Low-frequency electromagnetic fields induce premature terminal differentiation of in-vitro cultured human skin and lung fibroblasts

Abstract

In order to investigate the effects of low-frequency electromagnetic fields on the differentiation process of cultured fibroblasts, human skin (cell strain HH-8) and lung fibroblasts (cell strain WI-38) as well as SV40-transformed human lung fibroblasts (cell line WI-38/SV40) were exposed (2 × 6 h per day) to biphasic electromagnetic fields (EMF; 20 Hz, 6 mT) for up to 21 days. As analysed by cell biological (cell type frequencies), biochemical (collagen synthesis) and molecular markers (expression of protein PIVa), both human skin and lung fibroblasts were induced to differentiate prematurely into irreversible postmitotic cells of the terminal cell type PMFVI within 1–2 cell division cycles. EMF-induced PMFVI-type fibroblasts are characterized by the same morphological, biochemical and molecular markers as spontaneously arising PMF-type cells. Prematurely arising EMF-induced PMFVI-type cells showed a 10–13 fold enhanced synthesis of total collagen; PMFVI-specific changes in the content of interstitial collagen types I, III and V; as well as the PMFVI-cell type specific expression of protein markers of terminal differentiation, especially protein PIVa. EMF exposure of SV40-transformed human lung fibroblasts (cell line WI-38/SV40) resulted in the terminal differentiation into postmitotic cell types of approximately only two-thirds of the cells. One-third of the SV40-transformed human lung fibroblasts were insensitive to EMF. Like untransformed control cells (WI-38), the EMF-induced post-mitotic WI-38/SV40 cells showed enhanced total collagen synthesis. These results indicate that exposure of human skin and lung fibroblasts to low-frequency electromagnetic fields in vitro induces prematurely the differentiation into terminally differentiated postmitotic cells, which when occurring spontaneously seems to involve the repression of proto-oncogene c-fos.