DNA synthesis in heterokaryons of mouse peritoneal macrophages and various proliferating cultured cells was analyzed. Macrophages did not inhibit replication in the nuclei of non-immortalized and spontaneously immortalized cells (rat fibroblasts and macrophages, mouse pre-macrophages, NIH3T3 cells). On the contrary, the percentage of DNA-synthesizing nuclei of malignant HeLa cells was drastically reduced in heterokaryons. The transformation of NIH3T3 cells with c-Ki-ras oncogene and that of rat chondrocytes with p53 oncogene made these cells sensitive to the replication-inhibiting activity of macrophages in heterokaryons. Our observation represents a kind of "intracellular" cytotoxic activity of macrophages directed against transformed cells.
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