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

Abstract

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 50 Hz, 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, 100 nM, and 1 microM TPA. EMF exposure alone showed no effect on PKC translocation. Co-exposure to 10, 50, and 100 nM TPA and I mT EMF revealed a significant additive effect (25 +/- 50, 66 +/- 29, 22 +/- 50%, respectively) with the most prominent increase at the concentration of 50 nM TPA. At the highest concentration of TPA used (1 microM) 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 50 nM TPA and 1 mT EMF when compared to 50 nM TPA alone. Flow cytometric analyses showed a transient cell cycle arrest in G0/G1-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 (< or = 100 nM) induces a less than maximum effect on the PKC pathway, which can be enhanced by the applied EMF.