Magnetic fields (MF) of 50 Hz at 1.2 μT as well as 100 μT cause uncoupling of inhibitory pathways of adenylyl cyclase mediated by melatonin 1a receptor in MF-sensitive MCF-7 cells

Magnetic fields (MF) of 60 Hz at 1.2 muT were previously shown to inhibit the antiproliferative effect of melatonin on MCF-7 cells (Liburdy,R.P., 1993, J. Pimeal Res. 14, 89-97), In addition, three laboratories (Blackman,C.F. and Benane,S,G,, 1998; Luben,R,A, and Morgan,A.P., 1998; Morris,J.E., Chrisler,W.B., Miller,D.L., Sasser,L,B, and Anderson,L,E,, 1998; 20th Annual Meeting of the Bioelectromagnetics Society, At. Pete Beach, FL) independently reported results consistent with this finding. In this study, we investigated the molecular basis of the biological effects of MF using MCF-7 cells. Only la melatonin receptors were identified by the [I-125]melatonin binding assay and RT-PCR analysis. Moreover, preceding exposures to MF of 100 muT for 3, 5 and 7 days blocked the melatonin-induced inhibition of cAMP accumulation in a time-dependent manner, while none of the melatonin receptor functions or GTPase and adenylyl cyclase activities were affected. Estrogen-evoked cell proliferation was not altered by MF either. Exposure to 1.2 muT MF exerted the same effects on the melatonin-signaling pathway as that to 100 muT. Thus, this is the first study to provide evidence that R;IF may cause uncoupling of signal transduction from melatonin receptors to adenylyl cyclase.