Cytolytic activity of interferon‐gamma and its synergism with 5‐fluorouracil

Publisher Website
Google Scholar
Abstract
Highly purified natural or recombinant human immune interferon (IFN‐gamma) was found to be directly cytolytic to certain tumor cell lines in vitro. Out of 5 human tumor cell lines and one normal fibroblast line tested, the colon adenocarcinoma line HT‐29 and the rhabdomyosarcoma line A673 were highly sensitive to cytolysis by interferon, as determined by 125I‐iododeoxyuridine release in a 72 h microcytotoxicity assay. Cytolysis was marked at IFN‐gamma concentrations of less than I U/ml, and it reached a near‐maximal level at 6.4 U/ml. A synergistic cytolysis on HT‐29 cells of IFN‐gamma and 5‐fluorouracil (5‐FU) was observed at 5‐FU concentrations ranging from 64 to 640 μgl ml. In contrast, no synergism was observed between IFN‐gamma and mitomycin C. The direct cytolytic activity and synergistic cytolysis with 5‐FU of the IFN‐gamma preparations used in the present study were abolished completely by treatment with a neutralizing monoclonal antibody specific for human IFN‐gamma.