Abstract B32: Effects of 120 Hz electromagnetic fields on the early hepatocarcinogenesis in F-344 rats
Authors: Mónica Noemí Jiménez-García, Jaime Arellanes-Robledo, Miguel Ångel Rodríguez-Segura, Diana Ivette Aparicio-Bautista, Saúl Villa-Treviño, Juan José Godina-Nava
Journal: Cancer Research (2009)

Abstract Background: In recent years the extremely low frequency of electromagnetic fields (ELF-EMF) has been studied with major interest due their possible effects on the human health. Researches about that are contrasting; whereas some authors associate to ELF-EMF exposure with carcinogenesis, studies in experimental models and human being cancer have shown that the ELF-EMF not increases the risk of several cancer types. Previously, a biophysical model has hypothesized that the action mechanism of ELF-EMF on cells is through forced-vibration of the free ions that exist on all plasma membranes and that can move across of them using transmembrane proteins, disordering the electrochemical balance of the plasma membrane and therefore the whole cell function. In this way, cancer development takes place through rapid proliferation and the continuous increase of altered cells modifying the cellular environment including the flow of ionic charges across the cell membrane; considering that hepatocellular carcinoma (HCC) is a common form of cancer and its incidence remains high; in this study we evaluated the effect of 4.5 mT-120 Hz electromagnetic field (EMF) on the development of preneoplastic lesions in experimental hepatocarcinogenesis. Methods: Male Fischer-344 rats were subjected to the modified hepatocyte resistant model and were exposed to uniform and homogenous EMF of 4.5 mT-120 Hz during 50 min per day since seven days before until 25 days after carcinogenesis initiation when animals were sacrificed. The effect of ELF-EMF on early hepatocarcinogenesis, the induction of altered cells death and proliferation, and cell cycle progression was evaluated by histochemical, TUNEL assay, caspasa 3 level, immunohistochemical and western blot analysis. Results: The application of 4.5 mT-120 Hz EMF compared with shamexposed group, decreased over 50% the number and area of γ-glutamyl transpeptidase-positive preneoplastic lesions and the glutathione S-transferase placental expression (P=0.008 and P=0.03, respectively), both markers that identify preneoplastic lesions. Cells TUNEL positive and cleaved caspase 3 levels were unaffected; however, the cell number/mm2 in serial liver tissues of proliferating cell nuclear antigen (PCNA), Ki-67 and cyclin D1 expression decreased significantly (&amp;gt;80%) becoming similar to normal control (P=0.03, P=0.004 and P=0.008, respectively). Finally, western blot analysis revealed a diminution over 50% of PCNA and cyclin D1 expression (P=0.03 and P=0.01, respectively). Conclusion: The application of 4.5 mT-120 Hz EMF affect the early chemically induced carcinogenesis in rat liver through reduction of the proliferation markers such as PCNA and Ki-67 affecting the cyclin D1 expression which participates in the cell cycle continuity, without altering apoptosis process. These results suggest that ELF-EMF could be regulating the altered cellular homeostasis to inhibit the cancer development. Finally, this finding may be the base for clinical applications in the design of strategies to treat HCC. Citation Information: Cancer Res 2009;69(23 Suppl):B32.