MACROPHAGE CYTOTOXICITY AGAINST MURINE METH-A SARCOMA INVOLVES NITRICOXIDE-MEDIATED APOPTOSIS

We have studied the cytotoxic effect of stimulated macrophages on Meth A tumor cells in vitro. When stimulated with interferon-gamma and sol uble beta-1,3-D-glucan, macrophages exerted cytotoxicity towards synge neic Meth A tumor cells. This cytotoxicity was associated with a high level of nitric oxide production. Both cell death and nitric oxide pro duction were significantly inhibited by the addition of aminoguanidine , a specific inhibitor of inducible nitric oxide synthase (iNOS), to t he culture medium. The cytotoxic effect was accompanied by internucleo somal cleavage of DNA as shown by electrophoresis and DNA fragmentatio n assay. (C) 1996 Academic Press, Inc.