Medical/biological study (experimental study)

Effects of extremely low frequency electromagnetic field and cisplatin on mRNA levels of some DNA repair genes med./bio.

By: Sanie-Jahromi F, Saadat I, Saadat M

Published in: Life Sci 2016; 166: 41-45

Aim of study (acc. to author)

The effects of co-exposure of two cancer cell lines to different 50 Hz magnetic fields and cisplatin on gene expression of genes involved in DNA repair should be investigated in view of a possible therapeutic use.

Background/further details

Two 50 Hz magnetic flux densities (0.25 and 0.50 mT), three exposure patterns (5 min field "on"/5 min field "off", 15 min field "on"/15 min field "off", continuously 30 min field "on") and two cell lines (MCF-7 and SHSY5Y) were used.
To test whether exposure to the magnetic field might sensitize cells to cisplatin, several groups were also tested in a co-exposure with cisplatin (15 µg/ml for MCF-7 cells, 4 µg/m for SH-SY5Y cells). To test whether co-exposure to the magnetic field and cisplatin might sensitize cells to double-strand breaks from, e.g., irradiation therapy, some co-exposed cells were treated with 1 µg/ml bleomycin, an irradiation mimicking drug.

Endpoint

molecular biosynthesis: gene expression of genes involved in DNA repair

Exposure

Exposure	Parameters
Exposure 1: 50 Hz Exposure duration: intermittent 5 min field "on"/5 min field "off" for 30 minutes MCF-7 cells	magnetic flux density: 0.25 mT
Exposure 2: 50 Hz Exposure duration: intermittent 15 min field "on"/15 min field "off" for 30 minutes MCF-7 cells	magnetic flux density: 0.25 mT
Exposure 3: 50 Hz Exposure duration: continuous for 30 minutes MCF-7 cells	magnetic flux density: 0.25 mT
Exposure 4: 50 Hz Exposure duration: intermittent 5 min field "on"/5 min field "off" for 30 minutes MCF-7 cells	magnetic flux density: 0.5 mT
Exposure 5: 50 Hz Exposure duration: intermittent 15 min field "on"/15 min field "off" for 30 minutes MCF-7 cells, SH-SY5Y cells, partially with cisplatin and bleomycin	magnetic flux density: 0.5 mT
Exposure 6: 50 Hz Exposure duration: continuous for 30 minutes MCF-7 cells	magnetic flux density: 0.5 mT

Exposure 1

Main characteristics

Frequency	50 Hz
Type	magnetic field
Exposure duration	intermittent 5 min field "on"/5 min field "off" for 30 minutes
Additional info	MCF-7 cells

Exposure setup

Exposure source	solenoid
Chamber	10 cm Petri dishes
Setup	culture dishes were placed on the axis of the solenoid to achieve an almost uniform exposure; temperature changes were monitored during exposure time and no change was observed
Sham exposure	A sham exposure was conducted.

Parameters

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	0.25 mT	-	-	-	-

Exposure 2

Main characteristics

Frequency	50 Hz
Type	magnetic field
Exposure duration	intermittent 15 min field "on"/15 min field "off" for 30 minutes
Additional info	MCF-7 cells

Exposure setup

Exposure source	same setup as exposure 1

Parameters

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	0.25 mT	-	-	-	-

Exposure 3

Main characteristics

Frequency	50 Hz
Type	magnetic field
Exposure duration	continuous for 30 minutes
Additional info	MCF-7 cells

Exposure setup

Exposure source	same setup as exposure 1

Parameters

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	0.25 mT	-	-	-	-

Exposure 4

Main characteristics

Frequency	50 Hz
Type	magnetic field
Exposure duration	intermittent 5 min field "on"/5 min field "off" for 30 minutes
Additional info	MCF-7 cells

Exposure setup

Exposure source	same setup as exposure 1

Parameters

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	0.5 mT	-	-	-	-

Exposure 5

Main characteristics

Frequency	50 Hz
Type	magnetic field
Exposure duration	intermittent 15 min field "on"/15 min field "off" for 30 minutes
Additional info	MCF-7 cells, SH-SY5Y cells, partially with cisplatin and bleomycin

Exposure setup

Exposure source	same setup as exposure 1

Parameters

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	0.5 mT	-	-	-	-

Exposure 6

Main characteristics

Frequency	50 Hz
Type	magnetic field
Exposure duration	continuous for 30 minutes
Additional info	MCF-7 cells

Exposure setup

Exposure source	same setup as exposure 1

Parameters

Measurand	Value	Type	Method	Mass	Remarks
magnetic flux density	0.5 mT	-	-	-	-

Reference articles

Mahmoudinasab H et al. (2016): Effects of extremely low-frequency electromagnetic field on expression levels of some antioxidant genes in human MCF-7 cells

