or stabilized in response to cell stress.
Cells treated with doxorubicin were used as positive controls for the induction of apoptosis and cells treated with doxorubicin or heat shock were used as positive controls for p53 phosphorylation and gene expression.

Endpoint

cell viability/cell division/proliferation: apoptosis
cellular stress response

Exposure

- CDMA
- mobile communications
- mobile phone base station

Exposure	Parameters
Exposure 1: 2.1425 GHz Exposure duration: continuous for 24 or 48 h A172 cells	SAR: 80 mW/kg mean (correspondends to the ICNIRP limit for the average whole-body SAR value) SAR: 250 mW/kg mean (correspondends to three times the ICNIRP limit for the average whole-body SAR value) SAR: 800 mW/kg mean (correspondends to ten times the ICNIRP limit for the average whole-body SAR value)
Exposure 2: 2.1425 GHz Exposure duration: continuous for 28 h IMR-90 cells	SAR: 80 mW/kg mean (±47%)
Exposure 3: 2.1425 GHz Modulation type: CW Exposure duration: continuous for 24 or 48 h (A172) or 28 h (IMR-90)	SAR: 80 mW/kg mean (±47%)

Exposure 1

Main characteristics

Frequency	2.1425 GHz
Type	electromagnetic field
Exposure duration	continuous for 24 or 48 h
Additional info	A172 cells

Modulation

Modulation type	cf. additional info
Additional info	The W-CDMA component of the IMT-2000 cellular system adopts Direct Sequence CDMA (DS-CDMA) and Frequency Division Duplex (FDD) as a multiple access and duplex scheme. The chip rate of the spread code is 3.84 megachip per second (Mcps).

Exposure setup

Exposure source	horn antenna anechoic chamber base transceiver station dielectric lens
Setup	The system allowed simultaneous exposure of 49 (7 x 7 array) 35-mm culture dishes with a similar SAR uniformity within each dish [Iyama et al., 2004]. Twelve dishes in the inner 25 culture dishes were used in this study.
Sham exposure	A sham exposure was conducted.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
SAR	80 mW/kg	mean	-	-	correspondends to the ICNIRP limit for the average whole-body SAR value
SAR	250 mW/kg	mean	-	-	correspondends to three times the ICNIRP limit for the average whole-body SAR value
SAR	800 mW/kg	mean	-	-	correspondends to ten times the ICNIRP limit for the average whole-body SAR value

Additional parameter details

The mean SAR of the culture fluid at the bottom of the inner 25 culture dishes (5 x 5 array) was 139 mW/kg for an antenna input power of 1 W, and the standard deviation of the SAR distribution was 47%.

Exposure 2

Main characteristics

Frequency	2.1425 GHz
Type	electromagnetic field
Exposure duration	continuous for 28 h
Additional info	IMR-90 cells

Modulation

Modulation type	cf. additional info
Additional info	The W-CDMA component of the IMT-2000 cellular system adopts Direct Sequence CDMA (DS-CDMA) and Frequency Division Duplex (FDD) as a multiple access and duplex scheme. The chip rate of the spread code is 3.84 megachip per second (Mcps).

Exposure setup

Exposure source	same setup as exposure 1
Sham exposure	A sham exposure was conducted.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
SAR	80 mW/kg	mean	-	-	±47%

Exposure 3

Main characteristics

Frequency	2.1425 GHz
Type	electromagnetic field
Exposure duration	continuous for 24 or 48 h (A172) or 28 h (IMR-90)

Modulation

Modulation type	CW

Exposure setup

Exposure source	same setup as exposure 1
Sham exposure	A sham exposure was conducted.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
SAR	80 mW/kg	mean	-	-	±47%

Reference articles

Iyama T et al. (2004): Large scale in vitro experiment system for 2 GHz exposure

Exposed system:

intact cell/cell culture
A172 (human glioblastoma cells) and IMR90 fibroblasts (from fetal lungs)

Methods Endpoint/measurement parameters/methodology

molecular biosynthesis: phosphorylation of p53 (at serine 15) and gene expression of p53 (bead-based multiplex assay (immunoassay)); p53-related gene expression (RNA microarray (HG-U133 Plus2.0, Affymetrix); RT-PCR)
cell viability/cell division/proliferation: apoptosis (Annexin V-FITC assay; flow cytometry)
cellular stress response (see "molecular biosynthesis")

Investigated system:

Time of investigation:

after exposure

Main outcome of study (acc. to author)

The data showed that p53 phosphorylation in the two cell lines investigated is not induced by exposure to 2.1425 GHz W-CDMA or CW signal. Moreover, changes in expression levels of the p53 protein and p53-related genes, and the frequency of apoptotis were not induced by any of the radiofrequency exposures.

