Abnormal cytodifferentiation in leiomyosarcomas induced with injection of nickel subsulfide into skeletal muscles of rats. Light and electron microscopic observations.

Seven leiomyosarcomas, induced individually with a single injection of nickel subsulfide (0.4 mg) into skeletal muscles of Fisher 344 male rats were studied with the light and with the electron microscope. The tumors consisted of fibroblast-like cells lacking the cytoplasmic filaments found in normal maturing and mature smooth muscle, and of cells in which the appearance of these filaments occurred in the following sequence: first, actin filaments in concomitance with intermediate filaments; second, myosin filaments. According to work from several laboratories, normal embryonic smooth muscle was derived from fibroblast-like cells and a characteristic of their early differentiation was the appearance of filaments in a sequence similar to that in the present tumors. Similarities between normal and neoplastic muscle were also observed in the orientation of the filamentous components and in the changes in quantity occurring in them during the course of differentiation. However, in the neoplastic cells, nonfilamentous structures, such as gap junctions which normally increase in number with advancing cell maturation, were rarely detected. In addition, the sarcoplasmic reticulum was constantly far less developed than in the normal mature prototypes. The present observations suggest that the differentiation of the neoplastic cells in the early stages is similar to that under normal conditions of smooth muscle development, but it becomes abnormal in the advanced stages.