EFFECTS AND MECHANISMS OF EMF SIGNAL TRANSDUCTION

DESCRIPTION: The goal of this proposal is to substantiate certain
reported effects of weak, 60 Hz electromagnetic fields on cell
functions, and to define a cellular mechanism for the effects. The
proposed work begins with an attempt to reproduce c-myc proto-oncogenes
in CEM-CM3 T-lymphoblastoid cells. A magnetic field exposure system with
identical sham set-up will be built to duplicate the setting. After the
further experiments employing 60 Hz electric fields of 2-200 Mv/m alone,
(corresponding to about 3-300 mA/m(2) of current density in the culture
medium), or in addition to magnetic field and its induced current, will
be performed. To amplify the electromagnetic field effect on
carcinogenesis, a two-stage carcinogenesis model system, i.e., the
methylcholanthrene-initiated, retinoid suppressed C3H/10T(1/2)
fibroblasts, will be used to test the hypothesis that electromagnetic
field acts as a promoter rather than as an initiator. The timing and
the extent of expression of the transformed phenotype, proto-oncogene
expression, and proliferation of initiated cells will be
determined.Electromagnetic field-induced calcium signals in these cells
and in lymphoblastoid cells will be measured and related to protein
kinase C activation and other downstream functions, to test the
hypothesis that electromagnetic field-induced calcium influx is a primary
or secondary messenger in transducing signals related to carcinogenic
promotion. The origin and mechanism of inducing calcium signals by
electromagnetic field will be investigated, by using channel blockers,
calmodulin inhibitors, and calcium pump modulators, and by matching the
response frequency windows with hypothetical resonance amplification by
intra-, extra-, and trans-membrane circuits. The outcome is expected to
explain, and to define the significance limits of biological effects of
weak electromagnetic field corresponding to environmental exposures.