Pre-Exposure to 50 Hz Magnetic Fields Modifies Menadione-Induced Genotoxic Effects in Human SH-SY5Y Neuroblastoma Cells

Abstract

BackgroundExtremely low frequency (ELF) magnetic fields (MF) are generated by power lines and various electric appliances. They have been classified as possibly carcinogenic by the International Agency for Research on Cancer, but a mechanistic explanation for carcinogenic effects is lacking. A previous study in our laboratory showed that pre-exposure to ELF MF altered cancer-relevant cellular responses (cell cycle arrest, apoptosis) to menadione-induced DNA damage, but it did not include endpoints measuring actual genetic damage. In the present study, we examined whether pre-exposure to ELF MF affects chemically induced DNA damage level, DNA repair rate, or micronucleus frequency in human SH-SY5Y neuroblastoma cells.Methodology/Principal FindingsExposure to 50 Hz MF was conducted at 100 µT for 24 hours, followed by chemical exposure for 3 hours. The chemicals used for inducing DNA damage and subsequent micronucleus formation were menadione and methyl methanesulphonate (MMS). Pre-treatment with MF enhanced menadione-induced DNA damage, DNA repair rate, and micronucleus formation in human SH-SY5Y neuroblastoma cells. Although the results with MMS indicated similar effects, the differences were not statistically significant. No effects were observed after MF exposure alone.ConclusionsThe results confirm our previous findings showing that pre-exposure to MFs as low as 100 µT alters cellular responses to menadione, and show that increased genotoxicity results from such interaction. The present findings also indicate that complementary data at several chronological points may be critical for understanding the MF effects on DNA damage, repair, and post-repair integrity of the genome.

Induction of micronuclei and superoxide production in neuroblastoma and glioma cell lines exposed to weak 50 Hz magnetic fields

“…We have previously shown that exposure to ELF MFs (50 Hz, 100-300 mT) alter cellular responses to DNA damage induced by menadione (MQ), resulting in decreased integrity of the genome [13,14]. A more recent study also indicated that similar exposure may induce genomic instability (persistently elevated frequency of genetic changes in the progeny of exposed cells), which is highly relevant for possible carcinogenic effects [15].…”

Influence of a 50 Hz magnetic field and of all-trans‑retinol on the proliferation of human cancer cell lines

“…In order to identify and characterize the cellular processes involved in the potential proliferative effects of ELF MF, a number of studies have investigated the in vitro response to those fields when administered in combination with different chemical species including antioxidants like melatonin or tamoxifen (14)(15)(16)(17)(18)(19), or radical-inducing agents like menadione (20) and tumor promoters like DMBA (21).…”

The effects of extremely low frequency magnetic fields on mutation induction in mice

“…Conversely, the experimental data produced in relation to the potential genotoxicity of ELF-MF exposure are reminiscent of that produced by epidemiological studies in that it is moderately conflicting. This point was typified by the intra-laboratory inconsistencies published by Luukkonen et al (2011) and Luukkonen et al (2014) who in contrast to their earlier study (Luukkonen et al, 2011), more recently illustrated that ELF-MF exposure (100 µT, 24 hours) was able to induce micronuclei in human SH-SY5Y neuroblastoma cells at 8 and 15 days postexposure (Luukkonen et al, 2014).…”

“…Despite this, the majority of studies conducted to date have found no consistent evidence of magnetic field induced effects on genotoxicity using an array of field intensities: 0.001-1 mT (Paile et al, 1995;Luceri et al, 2005;Stronati et al, 2004;Testa et al, 2004;Luukkonen et al, 2011;Saha et al, 2014), and 5-400 mT (Antonopoulos et al, 1995;Tateno et al, 1998;Miyakoshi et al, 2000). Yet there have also been several studies, both in vivo and in vitro where positive correlations have been reported; for example a significant three-fold elevation in SCE was observed in mouse m5S cells exposed to 400 mT (50 Hz) for 40 hours (Yaguchi et al, 1999).…”

“…Moreover, multiple studies signified that cells pre-treated with the tumour initiator benzo(a)pyrene (BP), and then co-exposed with benzene and 0.8-1 mT ELF-MF introduced an increase in the comet tail moment , as well as a significant dose dependent increase in the frequency of sister chromatid exchanges and micronuclei formation (Cho & Chung, 2003). A combination of 3 mT ELF-MF and xenobiotic (N-methyl-N0-nitro-N-nitrosoguanidine (MNNG)) induced DNA damage in human leukocytes (Villarini et al, 2006), while exposure to ELF-MF at field strengths as low as 100 µT for 24 hours have been illustrated to increase the menadione-induced DNA damage and MN formation in human neuroblastoma cells (Luukkonen et al, 2011).…”