Toxic effects of polychlorinated biphenyls in myogenic cells

Polychlorinated biphenyls (PCBs) are molecules structurally related to dioxins and were widely used in the past in industrial applications. Their chemical stability and high lipophilicity make them persistent pollutants and dangerous occupational contaminants. Our previous results showed that "low concentrations" of PCBs ( 10 mu g/ml, using the commercial mixture Aroclor 1254) inhibit in vitro hormonal induced myogenic differentiation. Here we extend the notion of PCBs as inhibitors of myogenic differentiation induced by lower serum medium. Aroclor 1254 treatment of myogenic cells, induced to differentiate in low serum medium, inhibits (at concentrations 10 mu g/ml) the extent of fusion and the size of the myotubes as well as the accumulation of sarcomeric myosin. We also investigated whether the cell mortality observed at Aroclor 1254 concentrations 10 mu g/ml is due to necrosis or to apoptosis. Using different approaches, we observed that Aroclor 1254 causes necrosis but not apoptosis of myogenic cells in a dose-dependent manner. In addition, we report that Aroclor 1254 induces release of the intracellular enzymes lactate dehydrogenase (LDH) and creatine kinase (CK) in a dose-dependent manner. These results may explain the CK serum elevation observed in patients exposed to high doses of PCBs.