Exposed system:

intact cell/cell culture
MCF-7 (human breast cancer cell line) and SH-SY5Y (human neuroblastoma cell line)

Methods Endpoint/measurement parameters/methodology

molecular biosynthesis: gene expression of genes involved in DNA repair (GADD45A, XRCC1, XRCC4, Ku70, Ku80, DNA-PKcs and LIG4, immediately, 2 h and 4 h after exposure; real-time RT-PCR)
cell viability/cell division/proliferation: cell viability (with exposure field 5, 24 h after exposure, percentaged and as IC₅₀ of cisplatin; MTT assay)

Investigated system:

Time of investigation:

after exposure

Main outcome of study (acc. to author)

A general trend towards a down-regulation of DNA repair involved genes was found in exposed cells compared to sham exposed cells. Intermittent exposure of field 5 (15 min field "on"/15 min field "off" with 0.5 mT) showed the most distinct results with significantly downregulated genes (GADD45A, XRCC1, XRCC4, Ku80, Ku70 and LIG4).
A significant elevation of the IC50 was found in cells co-exposed to the magnetic field and cisplatin (field 5) compared to a cisplatin treatment alone, indicating that magnetic field exposure did not sensitize cells to cisplatin.
However, co-exposure to the magnetic field and cisplatin significantly decreased the gene expressions of XRCC4, Ku80, Ku70 and DNA-PKcs (field 5) compared to sham exposed cells, while the gene expression of GADD45A was significantly downregulated. This was not observed in cells exposed to cisplatin alone. Cell viability was significantly reduced in a co-exposure to the magnetic field, cisplatin and bleomycin compared to a treatment with cisplatin and bleomycin alone, indicating that cells co-exposed to the magnetic field and cisplatin were sensitized to bleomycin.
The authors conclude that co-exposure to a 50 Hz magnetic field and cisplatin might downregulate genes involved in DNA repair, what could sensitize cancer cells to double-strand break-inducing drugs and irradiation therapy.

Study character:

medical/biological study
experimental study
full/main study

Study funded by

Shiraz University, Shiraz, Iran

Luukkonen J et al. (2017): Modification of p21 level and cell cycle distribution by 50 Hz magnetic fields in human SH-SY5Y neuroblastoma cells
Falone S et al. (2017): Power frequency magnetic field promotes a more malignant phenotype in neuroblastoma cells via redox-related mechanisms
Baharara J et al. (2016): Extremely low frequency electromagnetic field sensitizes cisplatin-resistant human ovarian adenocarcinoma cells via P53 activation
Mahmoudinasab H et al. (2016): Effects of extremely low-frequency electromagnetic field on expression levels of some antioxidant genes in human MCF-7 cells
Hasanzadeh H et al. (2014): Effect of ELF-EMF Exposure on Human Neuroblastoma Cell Line: a Proteomics Analysis
El-Bialy NS et al. (2013): Extremely Low-Frequency Magnetic Field Enhances the Therapeutic Efficacy of Low-Dose Cisplatin in the Treatment of Ehrlich Carcinoma
Crocetti S et al. (2013): Low intensity and frequency pulsed electromagnetic fields selectively impair breast cancer cell viability
Zimmerman JW et al. (2012): Cancer cell proliferation is inhibited by specific modulation frequencies
Buldak RJ et al. (2012): Short-term exposure to 50 Hz ELF-EMF alters the cisplatin-induced oxidative response in AT478 murine squamous cell carcinoma cells
Kakikawa M et al. (2012): Effect of Extremely Low-Frequency (ELF) Magnetic Fields on Anticancer Drugs Potency
Sulpizio M et al. (2011): Molecular basis underlying the biological effects elicited by extremely low-frequency magnetic field (ELF-MF) on neuroblastoma cells
Ruiz-Gomez MJ et al. (2008): No effect of 50 Hz 2.45 mT magnetic field on the potency of cisplatin, mitomycin C, and methotrexate in S. cerevisiae
Li H et al. (2005): Effects of ELF magnetic fields on protein expression profile of human breast cancer cell MCF7
Ruiz-Gomez MJ et al. (2002): Influence of 1 and 25 Hz, 1.5 mT magnetic fields on antitumor drug potency in a human adenocarcinoma cell line
Pang L et al. (2002): ELF-electromagnetic fields inhibit the proliferation of human cancer cells and induce apoptosis
Loberg LI et al. (2000): Cell viability and growth in a battery of human breast cancer cell lines exposed to 60 Hz magnetic fields

Effects of extremely low frequency electromagnetic field and cisplatin on mRNA levels of some DNA repair genes med./bio.

Aim of study (acc. to author)

Background/further details

Endpoint

Exposure

Exposure 1

Main characteristics

Exposure setup

Parameters

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

Reference articles

Methods Endpoint/measurement parameters/methodology

Main outcome of study (acc. to author)

Study funded by

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