Study type: Medical/biological study (experimental study)

Involvement of the EGF Receptor in MAPK Signaling Activation by a 50 Hz Magnetic Field in Human Neuroblastoma Cells. med./bio.

Published in: Cell Physiol Biochem 2019; 52 (4): 893-907

Aim of study (acc. to author)

The effects of exposure of human neuroblastoma cells to a 50 Hz magnetic field on potential involvement of the epidermal growth factor receptor (EGFR) in induction of cell proliferation and activation of MAPK signal pathways should be investigated.

Background/further details

Previous studies by the authors have shown that exposure of human neuroblastoma cells to a 50 Hz magnetic field could induce cell proliferation which was mediated by activation of MAPK pathways (Martinez et al. 2012, Martinez et al. 2016).
The cells were divided into the following groups: exposure to the magnetic field for 1) 5 minutes, 2) 10 minutes, 3) 15 minutes, 4) 20 minutes, 5) 30 minutes and 6) 63 hours intermittently. Cells were examined with or without addition of erlotinib, an inhibitor of EGFR tyrosine kinase. For each exposure group, a respective sham exposure was conducted. Between 3 and 7 replicates of each test were performed, using between 3 and 4 samples per experimental condition and replicate.

Endpoint

Exposure

Exposure Parameters
Exposure 1: 50 Hz
Exposure duration: 5 minutes
Exposure 2: 50 Hz
Exposure duration: 10 minutes
Exposure 3: 50 Hz
Exposure duration: 15 minutes
Exposure 4: 50 Hz
Exposure duration: 20 minutes
Exposure 5: 50 Hz
Exposure duration: 30 minutes
Exposure 6: 50 Hz
Exposure duration: intermittent (3 h on/3 h off) for 63 hours

Exposure 1

Main characteristics
Frequency 50 Hz
Type
Waveform
Polarization
Exposure duration 5 minutes
Exposure setup
Exposure source
Chamber Petri dishes inside magnetically shielded chamber in CO2 incubator
Setup a generator was connected to 2 pairs of coils set in Helmholtz configuration; each pair of coils was placed in an incubator; no increase of temperature at the samples location was measured during exposure; 5 Petri dishes per experimental group were stacked in the central region of the Helmholtz coil gap, in which magnetic field was uniform; following a random sequence, only one of the two identical coil sets was energized in each experimental run, with the samples located in the unenergized set considered sham-exposed controls
Sham exposure A sham exposure was conducted.
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 100 µT effective value measured - -

Exposure 2

Main characteristics
Frequency 50 Hz
Type
Waveform
Polarization
Exposure duration 10 minutes
Exposure setup
Exposure source
Sham exposure A sham exposure was conducted.
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 100 µT effective value measured - -

Exposure 3

Main characteristics
Frequency 50 Hz
Type
Waveform
Polarization
Exposure duration 15 minutes
Exposure setup
Exposure source
Sham exposure A sham exposure was conducted.
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 100 µT effective value measured - -

Exposure 4

Main characteristics
Frequency 50 Hz
Type
Waveform
Polarization
Exposure duration 20 minutes
Exposure setup
Exposure source
Sham exposure A sham exposure was conducted.
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 100 µT effective value measured - -

Exposure 5

Main characteristics
Frequency 50 Hz
Type
Waveform
Polarization
Exposure duration 30 minutes
Exposure setup
Exposure source
Sham exposure A sham exposure was conducted.
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 100 µT effective value measured - -

Exposure 6

Main characteristics
Frequency 50 Hz
Type
Waveform
Polarization
Exposure duration intermittent (3 h on/3 h off) for 63 hours
Exposure setup
Exposure source
Sham exposure A sham exposure was conducted.
Parameters
Measurand Value Type Method Mass Remarks
magnetic flux density 100 µT effective value measured - -

Reference articles

  • Martinez MA et al. (2012): The Proliferative Response of NB69 Human Neuroblastoma Cells to a 50 Hz Magnetic Field is mediated by ERK1/2 Signaling.
  • Trillo MA et al. (2012): Influence of a 50 Hz magnetic field and of all-transretinol on the proliferation of human cancer cell lines.

Exposed system:

Methods Endpoint/measurement parameters/methodology

Investigated system:
Time of investigation:
  • before exposure
  • after exposure

Main outcome of study (acc. to author)

Exposure to the magnetic field for 63 hours (group 6) led to a significant increase in cell proliferation compared to sham exposure, what was blocked by erlotinib. Different short term exposure durations (groups 1-5) induced a significant increase in protein expression of p-EGFR, p-ERK1/2, p-p38 MAPK and p-SAPK/JNK compared to sham exposure, what was also blocked by erlotinib. Moreover, MMP-9 expression was significantly increased after 5 minutes of exposure to the magnetic field (group 1) compared to sham exposure.
The authors concluded that exposure of human neuroblastoma cells to a 50 Hz magnetic field could increase cell proliferation via activation of MAPK signal pathways. This is mediated by an early transient activation of EGFR in which MMP-9 could be involved.

Study character:

Study funded by

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