Medical/biological study (experimental study)

Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies med./bio.

By: Friedman J, Kraus S, Hauptman Y, Schiff Y, Seger R

Published in: Biochem J 2007; 405 (3): 559-568

Aim of study (acc. to editor)

To study the effect of electromagnetic fields at mobile phone frequency on the MAPK (mitogen-activated protein kinase) cascades.

Background/further details

MAPK cascades (ERK1/2, JNK1-3, p38MAPK, BMK1) are a group of signal transduction pathways, which mediate the effects of various extracellular stimuli to regulate processes including proliferation, differentiation, metabolism and stress response.
Cells as well as isolated membranes of HeLa cells were used. Different inhibitors (reactive oxygen species inhibitor/scavenger, EGF receptor inhibitor, NADH oxidase inhibitor etc.) were used to identify mediators of irradiation-induced ERKs phosphorylation (signals are transmitted via phosphorylations of protein kinases and of regulatory proteins, for example).

Endpoint

cell function: signal transduction pathways

Exposure

- microwaves
- mobile communications
- digital mobile phone

Exposure	Parameters
Exposure 1: 875 MHz Exposure duration: continuous for 5, 10, (15,) 20, and 30 min	power density: 0.07 mW/cm² power density: 0.23 mW/cm²
Exposure 2: 875 MHz Exposure duration: continuous for 10 min	power density: 0.1 mW/cm² power density: 0.2 mW/cm² power density: 0.31 mW/cm²
Exposure 3: 875 MHz Exposure duration: continuous for 5, 10, 20, and 30 min	power density: 0.005 mW/cm² power density: 0.03 mW/cm² power density: 0.11 mW/cm² power density: 0.31 mW/cm²
Exposure 4: 800–950 MHz Exposure duration: continuous for 5, 10, 20, and 30 min	power density: 0.07 mW/cm²
Exposure 5: 875 MHz Exposure duration: continuous for 10 min	power density: 0.21 mW/cm²
Exposure 6: 875 MHz Exposure duration: continuous for 2 or 12 min	power density: 0.17 mW/cm²
Exposure 7: 875 MHz Exposure duration: continuous for 10 min	power density: 0.04 mW/cm² power density: 0.09 mW/cm² power density: 0.17 mW/cm² power density: 0.27 mW/cm²
Exposure 8: 875 MHz Exposure duration: continuous for 2, 5, 12, and 20 min	power density: 0.31 mW/cm²
Exposure 9: 875 MHz Exposure duration: continuous for 10 or 5 min	power density: 0.2 mW/cm² power density: 0.21 mW/cm² (5 min) power density: 0.22 mW/cm² power density: 0.23 mW/cm² power density: 0.24 mW/cm² power density: 0.25 mW/cm²
Exposure 10: 875 MHz Exposure duration: continuous for 5, 10, and 15 min	power density: 0.344 mW/cm²
Exposure 11: 875 MHz Exposure duration: continuous for 15 and 30 min	power density: 0.3 mW/cm²
Exposure 12: 875 MHz Exposure duration: continuous for 5 and 10 min	power density: 0.24 mW/cm²
Exposure 13: 875 MHz Exposure duration: continuous for 10, 20, and 30 min	power density: 0.2 mW/cm²

Exposure 1

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 5, 10, (15,) 20, and 30 min

Exposure setup

Exposure source	panel antenna at the centre of a shelf in the incubator
Distance between exposed object and exposure source	10 cm
Chamber	The walls of the incubator with 5% CO₂ humidified air at 37°C were covered with RF-absorbing material.
Setup	Cells were irradiated in 6-cm dishes inside the incubator.
Sham exposure	A sham exposure was conducted.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.07 mW/cm²	-	measured	-	-
power density	0.23 mW/cm²	-	measured	-	-

Measurement and calculation details

The density of irradiation was measured using a field meter.

Exposure 2

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 10 min

Exposure setup

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

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.1 mW/cm²	-	measured	-	-
power density	0.2 mW/cm²	-	measured	-	-
power density	0.31 mW/cm²	-	measured	-	-

Exposure 3

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 5, 10, 20, and 30 min

Exposure setup

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

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.005 mW/cm²	-	measured	-	-
power density	0.03 mW/cm²	-	measured	-	-
power density	0.11 mW/cm²	-	measured	-	-
power density	0.31 mW/cm²	-	measured	-	-

Exposure 4

Main characteristics

Frequency	800–950 MHz
Type	electromagnetic field
Exposure duration	continuous for 5, 10, 20, and 30 min
Additional info	800, 875, and 950 MHz were used.

Exposure setup

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

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.07 mW/cm²	-	measured	-	-

Exposure 5

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 10 min

Exposure setup

Exposure source	same setup as exposure 1
Sham exposure	A sham exposure was conducted.
Additional info	After incubation for 20 min with various inhibitors, the cells or controls were either irradiated or left untreated.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.21 mW/cm²	-	measured	-	-

Exposure 6

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 2 or 12 min

Exposure setup

Exposure source	same setup as exposure 1
Sham exposure	A sham exposure was conducted.
Additional info	Some cells were left in the incubator for another 5 or 10 min after their 2-min exposure.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.17 mW/cm²	-	measured	-	-

Exposure 7

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 10 min

Exposure setup

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

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.04 mW/cm²	-	measured	-	-
power density	0.09 mW/cm²	-	measured	-	-
power density	0.17 mW/cm²	-	measured	-	-
power density	0.27 mW/cm²	-	measured	-	-

