We studied the effect of the estrogenic pesticide methoxychlor (MXC) on skeletal muscle development using C2C12 muscle cell culture. Various concentrations of MXC or beta-estradiol (E) were added to the culture media. MXC (100 microM) disrupted myoblast fusion into myotubes, but 10 microM MXC or 10 microM E had no effect. Correlated with the diminished size of the myotubes, the clustering of acetylcholine receptors (AChRs) was inhibited by 100 microM MXC, but not by 10 microM MXC or 10 microM E. However, since clusters of AChR receptors did form, the postsynaptic clustering mechanism remained intact. Since E did not disrupt myoblast fusion into myotubes or the clustering of AChRs, we conclude that the abnormality induced by MXC is mediated by a mechanism of action that is independent of E. We believe this to be the first demonstration that MXC induces abnormal effects in the process of muscle development in skeletal muscle cell culture.
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