Study character:

medical/biological study
experimental study
full/main study
blind study

Study funded by

NTT DoCoMo, Japan

Esmekaya MA et al. (2017): Mitochondrial hyperpolarization and cytochrome-c release in microwave-exposed MCF-7 cells
Akhavan-Sigari R et al. (2014): Connection between Cell Phone use, p53 Gene Expression in Different Zones of Glioblastoma Multiforme and Survival Prognoses
Esmekaya MA et al. (2013): Investigation of the effects of 2.1 GHz microwave radiation on mitochondrial membrane potential (DeltaPsim), apoptotic activity and cell viability in human breast fibroblast cells
Bourthoumieu S et al. (2013): Study of p53 expression and post-transcriptional modifications after GSM-900 radiofrequency exposure of human amniotic cells
Roux D et al. (2011): Human keratinocytes in culture exhibit no response when exposed to short duration, low amplitude, high frequency (900 MHz) electromagnetic fields in a reverberation chamber
Sekijima M et al. (2010): 2-GHz band CW and W-CDMA modulated radiofrequency fields have no significant effect on cell proliferation and gene expression profile in human cells
Brescia F et al. (2009): Reactive oxygen species formation is not enhanced by exposure to UMTS 1950 MHz radiation and co-exposure to ferrous ions in Jurkat cells
Sanchez S et al. (2008): Effect of GSM-900 and -1800 signals on the skin of hairless rats. III: Expression of heat shock proteins
Chauhan V et al. (2007): Analysis of gene expression in two human-derived cell lines exposed in vitro to a 1.9 GHz pulse-modulated radiofrequency field
Sanchez S et al. (2007): In Vitro Study of the Stress Response of Human Skin Cells to GSM-1800 Mobile Phone Signals Compared to UVB Radiation and Heat Shock
Zhao R et al. (2007): Studying gene expression profile of rat neuron exposed to 1800 MHz radiofrequency electromagnetic fields with cDNA microassay
Hirose H et al. (2007): Mobile phone base station-emitted radiation does not induce phosphorylation of Hsp27
Lee JS et al. (2006): Radiofrequency radiation does not induce stress response in human T-lymphocytes and rat primary astrocytes
Qutob SS et al. (2006): Microarray gene expression profiling of a human glioblastoma cell line exposed in vitro to a 1.9 GHz pulse-modulated radiofrequency field
Takashima Y et al. (2006): Effects of continuous and intermittent exposure to RF fields with a wide range of SARs on cell growth, survival, and cell cycle distribution
Chauhan V et al. (2006): Gene Expression Analysis of a Human Lymphoblastoma Cell Line Exposed In Vitro to an Intermittent 1.9 GHz Pulse-Modulated Radiofrequency Field
Hook GJ et al. (2004): Measurement of DNA damage and apoptosis in Molt-4 cells after in vitro exposure to radiofrequency radiation
Capri M et al. (2004): In vitro exposure of human lymphocytes to 900 MHz CW and GSM modulated radiofrequency: studies of proliferation, apoptosis and mitochondrial membrane potential
Czyz J et al. (2004): High frequency electromagnetic fields (GSM signals) affect gene expression levels in tumor suppressor p53-deficient embryonic stem cells
Leszczynski D et al. (2002): Non-thermal activation of the hsp27/p38MAPK stress pathway by mobile phone radiation in human endothelial cells: Molecular mechanism for cancer- and blood-brain barrier-related effects

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 radio base stations med./bio.

Aim of study (acc. to author)

Background/further details

Endpoint

Exposure

Exposure 1

Main characteristics

Modulation

Exposure setup

Parameters

Additional parameter details

Exposure 2

Main characteristics

Modulation

Exposure setup

Parameters

Exposure 3

Main characteristics

Modulation

Exposure setup

Parameters

Reference articles

Methods Endpoint/measurement parameters/methodology

Main outcome of study (acc. to author)

Study funded by

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