Interaction of BCG-Activated Macrophages With Neoplastic and Nonneoplastic Cell Lines in Vitro: Quantitation of the Cytotoxic Reaction by Release of Tritiated Thymidine From Prelabeled Target Cells

Abstract

Peritoneal cells from mice infected ip with Mycobacterium bovis, strain BCG, were cytotoxic to syngeneic tumor cells in vitro. Cytotoxicity was estimated by measurement of release of tritiated-thymidine (³H-TDR) from prelabeled target cells. The cell responsible for tumor cytotoxicity was the macrophage. Macrophages from uninfected mice or from oil-, starch-, or thioglycollateinduced peritoneal exudates had little effect on labeled tumor monolayers. Tumoricidal macrophages were present at 3–7 days and persisted through 6 weeks after a single BCG injection. Two neoplastic/nonneoplastic cell-line pairs, all four of the cell lines derived from a cloned syngeneic embryo cell line, were used as target cells for BCG-activated macrophages. Both tumor cell lines released significantly more ³H-TDR than did the two nonneoplastic lines. In a mixed neoplastic/nonneoplastic target cell population, BCG-activated macrophages selectively destroyed the neoplastic cells; nonneoplastic cells were not affected as “innocent bystanders”.