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 material or enhance the effects of other mitogenic or mutagenic agents (co-promotion). 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 xenoestrogens (DDT and Red No. 3) increased Cdk2 and cyclin B1-cdc2 activity 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-exposure of cells to 60-Hz fields and chemical promoters did not enhance Cdk2 activation above the levels produced by the chemical promoter alone. Estrogen and xenoestrogens also stimulated binding of the estrogen receptor to the estrogen receptor element but the EMF did not. Phorbol 12-myristate 13-acetate (PMA) induced phosphorylation of p53 and pRb1O5 in MCF-7 cells, but EMF exposure had no effect. DNA-damaging chemotherapeutic agents and Red Dye No. 3 were found to increase p53 site-specific DNA binding in breast cancer cells, but EMF exposure did not. Differential display analysis failed to detect any effect of EMF exposure on gene expression in MCF-7 cells, whereas the effects of estradiol were detected. These studies suggest that estrogen and xenoestrogens stimulate growth-arrested breast cancer cells to enter the growth cycle, but EMF exposure does not. Site-specific p53-DNA binding was increased in MC F-7 cells treated with DNA-damaging agents, but not by EMF exposure. EMF exposure does not appear to act as a promoter or DNA-damaging agent for human breast cancer cells in vitro.
Dees
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C
Health Sciences Research Division, Oak Ridge National Laboratory, Tennessee 37831-6109, USA.
Garrett
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S
Henley
D
D
Travis
C
C
D001483:Base Sequence; D001943:Breast Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D042846:CDC2-CDC28 Kinases; D002273:Carcinogens / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects; D004396:Coloring Agents / Q000633:toxicity; D019938:Cyclin D1; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D003634:DDT / Q000633:toxicity; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D004574:Electromagnetic Fields / Q000009:adverse effects*; D004958:Estradiol / Q000494:pharmacology*; D045166:Estradiol Congeners / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D004396:Coloring Agents; D016213:Cyclins; D017931:DNA Primers; D045166:Estradiol Congeners; D004968:Estrogens, Non-Steroidal; D015513:Oncogene Proteins; D011960:Receptors, Estrogen; D019938:Cyclin D1; D004958:Estradiol; D003634:DDT; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases