ERK1/2 phosphorylation, induced by electromagnetic fields, diminishes during neoplastic transformation

It has been suggested that electromagnetic (EM) fields can act as co-promot ers during neoplastic transformation. To examine this possibility, we studi ed the effects of 0.8-, 8-, 80-, and 300-mu T 60-Hz electromagnetic (EM) fi elds in INITC3H/10T1/2 mouse fibroblast cells. These cells are transformed carcinogenically by methylcholanthrene, but the neoplastic phenotype can be suppressed indefinitely by the presence of retinyl acetate (RAC) in the cu lture medium. The effects of EM field exposures were examined at three stag es: (1) before initiation of transformation (i.e., RAC in the culture media ); (2) early in the transformation process (4 days after withdrawal of RAG) ; and (3) at full of neoplastic transformation (10 days after withdrawal of RAG). EM field exposures induced significant increases in protein levels f or hsp70 and c-Fos and in AP-1 binding activity. EM fields induced phosphor ylation of MAPK/ERK1/2 before the onset of transformation, but these increa ses diminished during the transformation process. No phosphorylation in the other major extracellular stress pathway, SAPK/JNK, was detected in cells exposed to EM fields at any time before, during, or after neoplastic transf ormation. Human cells HL60, MCF7, and HTB124, exposed to EM fields, also sh owed MAPK/ERK1/2 phosphorylation. Cells treated with the phorbol ester, TPA , served as positive controls for AP-1 activation, c-Fos protein synthesis, and ERK1/2 phosphorylation. There was no indication that EM fields affecte d the rate of cell transformation or acted as a co-promoter, under the cond itions of this study. (C) 2000 Wiley-Liss, Inc.