Anti-tumour cytotoxin produced by human monocytes: studies on its mode of action

Human monocytes can be induced to synthesize a cytotoxin which affects certain tumour cell lines. The interaction of monocyte cytotoxin with a susceptible cell line (L929) has been studied to obtain clues to the mode of action of the cytotoxin. The cytotoxin acts directly on the cells rather than on the culture medium and is cytotoxic at higher concentrations and cytostatic at lower concentrations. First signs of cell damage appear about 20 h after contact with the cytotoxin which must be present throughout this period. The cytotoxin probably acts on the cell surface and is more effective at 40 degrees C than at 37 degrees C. For a given amount of cytotoxin the effects are inversely proportional to the target cell concentration. Treatment of the cytotoxin with phenanthroline inhibits cytotoxicity while treatment of the target cells with actinomycin D, but not cycloheximide or puromycin, enhances cytotoxicity. After 24 h cytotoxin treatment the target cells exhibit reduced respiration rate but enhanced glycolysis and glucose uptake suggesting mitochondrial dysfunction. A possible interpretation of these data is that the monocyte cytotoxin is a metalloenzyme which inactivates a cell surface receptor for a nutrient essential for mitochondrial function.