Cytolytic activity of interferon-gamma and its synergism with 5-fluorouracil.
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 micrograms/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.
D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000302:isolation & purification / Q000494:pharmacology*; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D009369:Neoplasms / Q000276:immunology
D000911:Antibodies, Monoclonal; D008937:Mitomycins; D016685:Mitomycin; D007371:Interferon-gamma; D005472:Fluorouracil