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Morphologic and Synthetic Response of Normal and Tumor Muscle Cultures to Nickel Sulfide¹

Department of Anatomy, Ontario Veterinary College, University of Guelph, Guelph, Canada

An investigation was undertaken to study the morphologic and synthetic response of normal and tumor muscle cultures to nickel sulfide. The normal muscle cultures were derived from embryonic muscle tissues, and tumor muscle cultures were initiated from Ni₃S₂-induced rhabdomyosarcomas. The morphologic features and pattern of DNA synthesis of the fibroblast-like cells were greatly affected when embryonic muscle cultures under 72 hr old were exposed to Ni₃S₂, whereas older cultures containing differentiating muscle cells were less severely affected. In contrast, the Ni₃S₂-induced rhabdomyosarcoma cultures were apparently unaffected in their morphology and DNA synthetic patterin in response to Ni₃S₂ added to the medium. These observations indicate that Ni₃S₂ affects the "normal" mitotic cells either by interference with the cell membrane, intracellular enzyme systems, and/or the nucleic acids, while the differentiating muscle cells are resistant to the toxic action of Ni₃S₂. While prolonged exposure to Ni₃S₂ drastically reduces the percentage of "normal" cells entering S phase, it is noted that a small proportion of cells is capable of DNA synthesis. The presence of the few S phase cells in Ni₃S₂-treated embryonic musclecultures and the apparent resistance of Ni₃S₂-induced rhabdomyosarcoma cultures to Ni₃S₂ seem to suggest that the induction of Ni₃S₂ tumor in vivo involves the clonal proliferation of a few nickel-resistant cells.

¹ This investigation was supported in part by a grant-in-aid of research from the National Cancer Institute of Canada.

Received 10/10/66. Accepted 2/16/67.