RESUMO
Exposure to 60 Hz magnetic fields (MFs) may be a risk factor for human cancer. One mechanism through which MFs could influence neoplastic development is through alterations in the expression of cancer-related genes. Previous molecular studies of the action of MFs have measured effects on a limited number of genes. In the present studies, arrays containing cDNAs for 588 cancer-related genes were used to approach the hypothesis that the biological activity of MFs is mediated by alterations in gene expression. Cultures of normal (HME) and transformed (HBL-100) human mammary epithelial cells and human promyelocytic leukemia (HL60) cells were exposed to MFs at field strengths of 0, 0.01 or 1.0 mT for 24 h. Several genes were identified in MF-exposed cells whose expression was increased by at least twofold or decreased by 50% or more. However, no gene was found to be differentially expressed in each of three independent exposures for any cell type, and no relationship between exposure intensity and differential gene expression was found. These studies failed to identify a plausible genetic target for the action of MFs in human cells, and they provide no support for the hypothesis that MF exposure alters the expression of genes that are involved in cancer development.
Assuntos
Campos Eletromagnéticos/efeitos adversos , Regulação Leucêmica da Expressão Gênica/efeitos da radiação , Expressão Gênica/efeitos da radiação , Oncogenes/efeitos da radiação , Mama/citologia , Mama/efeitos dos fármacos , Mama/metabolismo , Mama/efeitos da radiação , Linhagem Celular , Linhagem Celular Transformada , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação para Baixo/efeitos da radiação , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Feminino , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Oncogenes/genética , Reprodutibilidade dos Testes , Acetato de Tetradecanoilforbol/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Regulação para Cima/efeitos da radiaçãoRESUMO
Epidemiological data suggest that exposure to power-frequency (50/60 Hz) magnetic fields (MFs) may be a risk factor for breast cancer in humans. To determine whether MFs affect human breast cancer cells, we measured viability, growth and cytotoxicity in a battery of breast cancer cell lines after in vitro MF and sham exposure. Cells of three estrogen receptor-positive human breast cancer cell lines (MCF-7, ZR-75-1 and T-47D) and one estrogen receptor-negative human breast cancer cell line (MDA-MB-231) and normal (nontransformed) human breast epithelial cells were exposed to MFs (1 mT) or sham fields (<0.0001 mT) for 72 h. Cell viability was determined using the sulforhodamine B (SRB) assay at 0 and 72 h after the MF exposure period. Cell growth was measured as the change in SRB dye uptake over 72 h after MF exposure. MF exposure had no effect on cell viability or growth in any cell type examined. Similarly, MF exposure had no effect on cytotoxicity induced by exposure to the retinoid N-(4-hydroxyphenyl)retinamide. These data do not support the hypothesis that MF exposure stimulates growth of breast cancer cells.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Mama/efeitos da radiação , Campos Eletromagnéticos , Células Epiteliais/efeitos da radiação , Apoptose , Mama/citologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Células Epiteliais/citologia , Feminino , Fenretinida/farmacologia , Humanos , Receptores de Estrogênio/metabolismo , Rodaminas/farmacocinética , Células Tumorais CultivadasRESUMO
Epidemiology suggests a possible relationship between exposure to power frequency magnetic fields (EMF) and breast cancer. One mechanism through which EMF could stimulate breast cancer induction is via altered expression of oncogenes and/or tumor suppressor genes that regulate normal and neoplastic growth. To evaluate the hypothesis that EMF action in the breast is mediated by alterations in gene expression, transcript levels of c-myc and a battery of other cancer-associated genes were quantitated in human breast epithelial cells exposed to pure, linearly polarized 60 Hz EMF with low harmonic distortion. HBL-100 cells and normal (non-transformed) human mammary epithelial cells were exposed to EMF flux densities of 0.1, 1.0 and 10.0 Gauss (G) for periods ranging from 20 min to 24 h; concurrent sham controls were exposed to ambient fields (<0.001 G) only. Gene expression was quantitated using ribonuclease protection assays. EMF exposure had no statistically significant effect on basal levels of c-myc transcripts in either human breast cell model, and had no effect on alterations in c-myc expression induced by 12-O-tetradecanoylphorbol-13-acetate. Transcript levels of c-erbB-2, p53, p21, GADD45, bax, bcl-x, mcl-1, and c-fos were also unaffected by EMF exposure. These results suggest that EMF is unlikely to influence breast cancer induction through a mechanism involving altered expression of these genes.