Exposure 8

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 2, 5, 12, and 20 min

Exposure setup

Exposure source	same setup as exposure 1
Sham exposure	A sham exposure was conducted.
Additional info	Some cells were left in the incubator for another 5 or 10 min after their 2-min exposure.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.31 mW/cm²	-	measured	-	-

Exposure 9

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 10 or 5 min

Exposure setup

Exposure source	same setup as exposure 1
Sham exposure	A sham exposure was conducted.
Additional info	After incubation for 20 min with various inhibitors, the cells or controls were irradiated with intensities depending on the inhibitors or left untreated.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.2 mW/cm²	-	measured	-	-
power density	0.21 mW/cm²	-	measured	-	5 min
power density	0.22 mW/cm²	-	measured	-	-
power density	0.23 mW/cm²	-	measured	-	-
power density	0.24 mW/cm²	-	measured	-	-
power density	0.25 mW/cm²	-	measured	-	-

Exposure 10

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 5, 10, and 15 min

Exposure setup

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

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.344 mW/cm²	-	measured	-	-

Exposure 11

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 15 and 30 min

Exposure setup

Exposure source	same setup as exposure 1
Setup	Membranes suspended in PBS (100 µl) were irradiated in a thin tube inside the incubator.
Sham exposure	A sham exposure was conducted.
Additional info	After incubation for 15 min with various inhibitors, the membranes or controls were either irradiated or left untreated.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.3 mW/cm²	-	measured	-	-

Exposure 12

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 5 and 10 min

Exposure setup

Exposure source	same setup as exposure 1
Setup	Membranes suspended in PBS (100 µl) were irradiated in a thin tube inside the incubator.
Sham exposure	A sham exposure was conducted.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.24 mW/cm²	-	measured	-	-

Exposure 13

Main characteristics

Frequency	875 MHz
Type	electromagnetic field
Exposure duration	continuous for 10, 20, and 30 min

Exposure setup

Exposure source	same setup as exposure 1
Sham exposure	A sham exposure was conducted.
Additional info	After incubation for 15 or 30 min with DPI, the membranes or cells and controls were either irradiated or left untreated.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
power density	0.2 mW/cm²	-	measured	-	-

Exposed system:

Methods Endpoint/measurement parameters/methodology

molecular biosynthesis: detection and kinetics of phosphorylation of ERKs, JNKs, p38MAPKs (Western blot; densitometry); release of heparin-binding-epidermal growth factor (hb-EGF) and ERK actication by hb-EGF (Western blot)
cell function: signal transduction pathways (detection of different molecules (see "molecular biosynthesis") and enzyme activity of NADH oxidase (spectrophotometry))

Investigated system:

isolated bio./chem. substance
organelle/cell part
cell homogenates/supernatants; membrane suspensions

Time of investigation:

after exposure

Main outcome of study (acc. to author)

This study delineate a detailed molecular mechanism by which electromagnetic fields at mobile phone frequency induces short-term MAPK activation and thereby transcription and other cellular processes.
The data show that ERKs, but not JNKs or p38MAPKs, are rapidly activated in response to mobile phone exposure at various frequencies and intensities. The first step is mediated in the plasma membrane by NADH oxidase, which rapidly generates reactive oxygen species. The generated reactive oxygen species then directly activate matrix metalloproteinases to release heparin-binding (Hb)-EGF, which further activate the ERK cascade.

Study character:

medical/biological study
experimental study
full/main study

Study funded by

La Fondation Raphael et Regina Levy, France

Comments on this article

No authors listed (2020): Expression of Concern: Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies
Arthur JS (2007): MAPK activation by radio waves
Williams C (2007): Can 'cold calls' affect your brain?

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Sun W et al. (2012): A 1.8-GHz radiofrequency radiation induces EGF receptor clustering and phosphorylation in cultured human amniotic (FL) cells
Yu Y et al. (2008): Effects of exposure to 1.8 GHz radiofrequency field on the expression of Hsps and phosphorylation of MAPKs in human lens epithelial cells
Lee KS et al. (2008): Mobile phone electromagnetic radiation activates MAPK signaling and regulates viability in Drosophila
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Vanderwaal RP et al. (2006): HSP27 phosphorylation increases after 45°C or 41°C heat shocks but not after non-thermal TDMA or GSM exposures
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Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies med./bio.

Aim of study (acc. to editor)

Background/further details

Endpoint

Exposure

Exposure 1

Main characteristics

Exposure setup

Parameters

Measurement and calculation details

Exposure 2

Main characteristics

Exposure setup

Parameters

Exposure 3

Main characteristics

Exposure setup

Parameters

Exposure 4

Main characteristics

Exposure setup

Parameters

Exposure 5

Main characteristics

Exposure setup

Parameters

Exposure 6

Main characteristics

Exposure setup

Parameters

Exposure 7

Main characteristics

Exposure setup

Parameters

Exposure 8

Main characteristics

Exposure setup

Parameters

Exposure 9

Main characteristics

Exposure setup

Parameters

Exposure 10

Main characteristics

Exposure setup

Parameters

Exposure 11

Main characteristics

Exposure setup

Parameters

Exposure 12

Main characteristics

Exposure setup

Parameters

Exposure 13

Main characteristics

Exposure setup

Parameters

Methods Endpoint/measurement parameters/methodology

Main outcome of study (acc. to author)

Study funded by

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