ELECTROMAGNETIC-FIELD INDUCED CHANGES IN LIPID 2ND MESSENGERS

Initial studies with a human hematopoietic cell line, TF-1, suggest mu ltifarious effects of electromagnetic fields on lipid signal transduct ion, We have examined the effects of pulsed magnetic fields (2 T, 84 m u s zero-to-peak haversine, 91 V/m induced electric field) on the cell cycle by flow cytometry. A 31% increase of cells in the G1 phase occu rred concurrently with a 35% decrease of cells in S-phase, which sugge sts that doses of 30 or 40 pulses have an anti-proliferative effect. C hanges in the lipid second messengers, diacylglycerol (DAG) and phosph atidic acid (PA) with stimuli of 2 T intensity were also dependent on the number of pulses. DAG production doubled with 30 pulses and triple d with 30 pulses, and PA levels were reduced to one third and one tent h of the original levels, Phospholipase D (PLD) up-regulation was asse ssed directly by the capacity of PLD to catalyze transphosphatidylatio n in the presence of alcohol, [H-3]Phosphatidylethanol formed rapidly and continued to increase with concomitant decreases in [H-3]PA and pa rallel generation of [H-3]DAG. Propranolol, an inhibitor of PA phospho hydrolase, inhibited the formation of DAG in a dose-dependent manner w ith a marked increase in PA production. Examination of the kinetics of formation of [H-3]choline and [H-3]phosphocholine at different times after stimulation showed a rapid and consistent increase in [H-3]choli ne, whereas [H-3]phosphocholine increase was evident only 60 min after stimulation, Magnetic exposure also caused a shift in some molecular species patterns of DAG and PA which could be correlated with phosphat idylinositol, phosphatidylethanolamine and phosphatidylcholine molecul ar species decreases, Therefore, we propose that the PC-PLC pathway ma y be temporarily inactivated for short period of time by exposure to p ulsed stimuli, and the PC-PLD pathway is up-regulated based on: (1) ce llular release of [H-3]choline; (2) rapid intracellular formation of [ H-3]PA followed by [H-3]DAG; (3)active transphosphatidylation; and (4) blockade of DAG formation by propranolol.