Assessing the combined effect of extremely low-frequency magnetic field exposure and oxidative stress on LINE-1 promoter methylation in human neural cells
- 282 Downloads
Extremely low frequency magnetic fields (ELF-MF) have been classified as “possibly carcinogenic”, but their genotoxic effects are still unclear. Recent findings indicate that epigenetic mechanisms contribute to the genome dysfunction and it is well known that they are affected by environmental factors. To our knowledge, to date the question of whether exposure to ELF-MF can influence epigenetic modifications has been poorly addressed. In this paper, we investigated whether exposure to ELF-MF alone and in combination with oxidative stress (OS) can affect DNA methylation, which is one of the most often studied epigenetic modification. To this end, we analyzed the DNA methylation levels of the 5′untranslated region (5′UTR) of long interspersed nuclear element-1s (LINE-1 or L1), which are commonly used to evaluate the global genome methylation level. Human neural cells (BE(2)C) were exposed for 24 and 48 h to extremely low frequency pulsed magnetic field (PMF; 50 Hz, 1 mT) in combination with OS. The methylation levels of CpGs located in L1 5′UTR region were measured by MassARRAY EpiTYPER. The results indicate that exposures to the single agents PMF and OS induced weak decreases and increases of DNA methylation levels at different CpGs. However, the combined exposure to PMF and OS lead to significant decrease of DNA methylation levels at different CpG sites. Most of the changes were transient, suggesting that cells can restore homeostatic DNA methylation patterns. The results are discussed and future research directions outlined.
KeywordsDNA methylation Epigenetics LINE-1 Retrotransposition Extremely low frequency magnetic field Oxidative stress
This work was supported by RFO (Ricerca Fondamentale Orientata, Oriented Fundamental Research) grants from the University of Bologna to BDR and to MC. Funds were also obtained by Fondazione Pallotti to PG and MC.
Compliance with ethical standards
Conflict of interest
The authors report no conflicts of interests. The authors alone are responsible for the content and writing of the paper.
- Biedler JL, Roffler-Tarlov S, Schachner M, Freedman LS (1978) Multiple neurotransmitter synthesis by human neuroblastoma cell lines and clones. Cancer Res 38:3751–3757Google Scholar
- Denli AM, Narvaiza I, Kerman B, Pena M, Benner C, Marchetto MC, Diedrich JK, Aslanian A, Ma J, Moresco JJ, Moore L, Hunter T, Saghatelian A, Gage FH (2015) Primate-specific ORF0 contributes to retrotransposon-mediated diversity. Cell 163:583–593. doi: 10.1016/j.cell.2015.09.025 CrossRefGoogle Scholar
- Giorgi G, Lecciso M, Capri M, Lukas Yani S, Virelli A, Bersani F, Del Re B (2014) An evaluation of genotoxicity in human neuronal-type cells subjected to oxidative stress under an extremely low frequency pulsed magnetic field. Mutat Res Genet Toxicol Environ Mutagen 775–776:31–37CrossRefGoogle Scholar
- IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2002) Non-ionizing radiation, Part 1: static and extremely low-frequency (ELF) electric and magnetic fields. IARC Monogr Eval Carcinog Risks Hum 80:1–395Google Scholar
- Li Z, Doho G, Zheng X, Jella KK, Li S, Wang Y, Dynan WS (2015) Co-culturing with high-charge and energy particle irradiated cells Increases mutagenic joining of enzymatically induced DNA double-strand breaks in nonirradiated Cells. Radiat Res 184:249–258. doi: 10.1667/RR14092.1 CrossRefGoogle Scholar
- Marcantonio P, Del Re B, Franceschini A, Capri M, Lukas S, Bersani F, Giorgi G (2010) Synergic effect of retinoic acid and extremely low frequency magnetic field exposure on human neuroblastoma cell line BE(2)C. Bioelectromagnetics 31:425–433Google Scholar
- Nüsgen N, Goering W, Dauksa A, Biswas A, Jamil MA, Dimitriou I, Sharma A, Singer H, Fimmers R, Fröhlich H, Oldenburg J, Gulbinas A, Schulz WA, El-Maarri O (2015) Inter-locus as well as intra-locus heterogeneity in LINE-1 promoter methylation in common human cancers suggests selective demethylation pressure at specific CpGs. Clin Epigenetics 7:17. doi: 10.1186/s13148-015-0051-y CrossRefGoogle Scholar
- O’Hagan HM, Wang W, Sen S, Destefano Shields C, Lee SS, Zhang YW, Clements EG, Cai Y, Van Neste L, Easwaran H, Casero RA, Sears CL, Baylin SB (2011) Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands. Cancer Cell 20:606–619. doi: 10.1016/j.ccr.2011.09.012 CrossRefGoogle Scholar
- Schulz WA (2006) L1 retrotransposons in human cancers. J Biomed Biotechnol 2006(1):83672Google Scholar
- Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P, Thomsen C, Wright J, Athersuch TJ, Avellana N, Basagaña X, Brochot C, Bucchini L, Bustamante M, Carracedo A, Casas M, Estivill X, Fairley L, van Gent D, Gonzalez JR, Granum B, Gražulevičienė R, Gutzkow KB, Julvez J, Keun HC, Kogevinas M, McEachan RR, Meltzer HM, Sabidó E, Schwarze PE, Siroux V, Sunyer J, Want EJ, Zeman F, Nieuwenhuijsen MJ (2014) The human early-life exposome (HELIX): project rationale and design. Environ Health Perspect 122(6):535–544Google Scholar