title: Assessment of the neurotoxic potential of exposure to 50Hz extremely low frequency electromagnetic fields (ELF-EMF) in naïve and chemically stressed PC12 cells.
abstract: Increasing exposure to extremely low frequency electromagnetic fields (ELF-EMF), generated by power lines and electric appliances, raises concern about potential adverse health effects of ELF-EMF. The central nervous system is expected to be particularly vulnerable to ELF-EMF as its function strongly depends on electrical excitability. We therefore investigated effects of acute (30min) and sub-chronic (48h) exposure to 50Hz ELF-EMF on naïve and chemically stressed pheochromocytoma (PC12) cells. The latter have higher levels of iron and/or reactive oxygen species (ROS) and display increased vulnerability to environmental insults. Effects of ELF-EMF on Ca(2+)-homeostasis, ROS production and membrane integrity were assessed using Fura-2 single cell fluorescence microscopy, H2-DCFDA and CFDA assays, respectively. Our data demonstrate that acute exposure of naïve PC12 cells to 50Hz ELF-EMF up to 1000μT fails to affect basal or depolarization-evoked [Ca(2+)]i. Moreover, sub-chronic ELF-EMF exposure up to 1000μT has no consistent effects on Ca(2+)-homeostasis in naïve PC12 cells and does not affect ROS production and membrane integrity. Notably, in chemically stressed PC12 cells both acute and sub-chronic ELF-EMF exposure also failed to exert consistent effects on Ca(2+)-homeostasis, ROS production and membrane integrity. Our combined findings thus indicate that exposure to 50Hz ELF-EMF up to 1000μT, i.e. 10,000 times above background exposure, does not induce neurotoxic effects in vitro, neither in naïve nor in chemically stressed PC12 cells. Though our data require confirmation, e.g. in developing neuronal cells in vitro or (developing) animals, it appears that the neurotoxic risk of ELF-EMF exposure is limited.
authors.affiliation: Neurotoxicology Research Group, Toxicology Division, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, NL 3508 TD Utrecht, The Netherlands. Electronic address: m.w.g.d.m.degroot@uu.nl.
authors.forename: Martje W G D M
authors.initials: MW
authors.lastname: de Groot
authors.affiliation: Neurotoxicology Research Group, Toxicology Division, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, NL 3508 TD Utrecht, The Netherlands. Electronic address: m.d.m.kock@uu.nl.
authors.forename: Marjolijn D M
authors.initials: MD
authors.lastname: Kock
authors.affiliation: Neurotoxicology Research Group, Toxicology Division, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, NL 3508 TD Utrecht, The Netherlands. Electronic address: r.westerink@uu.nl.
authors.forename: Remco H S
authors.initials: RH
authors.lastname: Westerink
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004574:Electromagnetic Fields; D007501:Iron / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000633:toxicity*; D013312:Stress, Physiological
chemical_list: D017382:Reactive Oxygen Species; D007501:Iron; D002118:Calcium
keywords: Chemically stressed PC12 cells; Extremely low frequency electromagnetic fields (ELF-EMF); In vitro neurotoxicity; Intracellular [Ca(2+)](i); Oxidative stress; Single cell fluorescence calcium-imaging