EFFECTS OF 60-HZ FIELDS, ESTRADIOL AND XENOESTROGENS ON HUMAN BREAST-CANCER CELLS

If exposure to xenoestrogens or electromagnetic fields (EMFs) such as 60 Hz contributes to the etiology of breast cancer, it is likely that they must stimulate the growth of breast cells, damage genetic materia l or enhance the effects of other mitogenic or mutagenic agents (co-pr omotion). Therefore, the ability of xenoestrogens or exposure to 60-Hz fields to stimulate the entry of growth-arrested human breast cancer cells into the cell cycle was determined using cyclin-dependent kinase 2 (Cdk2) activity, synthesis of cyclin D1 and cdc2 activity. Exposure of estrogen receptor-positive MCF-7 or T-47D cells to estrogen and xe noestrogens (DDT and Red No. 3) increased Cdk2 and cyclin B1-cdc2 acti vity and cyclin D1 synthesis. Exposure of breast cancer cells to 12 mG or 1 or 9 G electromagnetic fields at 60 Hz failed to stimulate Cdk2 or cyclin B1-cdc2 activity or cyclin D1 synthesis. Simultaneous co-exp osure of cells to 60-Hz fields and chemical promoters did not enhance Cdk2 activation above the levels produced by the chemical promoter alo ne. Estrogen and xenoestrogens also stimulated binding of the estrogen receptor to the estrogen receptor element but the EMF did not. Phorbo l 12-myristate 13-acetate (PMA) induced phosphorylation of p53 and pRb 105 in MCF-7 cells, but EMF exposure had no effect. DNA-damaging chemo therapeutic agents and Red Dye No. 3 were found to increase p53 site-s pecific DNA binding in breast cancer cells, but EMF exposure did not. Differential display analysis failed to detect any effect of EMF expos ure on gene expression in MCF-7 cells, whereas the effects of estradio l were detected. These studies suggest that estrogen and xenoestrogens stimulate growth-arrested breast cancer cells to enter the growth cyc le, but EMF exposure does not. Site-specific p53-DNA binding was incre ased in MCF-7 cells treated with DNA-damaging agents, but not by EMF e xposure. EMF exposure does not appear to act as a promoter or DNA-dama ging agent for human breast cancer cells in vitro. (C) 1996 by Radiati on Research Society