CYTOSTATIC ELIMINATION OF SYNGENEIC RAT TUMOR CELLS IN VITRO BY NONSPECIFICALLY ACTIVATED MACROPHAGES

Syngeneic tumor cell lines induced in inbred DA rats by polyoma virus, dimethylbenzanthracene, or methylcholanthrene were interacted in vitro with syngeneic effector cells. Glycogen-induced peritoneal exudate cells, predominantly polymorphonuclear leukocytes, and proteose peptone-induced peritoneal cells, principally macrophages, were the effector cells employed. Activated, nonimmune macrophages or exudative polymorphonuclear leukocytes produced pronounced morphological changes in syngeneic tumor cells as evidenced by a substantial reduction in tumor cell numbers and appearance of shrunken cells, even though there was no increase in cell debris. Polymorphonuclear leukocytes exerted a generally similar but quantitatively much diminished effect. These effector cells constantly produced a decrease in the incorporation by tumor cells of DNA precursors such as [(3)H]thymidine and of RNA precursors such as [(3)H]uridine. In this regard, the effector cells were quite refractory to high doses of X-irradiation. Interaction of target cells with activated, nonimmune macrophages yielded low but consistent signs of cytotoxicity, whereas polymorphonuclear leukocytes gave no such effects. Elimination of functional macrophages by silica, an agent specifically toxic for macrophages, resulted in unrestricted tumor cell proliferation despite continued generation of cytotoxicity. Accordingly, cytostatic mechanisms appear to play a predominant role in the elimination of tumor cells by nonimmune phagocytes. Evidence from a variety of experimental approaches suggest that the cytostatic effect is dependent on cell-to-cell contact.