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Differentiation and Control of Mitosis in a Skeletal Muscle Tumor¹

Laboratory of Skeletal Muscle Research, Armed Forces Institute of Pathology, Washington, D. C. 20305 [M. A. N., M. R., J. L. M.], and Laboratory of Biology, National Cancer Institute, Bethesda, Maryland 20014 [P. A.]

A spontaneous tumor in a BALB/cAnN mouse contained two cell types: multinucleated, cross-striated skeletal muscle fibers and mononucleated, nonstriated cells. Mitotic figures were observed only in mononucleated cells and never in multinucleated units. The tumor was transplanted subcutaneously or intraperitoneally 5 times at 2- to 3-month intervals. It continued to form muscle fibers and its histological appearance did not change. In vitro, mononucleated cells liberated from the tumor incorporated thymidine-³H and proliferated. Multinucleated myotubes arose from the mononucleated cells, and nuclei in these myotubes were diploid and did not incorporate thymidine-³H. Mitoses in vitro were observed only in mononucleated cells. It is concluded that (a) muscle differentiation in the tumor occurs by the same processes which operate in normal myogenesis; (b) nuclei in mononucleated tumor cells have lost the ability to respond to environmental factors which suppress division in normal myogenic cells; (c) tumor myotube nuclei derived from mononucleated cells retain the capacity to respond to intracellular factors which suppress DNA synthesis and mitosis in normal fibers.

¹ This study was supported in part by Research Contract 3A-61102B71R-02 from the Medical Research and Development Command, U. S. Army, Washington, D. C.

² Recipient of USPHS International Postdoctoral Research Fellowship F05-TW-1169.02.

Received 5/ 5/69. Accepted 7/18/69.