Influence of 50 Hz electromagnetic fields in combination with a tumour promoting phorbol ester on protein kinase C and cell cycle in human cells

It still is an unsolved issue whether exposure to power-line frequency electromagnetic fields (EMF) may promote carcinogenesis and if so whether it does so by influencing the proliferation, the survival, and the differentiation of cells. Since the family of protein kinases C (PKC) takes part in these processes by interacting with signal transduction pathways at several levels including the activation of transcription factors, we evaluated in the present study the effects of exposure of human amniotic fluid cells (AFC) to 50Hz, 1 mT electromagnetic fields (EMF) alone and in combination with the tumour promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) on the subcellular localization of PKC protein, on PKC enzyme activity, and on the cell cycle distribution. Quantitative analyses of the PKC expression pattern demonstrated the translocation of PKC from the cytosolic to the membrane fraction after exposure to 10, 50, 100nM, and 1 muM TPA. EMF exposure alone showed no effect on PKC translocation. Co-exposure to 10, 50, and 100nM TPA and 1 mT EMF revealed a significant additive effect (25 +/- 50, 66 +/- 29, 22 +/- 50%, respectively) with the most prominent increase at the concentration of 50nM TPA. At the highest concentration of TPA used (1 muM) no additive effect of EMF could be observed. Data on enzymatic activity indicate that EMF modulate the PKC activity, showing a significant increase of 10 +/- 16% in total PKC activity after co-exposure to 50nM TPA and 1 mT EMF when compared to 50nM TPA alone. Flow cytometric analyses showed a transient cell cycle arrest in G(0)/G(1)-phase followed by a delayed transit through S-phase in response to TPA, which was, however, not enhanced by co-exposure with EMF. We conclude that in AFC cells TPA at lower concentrations (less than or equal to 100nM) induces a less than maximum effect on the PKC pathway, which can be enhanced by the applied EMF.