Extremely low frequency electromagnetic field exposure promotes differentiation of pituitary corticotrope‐derived AtT20 D16V cells

Abstract

The pituitary corticotrope-derived AtT20 D16V cell line responds to nerve growth factor (NGF) by extending neurite-like processes and differentiating into neurosecretory-like cells. The aim of this work is the study of the effect of extremely low frequency electromagnetic fields (ELF-EMF) at a frequency of 50 Hz on these differentiation activities. To establish whether exposure to the field could influence the molecular biology of the cells, they were exposed to a magnetic flux density of 2 milli-Tesla (mT). Intracellular calcium ([Ca2+]i) and intracellular pH (pHi) were monitored in single exposed AtT20 D16V cells using fluorophores Indo-1 and SNARF for [Ca2+]i and pHi, respectively. Single-cell fluorescence microscopy showed a statistically significant increase in [Ca2+]i followed by a drop in pHi in exposed cells. Both scanning electron microscopy (SEM) and transmission microscopy of exposed AtT20 D16V cells show morphological changes in plasma membrane compared to non-exposed cells; this modification was accompanied by a rearrangement in actin filament distribution and the emergence of properties typical of peptidergic neuronal cells-the appearance of secretory-like granules in the cytosol and the increase of synaptophysin in synaptic vesicles, changes typical of neurosecretory-like cells. Using a monoclonal antibody toward the neurofilament protein NF-200 gave additional evidence that exposed cells were in an early stage of differentiation compared to control. Pre-treatment with 0.3 microM nifedipine, which specifically blocks L-type Ca2+ channels, prevented NF-200 expression in AtT20 D16V exposed cells. The above findings demonstrate that exposure to 50 Hz ELF-EMF is responsible for the premature differentiation in AtT20 D 16 V cells.

Effects of Fifty-Hertz Electromagnetic Fields on Granulocytic Differentiation of ATRA-Treated Acute Promyelocytic Leukemia NB4 Cells

“…The exposure to extremely low frequency ELF-EMF (50 Hz) induced more rapid maturation and differentiation in neural cells. These included rat immature cerebellar granule neurons and mouse embryonic neural stem cells [3, 41], as well as mouse pituitary corticotrope-derived cells [42]. Similar results were obtained in human cardiac stem cells derived from human myocardial bioptic specimens, where differentiation toward a cardiac-specific phenotype was observed after exposure to low-frequency EMF [43].…”

Molecular basis underlying the biological effects elicited by extremely low-frequency magnetic field (ELF-MF) on neuroblastoma cells

“…Several studies suggested that there is a possible association between ELF-MFs and malignancies in childhood and adulthood such as leukemia and nervous system tumors as well as cardiovascular and neurological disorders [Wertheimer and Leeper, 1979;IARC, 2002;Håkansson et al, 2003;Draper et al, 2005;Davanipour et al, 2007]. A number of in vivo and in vitro investigations have shown a possible co-promoter capacity of ELF-MFs on tumor growth as well as the potential effects elicited by ELF-MFs on various cellular functions [Crumpton and Collins, 2004;Simkó , 2004;Santini et al, 2005;Wolf et al, 2005;Berg and Berg, 2006;Frahm et al, 2006;Lisi et al, 2006;Palumbo et al, 2006;Gottwald et al, 2007]. Unfortunately, the biological mechanisms by which these physical agents can be involved in a possible tumor-promoting or tumor-initiating action are still unclear.…”

Effect of ELF-EMF on antioxidant status and micronuclei in K562 cells and normal lymphocytes

“…Some of them report stimulatory [26], some inhibitory effects [6,27] and some studies even showed the absence of effect on cell cycle distribution [22]. Lisi et al considered that ELF-EMF exposure not only triggers a metabolic cellular response able to assure good survival to cells, but also has a differentiating potential, since they induce significant increase in the levels of the differentiation markers growth-associated protein-43 (GAP-43) and neuronspecific enolase (NSE) [28]. Crumpton et al pointed out that the ELF-EMF could influenze cell proliferation and DNA damage through the action of free radicals in both normal and tumor cells [3].…”