Increased lymphocyte-mediated destruction of tumor cells in microcytotoxicity assays seen after addition of inhibitors of protein synthesis

Abstract

Two methylcholanthrene (MCA)-induced sarcomas were used as targets in a criss-cross pattern to study lymph-node-cell (LNC)-mediated cytotoxic reactions to tumor-specific antigens in a 26 h microcytotoxicity assay. Destruction of plated tumor cells by syngeneic LNC from specifically tumor-immune or multiparous mice significantly increased when cycloheximide was added during the whole duration of the test. A similar increase was also seen if either cycloheximide or puromycin was added during the last 6 h of the 24 h assay. A slight increase of cytotoxicity was seen if, instead, the mixture of fetal calf serum and LNC was simply replaced by serum-free medium during the last 6 h of the test. The findings suggest that a repair process may occur in target cells contacted by immune LNC or that target cells damaged by contact with immune LNC are more sensitive to further damage by the exposure to certain inhibitors of protein synthesis. Additional mechanisms may contribute to the increased LNC-mediated cytotoxicity seen when cycloheximide is added for the whole duration of the test.